Rimonabant (SR141716)

For research use only.

Catalog No.S3021

4 publications

Rimonabant (SR141716) Chemical Structure

CAS No. 168273-06-1

Rimonabant (SR141716) is a selective antagonist of CB1 with IC50 of 13.6 nM and EC50 of 17.3 nM in hCB1 transfected HEK 293 membrane. Rimonabant is also a dual inhibitor of acyl CoA:cholesterol acyltransferases(ACAT) 1 and 2 and inhibits mycobacterial MmpL3.

Selleck's Rimonabant (SR141716) has been cited by 4 publications

Purity & Quality Control

Choose Selective Cannabinoid Receptor Inhibitors

Biological Activity

Description Rimonabant (SR141716) is a selective antagonist of CB1 with IC50 of 13.6 nM and EC50 of 17.3 nM in hCB1 transfected HEK 293 membrane. Rimonabant is also a dual inhibitor of acyl CoA:cholesterol acyltransferases(ACAT) 1 and 2 and inhibits mycobacterial MmpL3.
Features Efficacious to induce weight reduction and improvements in cardiometabolic risk factors, however was withdrawn in 2009 due to severe depressive disorder and anxiety.
Targets
ACAT1 [2]
()
ACAT2 [2]
()
MmpL3 [7]
()
hCB1 [1]
(Cell-free assay)
hCB2 [1]
(Cell-free assay)
13.6 nM 1.64 μM
In vitro

Rimonabant dose-dependently reduces ACAT activity in Raw264.7macrophages with IC50 of 2.9 μM and isolated peritoneal macrophages. Rimonabant inhibits ACATactivity in intact CHO-ACAT1 and CHO-ACAT2 cells and in cell-free assays with approximately equal efficiency with IC50 of 1.5 μM and 2.2 μM for CHO-ACAT1 and CHO-ACAT2, respectively. Consistent with ACAT inhibition, Rimonabant treatment blocks ACAT dependent processes in macrophages, oxysterol-induced apoptosis and acetylated-LDL induced foam cell formation. [2] Rimonabant antagonizes the inhibitory effects of cannabinoid receptor agonists on both mouse vas deferens contractions and adenylyl cyclase activity in rat brain membranes in a concentration-dependent manner. [3] Rimonabant significantly reduces cell growth and induces cell death of human colorectal cancer cells (DLD-1, CaCo-2 and SW620). Rimonabant is able to alter cell cycle distribution in all the cell lines tested. Particularly, Rimonabant produces a G2/M cell cycle arrest in DLD-1 cells without inducing apoptosis or necrosis. [4]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
CHO cells MYHGeY5kfGmxbjDhd5NigQ>? NYTxcHhQSWKrbHn0fUB1dyCmaYPwcIFk\SCdM1jdMXNTNSBzNEG3NVZCKGKrbnTpcochfG9iaIXtZY4hS0JzIILlZ4VxfG:{IHX4dJJme3OnZDDpckBEUE9iY3XscEBu\W2kcnHu[ZMtKEurPUiuPUBvVQ>? Mk[0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTB2NkW1OVIoRjFyNE[1OVUzRC:jPh?=
CHO M4PMUWZ2dmO2aX;uJIF{e2G7 NYHkfVc2SW62YXfvcol{fGmlIHHjeIl3cXS7IITve4Fz\HNiY3HucoFjcW6xaXSgdoVk\XC2b4KgNUBmgHC{ZYPz[YQh[XNiW{PIYWFz[WOqaXTvcolkKGGlaXSgdoVt\WG|ZTDpckBEUE9iY3XscJMtKEumPUCuNFAzPTF{zszN MV68ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yPDd|NkK0N{c,OTR5M{[yOFM9N2F-
CHO NEWxS29HfW6ldHnvckBie3OjeR?= MlTvSIl{eGyjY3Xt[Y51KG:oIFPQMVU2QTRyIHLpcoRqdmdiZoLvcUBz\WOxbXLpcoFvfCCqdX3hckBk[W6wYXLpco9q\CC{ZXPldJRweiBzIHX4dJJme3OnZDDpckBEUE9iY3XscJMtKEurPUCuNFI2|ryP MWS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yPDd|NkK0N{c,OTR5M{[yOFM9N2F-
CHO Mn7kSpVv[3Srb36gZZN{[Xl? NGqzW|ZC\m[rbnn0fUB1dyCmaYPwcIFk\SCFUD21OVk1OCCkaX7kbY5oKG[{b32gR4FvdmGkaX7vbYQhemWlZYD0c5IhOiCxZjDoeY1idiCneIDy[ZN{\WRiaX6gR2hQKGOnbHzzMEBMcT1zLkW4{txO NImxXpk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zNEezOlI1Oyd-MUS3N|YzPDN:L3G+
CHO MnnnSpVv[3Srb36gZZN{[Xl? NV3hUWQ1UW6qaXLpeI9zgSClb37j[Y51emG2aX;uJIFo[Wmwc4SgbJVu[W5icnXjc41jcW6jboSgZ4FvdmGkaX7vbYQhemWlZYD0c5IhfHmyZTCxJIV5eHKnc4Pl[EBqdiCFaHnu[ZNmKEijbYP0[ZIhV3[jcomgLGNJVyliY3XscJMtKEmFNUC9NE4xODcQvF2= NHzWSoc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zNUexN|QxOyd-MUW3NVM1ODN:L3G+
CHO NE\wT3VHfW6ldHnvckBie3OjeR?= NVi1NWh4UW5idnn0do8h[2GwbnHibY5wcWRicnXj[ZB1d3JiMTDhcpRi\2:waYPtJI9nKFt|SG3hdoFkcGmmb37pZ{Bi[2mmIILlcIVie2ViYomgR2hQKGOnbHzzMEBM\D1yLkCwNlUyOs7:TR?= NWrpRmFkRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUW3O|E1OjhpPkG1O|cyPDJ6PD;hQi=>
CHO NFfCe|RHfW6ldHnvckBie3OjeR?= MUDJckB3cXS{bzDkbZNxdGGlZX3lcpQhd2ZiQ2CtOVU6PDBiYnnu[Ilv\yC2bzDoeY1idiCFQkGgdoVk\XC2b4Kg[ZhxemW|c3XkJIlvKEOKTzDj[YxteyxiS3m9NE4xOjYQvF2= M3O4bFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF3N{exOFI5Lz5zNUe3NVQzQDxxYU6=
CHO NH\1fXZHfW6ldHnvckBie3OjeR?= NHy4TZhKdiC4aYTyc{BlcXOybHHj[Y1mdnRib3[gR3AuPTV7NECgZolv\GmwZzD0c{BpfW2jbjDDRlIhemWlZYD0c5Ih\XiycnXzd4VlKGmwIFPIU{Bk\WyuczygT4k:OS53ON88US=> NE\ITmE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zNUe3NVQzQCd-MUW3O|E1Ojh:L3G+
CHO M3rkd2Z2dmO2aX;uJIF{e2G7 MXjJcohq[mm2aX;uJI9nKFt|SG3TVk0yPDFuN{G2RUBjcW6maX7nJJRwKGi3bXHuJGNDOSC{ZXPldJRweiCneIDy[ZN{\WRiaX6gR2hQKGOnbHzzMEBMcT1yLkCwOVTPxE1? NWn2bWZyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUW4NFE5PDBpPkG1PFAyQDRyPD;hQi=>
CHO MlzJSpVv[3Srb36gZZN{[Xl? MnyyRY51[WexbnnzeIlkKGGldHn2bZR6KGGpYXnud5Qh[2GwbnHibY5wcWRicnXj[ZB1d3JiMTDt[YF{fXKnZDDifUBEWC13NUm0NEBqdmS3Y3XkJIFz[WOqbn;p[EBi[2mmIILlcIVie2ViaX6gR2hQKGOnbHzzMEBM\D1yLkCwNlUyOs7:TR?= M3PCRVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF4MUSwNFExLz5zNkG0NFAyODxxYU6=
CHO NGHPSI5HfW6ldHnvckBie3OjeR?= NXTLTZdZTGm|cHzhZ4Vu\W62IH;mJJNx\WOrZnnjJGNRNTV3OUSwJIJqdmSrbnegbY4hS0iRIHPlcIx{KHO2YXLsfUB1emGwc3\lZ5Rm\CC5aYToJIh2dWGwIHPhco5i[mmwb3nkJJJm[2WydH;yJFEtKEurPUCuNFI2|ryP Ml\vQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTZzNECwNVAoRjF4MUSwNFExRC:jPh?=
CHO MVvGeY5kfGmxbjDhd5NigQ>? NILTOHZFcXOybHHj[Y1mdnRib3[gd5Bm[2moaXOgR3AuPTV7NECgZolv\GmwZzDpckBEUE9iY3XscJMhe3SjYnz5JJRz[W6|ZnXjeIVlKHerdHigbJVu[W5iY3HucoFjcW6xaXSgdoVk\XC2b4KgNkwhU2l;MT61PO69VQ>? MnnRQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTZzNECwNVAoRjF4MUSwNFExRC:jPh?=
CHOK1 NUO5NpZ3TnWwY4Tpc44h[XO|YYm= MljsSpVv[3Srb37hcEBi[3Srdnn0fUBifCCqdX3hckBESjFicnXj[ZB1d3JidILhcpNn\WO2ZXSgbY4hS0iRS{GgZ4VtdHNiYomgX|M2W0eWUG3nZY1u[VNiYYPzZZktKEurPUCuNFAy|ryP NVLKc4pWRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMU[yOlMzQDNpPkG2NlY{Ojh|PD;hQi=>
HEK293 NGDUd3NHfW6ldHnvckBie3OjeR?= MV\EbZNxdGGlZX3lcpQhd2ZiW{PIYXNTNTF2MUexOkBnem:vIHj1cYFvKEOEMTDy[YNmeHSxcjD0doFve2[nY4Tl[EBqdiCKRVuyPVMh[2WubIOsJGtqRTBwMECyNe69VQ>? M3L3eVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF4Mk[zNlg{Lz5zNkK2N|I5OzxxYU6=
CHO M1;LZ2Z2dmO2aX;uJIF{e2G7 NIf2UFhFcXOybHHj[Y1mdnRib3[gX|NJZVOUMUSxO|E3SSCocn;tJIh2dWGwIFPCNUBz\WOncITvdkBmgHC{ZYPz[YQhcW5iQ1jPJINmdGy|LDDLbV0xNjByNUVOwG0> NX;OWG1qRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMU[yO|k5ODlpPkG2Nlc6QDB7PD;hQi=>
HEK293 NIP6R2xHfW6ldHnvckBie3OjeR?= M4T2PGRqe3CuYXPlcYVvfCCxZjDbN2heW1JvMUSxO|E3KG[{b32gbJVu[W5iQ1KxJJJm[2WydH;yJIV5eHKnc4Pl[EBqdiCKRVuyPVMh[2WubIOsJGtlRTBwMECxPO69VQ>? NFfRXmo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zN{CwOFcyOid-MUewNFQ4OTJ:L3G+
HEK293 NYrxe|B6TnWwY4Tpc44h[XO|YYm= MYfEbZNxdGGlZX3lcpQhd2ZiW{PIYWNRNTV3OUSwJIZzd21iaIXtZY4hS0JzIILlZ4VxfG:{IHX4dJJme3OnZDDpckBJTUt{OUOgZ4VtdHNuIFvpQVAvODB5Md88US=> MXq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yPzByNEexNkc,OTdyMES3NVI9N2F-
HEK293 MkixSpVv[3Srb36gZZN{[Xl? MlS4SIl{eGyjY3Xt[Y51KG:oIGuzTH1YUU5vNUWyNVIuOiCocn;tJIh2dWGwIFPCNUBz\WOncITvdkBmgHC{ZYPz[YQhcW5iSFXLNlk{KGOnbHzzMEBMcT1yLkCxPO69VQ>? NIP1foY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zN{CwOFcyOid-MUewNFQ4OTJ:L3G+
CHO MUnGeY5kfGmxbjDhd5NigQ>? NYDYOphLUW6qaXLpeIlwdiCxZjDbN2heS1BvNUW5OFAh[mmwZHnu[{B1dyCqdX3hckBz\WOxbXLpcoFvfCCFQkGgdoVk\XC2b4KgbY4hS0iRIHPlcIx{NCCLQ{WwQVAvODB4Md88US=> NVrPRnBKRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUexPFEyOzhpPkG3NVgyOTN6PD;hQi=>
CHO MXzGeY5kfGmxbjDhd5NigQ>? NXjE[2ZHUW6qaXLpeIlwdiCxZjDbN2heS1BvNUW5OFAh[mmwZHnu[{B1dyCqdX3hckBz\WOxbXLpcoFvfCCFQkKgdoVk\XC2b4KgbY4hS0iRIHPlcIx{NCCLQ{WwQVAvPs7:TR?= MkDGQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTdzOEGxN|goRjF5MUixNVM5RC:jPh?=
CHO NGfyfo1HfW6ldHnvckBie3OjeR?= MlXFSIl{eGyjY3Xt[Y51KG:oIGuzTH1EWC13NUm0NEBnem:vIHj1cYFvKHKnY3;tZolv[W62IFPCNUBz\WOncITvdkBmgHC{ZYPz[YQhcW5iQ1jPJINmdGy|LDDJR|UxRTBwMEC2Ne69VQ>? MUC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yPzJ7M{GwPUc,OTd{OUOxNFk9N2F-
CHO MVzGeY5kfGmxbjDhd5NigQ>? Ml24SIl{eGyjY3Xt[Y51KG:oIGuzTH1EWC13NUm0NEBnem:vIHj1cYFvKHKnY3;tZolv[W62IFPCNkBz\WOncITvdkBmgHC{ZYPz[YQhcW5iQ1jPJINmdGy|LDDJR|UxRTBwNkCzN:69VQ>? M4Xxc|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF5MkmzNVA6Lz5zN{K5N|ExQTxxYU6=
HEK293 NUPXR|hFTnWwY4Tpc44h[XO|YYm= M{fXemRqe3CuYXPlcYVvfCCxZjDbN2heS1BvNUW5OFQxKG[{b32gbJVu[W5iQ1KxJJJm[2WydH;yJIV5eHKnc4Pl[EBqdiCKRVuyPVMh[2WubIOsJGtqRTBwMECxNe69VQ>? M{LtXFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF5M{izNVgxLz5zN{O4N|E5ODxxYU6=
HEK293 NHi3NpZHfW6ldHnvckBie3OjeR?= NG\MPYFFcXOybHHj[Y1mdnRib3[gX|NJZUOSLUW1PVQxKG[{b32gbJVu[W5icnXjc41jcW6jboSgR2IyKHKnY3XweI9zKGW6cILld5Nm\CCrbjDISWszQTNiY3XscJMtKEurPUCuNFE3|ryP NFXyeWg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zN{m0NlMxPyd-MUe5OFI{ODd:L3G+
HEK293 MWfGeY5kfGmxbjDhd5NigQ>? MX;EbZNxdGGlZX3lcpQhd2ZiW{PIYWNRNTV3OUSwJIZzd21iaIXtZY4hemWlb33ibY5idnRiQ1KyJJJm[2WydH;yJIV5eHKnc4Pl[EBqdiCKRVuyPVMh[2WubIOsJGtqRTFwNkVOwG0> MoXGQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTd7NEKzNFcoRjF5OUSyN|A4RC:jPh?=
HEK293 NUPFSIlWTnWwY4Tpc44h[XO|YYm= Ml\OSIl{eGyjY3Xt[Y51KG:oIGuzTH1EWC13NUm0NEBnem:vIHj1cYFvKHKnY3;tZolv[W62IFPCNUBz\WOncITvdkBmgHC{ZYPz[YQhcW5iSFXLNlk{KGOnbHzzMEBMcT1yLkC0O:69VQ>? NYC5TJpURGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUe5O|kzPjFpPkG3PVc6OjZzPD;hQi=>
CHOK1 MUfGeY5kfGmxbjDhd5NigQ>? MYnEbZNxdGGlZX3lcpQhd2ZiW{PIYXdKVi13NUKxNlIh\nKxbTDoeY1idiC{ZXPvcYJqdmGwdDDDRlIhemWlZYD0c5Ih\XiycnXzd4VlKGmwIFPIU2syKGOnbHzzMEBMcT1zLkm5{txO NGS1SGo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zN{m3PVI3OSd-MUe5O|kzPjF:L3G+
HEK293 M2\N[WZ2dmO2aX;uJIF{e2G7 Mo\5SIl{eGyjY3Xt[Y51KG:oIILh[IlwdGmpYX7kJIZzd21iaIXtZY4hS0JzIILlZ4VxfG:{IHX4dJJme3OnZDDpckBJTUt{OUOgZ4VtdHNuIFvpQVAvODBzON88US=> MVq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDB6M{W2NEc,OThyOEO1OlA9N2F-
HEK293 EBNA M2DydmZ2dmO2aX;uJIF{e2G7 MVzJcpZmenOnIHHnc45qe3RiYXP0bZZqfHliYYSgbJVu[W5iQ1KxJJJm[2WydH;yJIV5eHKnc4Pl[EBqdiCKRVuyPVMhTUKQQTDj[YxteyCkeTDbN|VUZUeWUHfhcY1iWyCrbnPvdpBwemG2aX;uJIF{e2G7LDDFR|UxRTBwMEC0{txO MXO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDB6M{W2NEc,OThyOEO1OlA9N2F-
HEK293 MXzGeY5kfGmxbjDhd5NigQ>? NH\kS5VFcXOybHHj[Y1mdnRib3[gdoFlcW:uaXfhcoQh\nKxbTDoeY1idiCFQkKgdoVk\XC2b4Kg[ZhxemW|c3XkJIlvKEiHS{K5N{Bk\WyuczygT4k:OC53NUVOwG0> Mn;QQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOThyOEO1OlAoRjF6MEizOVYxRC:jPh?=
CHOK1 MljuSpVv[3Srb36gZZN{[Xl? Mn;lRY51[WexbnnzeEBi[3Srdnn0fUBifCCqdX3hckBESjFicnXj[ZB1d3JiZYjwdoV{e2WmIHnuJGNJV0tzIHPlcIx{KGK7IHz1Z4ln\XKjc3WgZZN{[XluIFnDOVA:OC5zMt88US=> M3PEUVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6MkSzO|EyLz5zOEK0N|cyOTxxYU6=
CHOK1 M3LIfGZ2dmO2aX;uJIF{e2G7 M{KwXmRqe3CuYXPlcYVvfCCxZjDbN2heX0mQLUW1NlEzNTJiZoLvcUBpfW2jbjDDRlIhemWlZYD0c5Ih\XiycnXzd4VlKGmwIFPIU2syKGOnbHzzMEBKSzVyPUGuO|bPxE1? MVu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDJ2M{exNUc,OTh{NEO3NVE9N2F-
HEK M4DuS2Z2dmO2aX;uJIF{e2G7 NFjBW3dFcXOybHHj[Y1mdnRib3[gX|NJZUOSLUW1PVQxKG[{b32gbJVu[W5icnXjc41jcW6jboSgR2IyKHKnY3XweI9zKGW6cILld5Nm\CCrbjDISWsh[2WubIOsJGtqRTBwMEGy{txO MXe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDJ7M{mwPEc,OTh{OUO5NFg9N2F-
HEK M1\hRWZ2dmO2aX;uJIF{e2G7 NGT3NZpFcXOybHHj[Y1mdnRib3[gX|NJZUOSLUW1PVQxKG[{b32gbJVu[W5icnXjc41jcW6jboSgR2IzKHKnY3XweI9zKGW6cILld5Nm\CCrbjDISWsh[2WubIOsJGtqRTBwN{pOwG0> MnP6QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTh{OUO5NFgoRjF6MkmzPVA5RC:jPh?=
HEK293 NEjYdIpHfW6ldHnvckBie3OjeR?= NVPWU3FUTGm|cHzhZ4Vu\W62IH;mJHs{UF2FUD21OVk1OCCocn;tJIh2dWGwIFPCNXIh\XiycnXzd4VlKGmwIFjFT|I6OyClZXzsd{whU2l;MD6wNFbPxE1? NInKOmM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOEOzOVk4Pid-MUizN|U6PzZ:L3G+
CHO M1XJbWZ2dmO2aX;uJIF{e2G7 MVrEbZNxdGGlZX3lcpQhd2ZiW{PIYXdKVi13NUKxNk0zKG[{b32gbJVu[W5iY3HucoFjcW6xaXSgR2IzKHKnY3XweI9zKGW6cILld5Nm\CCrbjDDTG8h[2WubIOsJGlEPTB;MT63Ou69VQ>? MnO1QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTh|M{ewPVYoRjF6M{O3NFk3RC:jPh?=
CHO NWXpdXY3TnWwY4Tpc44h[XO|YYm= MnTNSIl{eGyjY3Xt[Y51KG:oIGuzTH1EWC13NUm0NEBnem:vIHj1cYFvKEOEMTDy[YNmeHSxcjDlfJBz\XO|ZXSgbY4hS0iRIHPlcIx{NCCNaU2wMlAzPc7:TR?= NI\a[HQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOEO0NlQxOyd-MUizOFI1ODN:L3G+
CHO NH;meWhHfW6ldHnvckBie3OjeR?= MUnEbZNxdGGlZX3lcpQhd2ZiW{PIYXdKVi13NUKxNk0zKG[{b32gbJVu[W5iQ1KyJJJm[2WydH;yJIV5eHKnc4Pl[EBqdiCFSF:gZ4VtdHNuIFvpQVEvPTkQvF2= M{TsS|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6M{SyOFA{Lz5zOEO0NlQxOzxxYU6=
HEK293 MnfNSpVv[3Srb36gZZN{[Xl? MXfEbZNxdGGlZX3lcpQhd2ZiW{PIYWNRNTV3OUSwJIZzd21iaIXtZY4hS0JzIILlZ4VxfG:{IHX4dJJme3OnZDDpckBJTUt{OUOgZ4VtdHNuIFvpQVAvODB{NN88US=> M2TLWVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6M{[zN|UzLz5zOEO2N|M2OjxxYU6=
CHO M2i4eWZ2dmO2aX;uJIF{e2G7 NED4T2pFcXOybHHj[Y1mdnRib3[gX|NJZUOSLUW1PVQxKG[{b32gbJVu[W5iQ1KyJJJm[2WydH;yJIV5eHKnc4Pl[EBqdiCFSF:gZ4VtdHNuIFvpQVAvPTcQvF2= NHG2VYY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOEO2N|M2Oid-MUizOlM{PTJ:L3G+
SF9 M3i0fWZ2dmO2aX;uJIF{e2G7 Mnu0RY51[WexbnnzeEBi[3Srdnn0fUBifCC{YYSgR2IyKHKnY3XweI9zKGmwIGPGPUBk\WyuczDhd5Nme3OnZDDhd{BqdmirYnn0bY9vKG:oIFPQMVU2QTRyLYP0bY12dGG2ZXSgS3RR\2GvbXHTJIJqdmSrbnesJGtqRTBwMECwN|HPxE1? M2mxU|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6NES4N|QxLz5zOES0PFM1ODxxYU6=
SF9 MmjtSpVv[3Srb36gZZN{[Xl? M3;nN2FvfGGpb37pd5Qh[WO2aY\peJkh[XRiaIXtZY4hS0JzIILlZ4VxfG:{IHX4dJJme3OnZDDpckBUTjliY3XscJMh[XO|ZYPz[YQh[XNiaX7obYJqfGmxbjDv[kBEWC13NUm0NE1{fGmvdXzheIVlKEeWUHfhcY1iWyCkaX7kbY5oNCCNaU2wMlAxODR|zszN MoXXQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTh2NEizOFAoRjF6NES4N|QxRC:jPh?=
SF9 MmTJSpVv[3Srb36gZZN{[Xl? M4C3W2lvfmW{c3WgZYdwdmm|dDDheEBpfW2jbjDDRlEhemWlZYD0c5Ih\XiycnXzd4VlKGmwIGPGPUBk\WyuczDhd5Nme3OnZDDhd{Bl\WO{ZXHz[UBqdiCJVGDnZY1u[VNibHX2[YwtKEmFNUC9NE4xODF|Nd88US=> NVLrOm9oRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUi0OFg{PDBpPkG4OFQ5OzRyPD;hQi=>
SF9 M3zlWWZ2dmO2aX;uJIF{e2G7 MUDBcpRi\2:waYP0JIFkfGm4aYT5JIF1KGi3bXHuJGNDOiC{ZXPldJRweiCrbjDTSlkh[2WubIOgZZN{\XO|ZXSgZZMhcW6qaXLpeIlwdiCxZjDDVE02PTl2MD3zeIlufWyjdHXkJGdVWGejbX3hV{BjcW6maX7nMEBMcT1yLkixOe69VQ>? Ml\mQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTh2NEizOFAoRjF6NES4N|QxRC:jPh?=
HEK293 NYLkRo5LTnWwY4Tpc44h[XO|YYm= MoqySIl{eGyjY3Xt[Y51KG:oIGuzTH1EWC13NUm0NEBnd3KvIHj1cYFvKHKnY3;tZolv[W62IFPCNUBz\WOncITvdkBmgHC{ZYPz[YQhcW5iSFXLNlk{KGOnbHzzJIJ6KGyrcYXp[EB{[2mwdHnscIF1cW:wIHPveY51cW6pLDDLbV0xNjB2zszN M2H0VlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6NUGxNVU4Lz5zOEWxNVE2PzxxYU6=
CHO-K1 M1XrR2Z2dmO2aX;uJIF{e2G7 Mn3aSIl{eGyjY3Xt[Y51KG:oIGuzTH1UWjF2MUexOkBnem:vIHj1cYFvKEOEMTDy[YNmeHSxcjDlfJBz\XO|ZXSgbY4hS0iRLVuxJINmdGy|LDDLbV0xNjByMUG4{txO MofoQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTh3MUK5NFEoRjF6NUGyPVAyRC:jPh?=
HEK293 NHXrVFZHfW6ldHnvckBie3OjeR?= MUPBcpRi\2:waYP0JIFkfGm4aYT5JIF1KGi3bXHuJGNDOSC{ZXPldJRweiCneIDy[ZN{\WRiaX6gTGVMOjl|IHPlcIx{KGG|c3Xzd4VlKGG|IHnubIljcXSrb36gc4YhS1BvNUW5OFAue3SrbYXsZZRm\CCdM{XTYWdVWGejbX3hV{BjcW6maX7nMEBM\D1yLkCwNlU4|ryP M3j0SVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6NUGyPVAyLz5zOEWxNlkxOTxxYU6=
HEK293 MmLNSpVv[3Srb36gZZN{[Xl? NHrUO5NFcXOybHHj[Y1mdnRib3[gX|NJZUOSLUW1PVQxKG[{b32gbJVu[W5iQ1KxJJJm[2WydH;yJIV5eHKnc4Pl[EBqdiCKRVuyPVMh[2WubIOsJGtqRTBwMEC2NVjPxE1? MlTTQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTh3MUK5NFEoRjF6NUGyPVAyRC:jPh?=
CHO-K1 M4rvSmZ2dmO2aX;uJIF{e2G7 M{m1T2Rqe3CuYXPlcYVvfCCxZjDbN2heS1BvNUW5OFAh\nKxbTDoeY1idiCFQkKgdoVk\XC2b4Kg[ZhxemW|c3XkJIlvKEOKTz3LNUBk\WyuczygT4k:OC5|MUROwG0> NGjGVJc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOEWxNlkxOSd-MUi1NVI6ODF:L3G+
HEK NIf0fIdHfW6ldHnvckBie3OjeR?= NYrsV3o{TGm|cHzhZ4Vu\W62IH;mJHs{UF2FUD21OVk1OCCocn;tJIh2dWGwIILlZ49u[mmwYX70JGNDOSC{ZXPldJRweiCneIDy[ZN{\WRiaX6gTGVMKGOnbHzzMEBMcT1yLkCwPO69VQ>? NVfOR2tDRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUi1O|k{QDZpPkG4OVc6Ozh4PD;hQi=>
HEK NUTuU4pJTnWwY4Tpc44h[XO|YYm= MlTNSIl{eGyjY3Xt[Y51KG:oIGuzTH1EWC13NUm0NEBnem:vIHj1cYFvKHKnY3;tZolv[W62IFPCNkBz\WOncITvdkBmgHC{ZYPz[YQhcW5iSFXLJINmdGy|LDDLbV0xNjd7zszN Ml\YQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTh3N{mzPFYoRjF6NUe5N|g3RC:jPh?=
HEK293 Mn3PSpVv[3Srb36gZZN{[Xl? NHWzSXNFcXOybHHj[Y1mdnRib3[gX|NJZUOSLUW1PVQxKG[{b32gbJVu[W5iQ1KxJJJm[2WydH;yJIV5eHKnc4Pl[EBqdiCKRVuyPVMh[2WubIOsJGtqRTBwMEGy{txO MXy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDZ6MEK3Okc,OTh4OECyO|Y9N2F-
HEK293 NYGyOWJRTnWwY4Tpc44h[XO|YYm= MXnEbZNxdGGlZX3lcpQhd2ZiW{PIYWNRNTV3OUSwJIZzd21iaIXtZY4hS0J{IILlZ4VxfG:{IHX4dJJme3OnZDDpckBJTUt{OUOgZ4VtdHNuIFvpQVAvPzoQvF2= M3\MO|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6NkiwNlc3Lz5zOE[4NFI4PjxxYU6=
HEK293 NYHGR|hzTnWwY4Tpc44h[XO|YYm= NH7QNY9FcXOybHHj[Y1mdnRib3[gX|NJZUOSLUW1PVQxKG[{b32gbJVu[W5iQ1KxJJJm[2WydH;yJIV5eHKnc4Pl[EBqdiCKRVuyPVMh[2WubIOsJGlEPTB;MD6wNVXPxE1? Moj6QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTh5MUK4OVYoRjF6N{GyPFU3RC:jPh?=
HEK293 MVnGeY5kfGmxbjDhd5NigQ>? M{S0c2FvfGGpb37pd5Qh[WO2aY\peJkh[XRiaIXtZY4hS0JzIILlZ4VxfG:{IHX4dJJme3OnZDDpckBJTUt{OUOgZ4VtdHNiYYPz[ZN{\WRiYYOgbY5pcWKrdHnvckBw\iCHdT3HWHAh[mmwZHnu[{whTUN3ME2wMlAyQDMQvF2= MXO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDdzMki1Okc,OTh5MUK4OVY9N2F-
HEK293 M{DWUGZ2dmO2aX;uJIF{e2G7 NEXhT3dFcXOybHHj[Y1mdnRib3[gX|NJZUOSLUW1PVQxKG[{b32gbJVu[W5iQ1KyJJJm[2WydH;yJIV5eHKnc4Pl[EBqdiCKRVuyPVMh[2WubIOsJGlEPTB;MT65N|k5|ryP MmrEQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTh5MUK4OVYoRjF6N{GyPFU3RC:jPh?=
HEK293 NELMbJVHfW6ldHnvckBie3OjeR?= NWq3[nd[UW64ZYLz[UBi\2:waYP0JIFkfGm4aYT5JIF1KGi3bXHuJGNDOSC{ZXPldJRweiCneIDy[ZN{\WRiaX6gTGVMOjl|IHPlcIx{KGG|c3Xzd4VlKGG|IHTlZ5Jm[XOnIHnuJHs{PVOfZ3HtcYFIXFBiYnnu[Ilv\yC{ZXzheIl3\SC2bzDjc451em:u MVS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDdzMki1Okc,OTh5MUK4OVY9N2F-
CHO Mlj3SpVv[3Srb36gZZN{[Xl? NF3KZmpCdnSjZ3;ubZN1KGGldHn2bZR6KGG2IHj1cYFvKEOEMTDy[YNmeHSxcjDpckBEUE9iY3XscJMh[XO|ZYPz[YQh[XNiR2TQ[4FudWGVIHLpcoRqdmduIFviQVAvODByNkm4{txO M2HwfFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6OECwO|cxLz5zOEiwNFc4ODxxYU6=
CHOK1 NEXSeI1HfW6ldHnvckBie3OjeR?= MnzCSIl{eGyjY3Xt[Y51KG:oIGuzTH1YUU5vNUWyNVIuOiCocn;tJIh2dWGwIFPCNkBz\WOncITvdkBmgHC{ZYPz[YQhcW5iQ1jPT|Eh[2WubIOgZpkhdGmzdXnkJJNkcW62aXzsZZRqd25ic4DlZ5Rzd22ndIL5MEBKSzVyPUGuO|bPxE1? MX28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDl3NEC0Nkc,OTh7NUSwOFI9N2F-
CHO M3eyUGZ2dmO2aX;uJIF{e2G7 NX7qfVQyTGm|cHzhZ4Vu\W62IH;mJHs{UF2ZSV6tOVUzOTJvMjDmdo9uKGi3bXHuJGNDOiC{ZXPldJRweiCneIDy[ZN{\WRiaX6gR2hQKGOnbHzzMEBKSzVyPUGuO|bPxE1? M4\PblxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF7MEKyOlY3Lz5zOUCyNlY3PjxxYU6=
HEK293 NVThfFI6TnWwY4Tpc44h[XO|YYm= M1X1[WRqe3CuYXPlcYVvfCCxZjDbN2heS1BvNUW5OFAh\nKxbTDoeY1idiCFQkKgdoVk\XC2b4Kg[ZhxemW|c3XkJIlvKEiHS{K5N{Bk\WyuczygTWM2OD1yLkCwNVnPxE1? M3fpNlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF7MEm1OFQ1Lz5zOUC5OVQ1PDxxYU6=
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HEK293 Mm[4SpVv[3Srb36gZZN{[Xl? MX\BcpRi\2:waYP0JIFkfGm4aYT5JIF1KGi3bXHuJGNDOSC{ZXPldJRweiCneIDy[ZN{\WRiaX6gTGVMOjl|IHPlcIx{KGG|c3Xzd4VlKGG|IHnubIljcXSrb36gc4YhTXVvR2TQJIJqdmSrbnesJGVEPTB;MD6wNVgz|ryP MXq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQTB7NUS0OEc,OTlyOUW0OFQ9N2F-
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CHOK1 M1zldGZ2dmO2aX;uJIF{e2G7 NWe0W4Y6SW62YXfvcol{fCCjY4Tpeol1gSCjdDDoeY1idiClYX7uZYJqdm:rZDDDRlEhemWlZYD0c5Ih\XiycnXzd4VlKGmwIFPIU2syKGOnbHzzJIF{e2W|c3XkJIF{KGODTWCgZYN1cX[rdImsJGVEPTB;MD6yOO69VQ>? MX28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQTN{OE[4N{c,OTl|Mki2PFM9N2F-
CHOK1 M2P6UGZ2dmO2aX;uJIF{e2G7 NFO5XoxCdnSjZ3;ubZN1KGGldHn2bZR6KGG2IHj1cYFvKGOjbn7hZolvd2mmIFPCNkBz\WOncITvdkBmgHC{ZYPz[YQhcW5iQ1jPT|Eh[2WubIOgZZN{\XO|ZXSgZZMh[0GPUDDhZ5Rqfmm2eTygSWM2OD1|MT6yNe69VQ>? M{j5[lxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF7M{K4Olg{Lz5zOUOyPFY5OzxxYU6=
HEK293 NUjob5lRTnWwY4Tpc44h[XO|YYm= NFO2fVhFcXOybHHj[Y1mdnRib3[gX|NJZVOUMUSxO|E3KG[{b32gbJVu[W5icnXjc41jcW6jboSgR2IyKHKnY3XweI9zKGW6cILld5Nm\CCrbjDISWszQTNiY3XscJMtKEurPUCuNFAyQTl3zszN M4TxZ|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF7M{O4N|U3Lz5zOUOzPFM2PjxxYU6=
HEK293 M2G5WmZ2dmO2aX;uJIF{e2G7 M1S0V2Rqe3CuYXPlcYVvfCCxZjDbN2heW1JzNEG3NVYh\nKxbTDoeY1idiC{ZXPvcYJqdmGwdDDDRlIhemWlZYD0c5Ih\XiycnXzd4VlKGmwIFjFT|I6OyClZXzsd{whU2l;MD6zPVgyOc7:TR?= NEfkeIU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOUOzPFM2Pid-MUmzN|g{PTZ:L3G+
CHOK1 NXLwVVlvTnWwY4Tpc44h[XO|YYm= NX3pe3dVOTBibXnudy=> NXfRV|I3SW62YXfvcol{fCCjY4Tpeol1gSCjdDDoeY1idiCFQkGgdoVk\XC2b4Kg[ZhxemW|c3XkJIlvKEOKT1uxJINmdGy|IHHzd4V{e2WmIHHzJIlvcGmkaYTpc44hd2ZiQ2CtOVU6PDBvaX7keYNm\CC{ZYPwc45{\SCjZoTldkAyOCCvaX7zJIJ6KEeWUHfhcY1iYzN3U22gZolv\GmwZzDhd5NigSxiS3m9NE4xODF4zszN NYr5eVN[RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUmzOVEyOTNpPkG5N|UyOTF|PD;hQi=>
HEK293 NE\ucYNHfW6ldHnvckBie3OjeR?= NUXY[|RoTGm|cHzhZ4Vu\W62IH;mJHs{UF2{aX3vcoFj[W62IH\yc40hcHWvYX6gR2IyKHKnY3XweI9zKGW6cILld5Nm\CCrbjDISWszQTNiY3XscJMh[nlibHnxeYllKHOlaX70bYxt[XSrb36gZ492dnSrbnesJGtqRTBwMECxPe69VQ>? NHP2dpo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOUWyNFU4Oid-MUm1NlA2PzJ:L3G+
HEK293 Mne4SpVv[3Srb36gZZN{[Xl? NF7USpJFcXOybHHj[Y1mdnRib3[gX|NJZUOSLUW1PVQxKG[{b32gbJVu[W5icnXjc41jcW6jboSgR2IyWiCneIDy[ZN{\WRiaX6gTGVMOjl|IHPlcIx{NCCLQ{WwQVAvODF|Mt88US=> M1PPZlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF7NUOwOlk4Lz5zOUWzNFY6PzxxYU6=
HEK293 MXzGeY5kfGmxbjDhd5NigQ>? NHjLcWVKdn[ncoPlJIFod26rc4SgZYN1cX[rdImgZZQhcHWvYX6gdoVkd22kaX7hcpQhS0JzUjDlfJBz\XO|ZXSgbY4hUEWNMkmzJINmdGy|IHHzd4V{e2WmIHHzJIlvcGmkaYTpc44hd2ZiQ2CtOVU6PDBvc4TpcZVt[XSnZDDFeU1IXFBiYnnu[Ilv\yxiRVO1NF0xNjBzNUhOwG0> M160eFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF7NUOwOlk4Lz5zOUWzNFY6PzxxYU6=
HEK293 MV7GeY5kfGmxbjDhd5NigQ>? NIXsUZVFcXOybHHj[Y1mdnRib3[gX|NJZUOSLUW1PVQxKG[{b32gbJVu[W5icnXjc41jcW6jboSgR2IzWiCneIDy[ZN{\WRiaX6gTGVMOjl|IHPlcIx{NCCLQ{WwQVEvPjNzMd88US=> NIXJ[VU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOUWzNFY6Pyd-MUm1N|A3QTd:L3G+
HEK293 M1:wcmZ2dmO2aX;uJIF{e2G7 NEDGS4UyOCC3TR?= NVPufGVuUW62cnnud4lkKGGldHn2bZR6KGG2IHj1cYFvKHKnY3;tZolv[W62IFPCNXIh\XiycnXzd4VlKGmwIFjFT|I6OyClZXzsd{Bie3Onc4Pl[EBieyCHdT3HWHAh[mmwZHnu[{BifCBzMDD1UUBz\WyjdHn2[UB1dyCkYYPhcEBt\X[nbB?= MY[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQTV|ME[5O{c,OTl3M{C2PVc9N2F-
HEK M3vZXmZ2dmO2aX;uJIF{e2G7 MXHEbZNxdGGlZX3lcpQhd2ZiW{PIYWNRNTV3OUSwJIZzd21iaIXtZY4hemWlb33ibY5idnRiQ1KxJJJm[2WydH;yJIV5eHKnc4Pl[EBqdiCKRVugZ4VtdHNuIFvpQVAvODF{zszN M1PqbFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF7NUm1OVk3Lz5zOUW5OVU6PjxxYU6=
HEK NWroWooxTnWwY4Tpc44h[XO|YYm= NXLEdnFrTGm|cHzhZ4Vu\W62IH;mJHs{UF2FUD21OVk1OCCocn;tJIh2dWGwIILlZ49u[mmwYX70JGNDOiC{ZXPldJRweiCneIDy[ZN{\WRiaX6gTGVMKGOnbHzzMEBMcT1yLke5{txO M1vBWlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF7NUm1OVk3Lz5zOUW5OVU6PjxxYU6=
CHO-K1 MXTGeY5kfGmxbjDhd5NigQ>? NVvTWXFJSW62YXfvcol{fCCjY4Tpeol1gSCjdDDoeY1idiCFQkGgdoVk\XC2b4KgeJJidnOoZXP0[YQhcW5iQ1jPMWsy[2WubIOgZpkhT1SSZ3HtcYFcOzWVXTDibY5lcW6pIHHzd4F6NCCNaU2wMlAxOTcQvF2= NW\QcpBWRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUm2PFM6OThpPkG5Olg{QTF6PD;hQi=>
CHO MoXESpVv[3Srb36gZZN{[Xl? NE\G[Y1DcW6maX7nJIFn\mmwaYT5JJRwKGi3bXHuJGNDOiC{ZXPldJRweiCneIDy[ZN{\WRiaX6gR2hQKGOnbHzzJIJ6KGy3Y3nm[ZJie2VicnXwc5J1\XJiZ3Xu[UBie3OjeTygTWM2OD1yLkC5NlXPxE1? M{n3ZlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF7OEWwOFc{Lz5zOUi1NFQ4OzxxYU6=
CHOK1 MXrGeY5kfGmxbjDhd5NigQ>? NX3xXJRpTGm|cHzhZ4Vu\W62IH;mJHs{UF2ZSV6tOVUzOTJ{IH\yc40hcHWvYX6gR2IzKHKnY3XweI9zKGW6cILld5Nm\CCrbjDDTG9MOSClZXzsd{whUUN3ME2xMlc3|ryP NIi3VlA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOUi1NFQ4Oyd-MUm4OVA1PzN:L3G+
CHO-K1 NFvNdJFHfW6ldHnvckBie3OjeR?= NU\TeWhJSW62YXfvcol{fCCjY4Tpeol1gSCjdDDoeY1idiC{ZXPvcYJqdmGwdDDDRlEhemWlZYD0c5Ih\XiycnXzd4VlKGmwIFPIU{1MOSClZXzsd{Bie3Onc4Pl[EBieyCrbnjpZol1cW:wIH;mJGNRNTV3OUSwMZN1cW23bHH0[YQhT1SSZ3HtcYFUKGKrbnTpcoctKEmFNUC9NE4xODR3zszN NF\Ke5M9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOUm1OFk4QCd-MUm5OVQ6Pzh:L3G+
CHO-K1 MWrGeY5kfGmxbjDhd5NigQ>? M4DIVmlvfmW{c3WgZYdwdmm|dDDhZ5Rqfmm2eTDheEBpfW2jbjDDRlEhemWlZYD0c5Ih\XiycnXzd4VlKGmwIFPIU{1MOSClZXzsd{BjgSCJVGDnZY1u[VNiYnnu[Ilv\yCjc4PhfUwhUUN3ME2wMlAxOjoQvF2= MomwQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjByMUW2OFcoRjJyMEG1OlQ4RC:jPh?=
CHO-K1 NW\lUJBETnWwY4Tpc44h[XO|YYm= NEe1T49CdnSjZ3;ubZN1KGGldHn2bZR6KGG2IHj1cYFvKEOEMTDy[YNmeHSxcjDlfJBz\XO|ZXSgbY4hS0iRLVuxJINmdGy|IHHzd4V{e2WmIHHzJIlvcGmkaYTpc44hd2ZiQ2CtOVU6PDBvaX7keYNm\CCJVGDnZY1u[VNiYnnu[Ilv\yxiSVO1NF0xNjByNEZOwG0> NYryPI9XRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkCwNVU3PDdpPkKwNFE2PjR5PD;hQi=>
COS7 NH7BO5FHfW6ldHnvckBie3OjeR?= NIDWZ2xFcXOybHHj[Y1mdnRib3[gX|NJZUOSLUW1PVQxKG[{b32gbJVu[W5iQ1KxJJJm[2WydH;yJIV5eHKnc4Pl[EBqdiCFT2O3JINmdGy|LDDJR|UxRTBwMEC1Ne69VQ>? Mn7xQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjByMUW2OFcoRjJyMEG1OlQ4RC:jPh?=
CHO M37L[mZ2dmO2aX;uJIF{e2G7 NYXWW3E2UW64ZYLz[UBi\2:waYP0JIFkfGm4aYT5JIF1KGi3bXHuJJJm[2:vYnnuZY51KEOEMTDy[YNmeHSxcjDlfJBz\XO|ZXSgbY4hS0iRIHPlcIx{KGK7IHz1Z4ln\XKjc3WgdoVxd3K2ZYKg[4Vv\SCjc4PhfUwhUUN3ME2wMlExQM7:TR?= MXq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zODB2NUOzO{c,OjByNEWzN|c9N2F-
CHO MmDGSpVv[3Srb36gZZN{[Xl? MXq2NEBucW6| NYntOYs6UW64ZYLz[UBi\2:waYP0JIFkfGm4aYT5JIF1KGi3bXHuJINidm6jYnnuc4llKEOEMTDy[YNmeHSxcjDlfJBz\XO|ZXSgbY4hS0iRIHPlcIx{KGG|c3Xzd4VlKGG|IHnubIljcXSrb36gc4Yh\m:{c3vvcIlvNXO2aX31cIF1\WRiY1HNVEBi[2O3bYXsZZRqd25iYX\0[ZIhPjBibXnud{whTUN3ME2wMlAxODFzzszN NHzsPZc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MEC0O|c4QSd-MkCwOFc4Pzl:L3G+
CHO M1jW[WZ2dmO2aX;uJIF{e2G7 M2DxeVMhcHK| NXLl[Ix1TGm|cHzhZ4Vu\W62IH;mJHs{UF2FUD21OVk1OCCocn;tJIh2dWGwIILlZ49u[mmwYX70JINidm6jYnnuc4llKEOEMTDy[YNmeHSxcjDlfJBz\XO|ZXSgbY4hS0iRIHPlcIx{KGGodHXyJFMhcHK|IHL5JIxqeXWrZDDzZ4lvfGmubHH0bY9vKGOxdX70bY5oNCCNaU2wMlAxODd2zszN M37MUlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJyMES3O|c6Lz5{MEC0O|c4QTxxYU6=
CHO NGDGem1HfW6ldHnvckBie3OjeR?= MX:xNEBucW6| NX7EUppWSW62YXfvcol{fCCjY4Tpeol1gSCjdDDoeY1idiClYX7uZYJqdm:rZDDDRlEhemWlZYD0c5Ih\XiycnXzd4VlKGmwIFPIU{Bk\WyuczDjc4V5eHKnc4PpcochT2GucHjhNVUwOTZiYYPz[ZN{\WRiYYOgbY5pcWKrdHnvckBw\iCFUD21OVk1OC2rbnT1Z4VlKEOjMjugdoVt\WG|ZTDh[pRmeiBzMDDtbY5{KGK7IH3pZ5JwKHCuYYTlJJJm[WSncjygTWM2OD1yLkCwN|LPxE1? M4SxZ|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJyMES3O|c6Lz5{MEC0O|c4QTxxYU6=
CHO MXTGeY5kfGmxbjDhd5NigQ>? NH;YNmM{KGi{cx?= NUjUVIlyTGm|cHzhZ4Vu\W62IH;mJHs{UF2FUD21OVk1OCCocn;tJIh2dWGwIILlZ49u[mmwYX70JINidm6jYnnuc4llKEOEMjDy[YNmeHSxcjDlfJBz\XO|ZXSgbY4hS0iRIHPlcIx{KGGodHXyJFMhcHK|IHL5JIxqeXWrZDDzZ4lvfGmubHH0bY9vKGOxdX70bY5oNCCNaU2wMlEzPs7:TR?= NYXPdFZYRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkCwOFc4PzlpPkKwNFQ4Pzd7PD;hQi=>
CHO NWPEUm9GTnWwY4Tpc44h[XO|YYm= MXvBcpRi\2:waYP0JIFkfGm4aYT5JIF1KGi3bXHuJGNDOSC{ZXPldJRweiCneIDy[ZN{\WRiaX6gR2hQKGOnbHzzJIF{e2W|c3XkJIF{KGmwaHnibZRqd25ib3[gR3AuPTV7NECtbY5lfWOnZDDbN2he[XKjY3jp[I9vcWNiYXPp[EBz\WynYYPlMEBM\D1yLkCwNlUyOs7:TR?= NVrnSWZNRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkCzOlMyOzJpPkKwN|Y{OTN{PD;hQi=>
CHO NITvSnZHfW6ldHnvckBie3OjeR?= NHzQXIJFcXOybHHj[Y1mdnRib3[gX|NJZUOSLUW1PVQxKG[{b32gbJVu[W5iQ1KxJJJm[2WydH;yJIV5eHKnc4Pl[EBqdiCFSF:gZ4VtdHNuIFvpQVAvODJ3zszN NGDBd5U9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MEO2N|E{Oid-MkCzOlMyOzJ:L3G+
CHO M3PMXWZ2dmO2aX;uJIF{e2G7 MWDEbZNxdGGlZX3lcpQhd2ZiW{PIYWNRNTV3OUSwJIZzd21iaIXtZY4hS0J{IILlZ4VxfG:{IHX4dJJme3OnZDDpckBEUE9iY3XscJMtKEurPUGuOVjPxE1? Mn7jQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjB|NkOxN|IoRjJyM{[zNVMzRC:jPh?=
CHO-K1 NXXnVZdnTnWwY4Tpc44h[XO|YYm= MofGNUBpeg>? NHvER49FcXOybHHj[Y1mdnRib3[gX|NJZVeLTj21OVIyOi1{IH\yc40hcHWvYX6gR2IzKHKnY3XweI9zKGW6cILld5Nm\CCrbjDDTG8uUzFiY3XscJMh[W[2ZYKgNUBpeiCkeTDsbZF2cWRic3PpcpRqdGyjdHnvckBkd3WwdHnu[{whUUN3ME2xMlc3|ryP NFTJNYI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{ME[3N|czQSd-MkC2O|M4Ojl:L3G+
HEK M3\tXWZ2dmO2aX;uJIF{e2G7 NVfh[|B{TGm|cHzhZ4Vu\W62IH;mJHs{UF2FUD21OVk1OCCocn;tJIh2dWGwIFPCNUBz\WOncITvdkBmgHC{ZYPz[YQhcW5iSFXLJINmdGy|LDDLbV0xNjBzMt88US=> NXL3UmxoRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkC3NVg1QTJpPkKwO|E5PDl{PD;hQi=>
HEK NVvpWpBbTnWwY4Tpc44h[XO|YYm= NIn0R2lFcXOybHHj[Y1mdnRib3[gX|NJZUOSLUW1PVQxKG[{b32gbJVu[W5iQ1KyJJJm[2WydH;yJIV5eHKnc4Pl[EBqdiCKRVugZ4VtdHNuIFvpQVAvPzoQvF2= MljRQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjB5MUi0PVIoRjJyN{G4OFkzRC:jPh?=
CHO NFXG[VZHfW6ldHnvckBie3OjeR?= MYLB[49vcXO2IHHjeIl3cXS7IHH0JIh2dWGwIFPCNUBz\WOncITvdkBmgHC{ZYPz[YQhcW5iQ1jPJINmdGy|IHPvMYV5eHKnc4PpcochT2GucHjhNVYheHKxdHXpckBie3Onc4Pl[EBieyCvb3LpcIl7[XSrb36gc4YhcW62cnHj[YxtfWyjcjDjZYxkcXWvLDDL[V0xNjByMUJOwG0> NH\xfY49[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MEi0OVk2QSd-MkC4OFU6PTl:L3G+
HEK293 NHP4cGhHfW6ldHnvckBie3OjeR?= NVy2NmdTTGm|cHzhZ4Vu\W62IH;mJHs{UF2VUkG0NVcyPiCocn;tJIh2dWGwIFPCNUBz\WOncITvdkBmgHC{ZYPz[YQhcW5iSFXLNlk{KGOnbHzzMEBMcT1yLkCwNVE5|ryP NWnEW4R3RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkC4OFU6PTlpPkKwPFQ2QTV7PD;hQi=>
HEK293 M1jMPGZ2dmO2aX;uJIF{e2G7 NIf0eZJFcXOybHHj[Y1mdnRib3[gX|NJZUOSNUW5OFAh\nKxbTDoeY1idiCFQkGgdoVk\XC2b4Kg[ZhxemW|c3XkJIlvKEiHS{K5N{Bk\WyuczygT4k:OC5yME[xPO69VQ>? MX28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zODh2NUm1PUc,OjB6NEW5OVk9N2F-
CHOK1 M3i0VWZ2dmO2aX;uJIF{e2G7 NH\3bHJFcXOybHHj[Y1mdnRib3[gX|NJZUOSNUW5OFAh\nKxbTDoeY1idiCFQkKgdoVk\XC2b4Kg[ZhxemW|c3XkJIlvKEOKT1uxJINmdGy|LDDLbV0xNjNzM988US=> M{LkdVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJyOES1PVU6Lz5{MEi0OVk2QTxxYU6=
HEK NXLVZ2ZZTnWwY4Tpc44h[XO|YYm= NVGxPWtHTGm|cHzhZ4Vu\W62IH;mJHs{UF2FUD21OUw6PDBiZoLvcUBz\WOxbXLpcoFvfCCqdX3hckBESjFicnXj[ZB1d3JidILhcpNn\WO2ZXSgbY4hUEWNIHPlcIx{NCCNaU2wMlAyOs7:TR?= NXr1clQ6RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkC5OFMzQTBpPkKwPVQ{OjlyPD;hQi=>
HEK NHvUTWlHfW6ldHnvckBie3OjeR?= MljKSIl{eGyjY3Xt[Y51KG:oIGuzTH1EWC13NTy5OFAh\nKxbTDy[YNwdWKrbnHueEBpfW2jbjDDRlIhemWlZYD0c5IhfHKjboPm[YN1\WRiaX6gTGVMKGOnbHzzMEBMcT1yLke5{txO M{DKNFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJyOUSzNlkxLz5{MEm0N|I6ODxxYU6=
CHO MkjuSpVv[3Srb36gZZN{[Xl? NFLrZmFFcXOybHHj[Y1mdnRib3[gX|NJZVOUMUSxO|E3SSCocn;tJIh2dWGwIFPCNUBz\WOncITvdkBmgHC{ZYPz[YQhcW5iQ1jPJINmdGy|LDDLbV0xNjByMEmzN|PPxE1? MX:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTN|NEi5Nkc,OjF|M{S4PVI9N2F-
Sf9 M4nvT2Z2dmO2aX;uJIF{e2G7 NGe1cGxFcXOybHHj[Y1mdnRib3[gX|NJZUOSNUW5OFAh\nKxbTDoeY1idiC{ZXPvcYJqdmGwdDDDRlIhemWlZYD0c5Ih\XiycnXzd4VlKGmwIGPmPUBk\WyuczygT4k:OC56NUGxOO69VQ>? MVy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTN|NEi5Nkc,OjF|M{S4PVI9N2F-
CHO NGDkR|ZHfW6ldHnvckBie3OjeR?= NILkbYdCdnSjZ3;ubZN1KGGldHn2bZR6KGG2IFPCNUBz\WOncITvdkB1emGwc3\lZ5Rm\CCrbjDDTG8h[2WubIOg[ZhxemW|c3nu[{BieG:jZYH1c5JqdiCjczDhJJJmeG:{dHXyJIZweiCJLYDyc5RmcW5vY3;1dIxm\CC{ZXPldJRwei2vZXTpZZRm\CClYXzjbZVuKHOrZ37hcIlv\yCkeTDibY9tfW2rbnXzZ4Vv[2ViYYPzZZktKEmFNUC9NE4xODUQvF2= NWHnXHRURGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkGzO|Y2QDhpPkKxN|c3PTh6PD;hQi=>
HEK293 NFrnc3lHfW6ldHnvckBie3OjeR?= NFn4TYNPd26lb33w[ZRqfGm4ZTDpcohq[mm2aX;uJI9nKE2UUEGtcYVlcWG2ZXSgSVIuOTekZYThS{B1emGwc4DvdpQhcW5iaIXtZY4hVVKSMTDlfJBz\XO|aX7nJGhGUzJ7MzDj[YxteyCkeTDEbZhwdiCybH;0MEBMcT1zLkVOwG0> MYO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTVzMUm0OUc,OjF3MUG5OFU9N2F-
HEK293 NV7ZfW1TTnWwY4Tpc44h[XO|YYm= MmnZUo9v[2:vcHX0bZRqfmViaX7obYJqfGmxbjDv[kBOWlB2LX3l[IlifGWmIFWyMVE4[mW2YVegeJJidnOyb4L0JIlvKGi3bXHuJG1TWDRiZYjwdoV{e2mwZzDISWszQTNiY3XscJMh[nliRHn4c44heGyxdDygT4k:PM7:TR?= M2f0b|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzNUGxPVQ2Lz5{MUWxNVk1PTxxYU6=
HEK293 M32wfWZ2dmO2aX;uJIF{e2G7 NHPIS5dKdmS3Y4Tpc44hd2ZiTWLQNk1u\WSrYYTl[EBGOi1zN3LleIFIKHS{YX7zdI9zfCCrbjDoeY1idiCPUmCyJIV5eHKnc4PpcochUEWNMkmzJINmdGy|IHnuJJBz\XOnbnPlJI9nKDJidV2gSVIuOTekZYThSy=> MV28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTVzMUm0OUc,OjF3MUG5OFU9N2F-
HEK293 NVOxNJpCTnWwY4Tpc44h[XO|YYm= M3;yVGlvcGmkaYTpc44hd2ZiTWLQN{1u\WSrYYTl[EBGOi1zN3LleIFIKHS{YX7zdI9zfCCrbjDoeY1idiCPUmCzJIV5eHKnc4PpcochUEWNMkmzJINmdGy|IHnuJJBz\XOnbnPlJI9nKDF3IIXNJGUzNTF5YnX0ZWc> NED5O3I9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUWxNVk1PSd-MkG1NVE6PDV:L3G+
HEK293 M1r2eGZ2dmO2aX;uJIF{e2G7 M4f6ZWlvcGmkaYTpc44hd2ZiTWLQNU1u\WSrYYTl[EBGOi1zN3LleIFIKHS{YX7zdI9zfCCrbjDoeY1idiCPUmCxJIV5eHKnc4PpcochUEWNMkmzJINmdGy|IHnuJJBz\XOnbnPlJI9nKDBwNjD0c{A2KHWPIFWyMVE4[mW2YVe= NW[0ZoM6RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkG1NVE6PDVpPkKxOVEyQTR3PD;hQi=>
HEK293 NF\tToxHfW6ldHnvckBie3OjeR?= MUnJcohq[mm2aX;uJI9nKE2UUEStcYVlcWG2ZXSgSVIuOTekZYThS{B1emGwc4DvdpQhcW5iaIXtZY4hVVKSNDDlfJBz\XO|aX7nJGhGUzJ7MzDj[YxteyCrbjDwdoV{\W6lZTDv[kAxNjZidH:gOUB2VSCHMj2xO4JmfGGJ MV28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTVzMUm0OUc,OjF3MUG5OFU9N2F-
HEK M3fFeGZ2dmO2aX;uJIF{e2G7 NFjHfHZFcXOybHHj[Y1mdnRib3[gX|NJZUOSLUW1PVQxKG[{b32gbJVu[W5icnXjc41jcW6jboSgR2IyKHKnY3XweI9zKGW6cILld5Nm\CCrbjDISWsh[2WubIOsJGtqRTBwMEGy{txO M1nIVVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzN{CyOFk5Lz5{MUewNlQ6QDxxYU6=
HEK MVHGeY5kfGmxbjDhd5NigQ>? NVe4ZXFYTGm|cHzhZ4Vu\W62IH;mJHs{UF2FUD21OVk1OCCocn;tJIh2dWGwIILlZ49u[mmwYX70JGNDOiC{ZXPldJRweiCneIDy[ZN{\WRiaX6gTGVMKGOnbHzzMEBMcT1yLke5{txO M13mO|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzN{CyOFk5Lz5{MUewNlQ6QDxxYU6=
CHO Mlv1SpVv[3Srb36gZZN{[Xl? MorUNUBpeg>? MmDRSIl{eGyjY3Xt[Y51KG:oIGuzTH1EWDV3OUSwJIZzd21iaIXtZY4h[2GwbnHibY5wcWRiQ1KyJJJm[2WydH;yJIV5eHKnc4Pl[EBqdiCFSF:gZ4VtdHNiYYSgdGghPy52IHHmeIVzKDFiaIKgZpkhdGmzdXnkJJNkcW62aXzsZZRqd25iY3;1cpRqdmduIFnDOVA:OS57ON88US=> NV7kcoFnRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkG3OFE5OzVpPkKxO|QyQDN3PD;hQi=>
HEK293 NIq2UWRHfW6ldHnvckBie3OjeR?= NVvPXWVyPSCvaX7z NIrHN3ZKdmirYnn0bY9vKG:oIHj1cYFvKEWURzDlfJBz\XO|ZXSgbY4hUEWNMkmzJINmdGy|IHHzd4V{e2WmIHHzJIlvcGmkaYTpc44hd2ZicH;0ZZN{cXWvIHPoZY5v\WxiY4XydoVvfCCjZoTldkA2KG2rboOgZpkheGG2Y3igZ4xidXBiYYPzZZktKEmFNUC9Nk44Qc7:TR?= NXTKZW5wRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkG3OFE5OzVpPkKxO|QyQDN3PD;hQi=>
CHO MW\GeY5kfGmxbjDhd5NigQ>? MY[5NEBucW6| MlPpSIl{eGyjY3Xt[Y51KG:oIGuzTH1DVVNvN{K1OVE6KG[{b32gbJVu[W5iQ1KxJJJm[2WydH;yJIV5eHKnc4Pl[EBqdiCFSF:gZ4VtdHNiYX\0[ZIhQTBibXnud{BjgSC|Y3nueIltdGG2aX;uJINwfW62aX7nMEBMcT1yLkCwNFc{|ryP Ml3lQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF7NkK1O|UoRjJzOU[yOVc2RC:jPh?=
CHO-K1 MVHGeY5kfGmxbjDhd5NigQ>? MoL4RY51[WexbnnzeEBi[3Srdnn0fUBifCCqdX3hckBESjFicnXj[ZB1d3JiZYjwdoV{e2WmIHnuJGNJVy2NMTDj[YxteyClbz3lfJBz\XO|aX7nJGdidHCqYYGxOkBie3Onc4Pl[EBieyCrbnjpZol1cW:wIH;mJGNRPTV7NECtbY5lfWOnZDDpcpRz[WOnbHz1cIFzKGOjbHPpeY0hdW:kaXzpfoF1cW:wIHL5JIZtfW:{b33leJJ6NCCNZU2wMlAxOTIQvF2= NVP4N41mRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKzO|I5OzVpPkKyN|czQDN3PD;hQi=>
CHO-K1 M4\DdWZ2dmO2aX;uJIF{e2G7 MYDEbZNxdGGlZX3lcpQhd2ZiW{PIYWNRPTV7NECg[pJwdSCqdX3hckBESjFicnXj[ZB1d3JiZYjwdoV{e2WmIHnuJGNJVy2NMTDj[YxteyxiS3m9NE4xODZ{zszN NGe5OXM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkO3Nlg{PSd-MkKzO|I5OzV:L3G+
CHO-K1 MY\GeY5kfGmxbjDhd5NigQ>? MnL3SIl{eGyjY3Xt[Y51KG:oIGuzTH1EWDV3OUSwJIZzd21iQ1KyJJJm[2WydH;yJIV5eHKnc4Pl[EBqdiCFSF:tT|Eh[2WubIOsJGtqRTBwM{Gz{txO Mn3nQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ|N{K4N|UoRjJ{M{eyPFM2RC:jPh?=
HEK MUfGeY5kfGmxbjDhd5NigQ>? MWHEbZNxdGGlZX3lcpQhd2ZiW{PIYWNRNTV3LEm0NEBnem:vIHj1cYFvKHKnY3;tZolv[W62IFPCNUBz\WOncITvdkB1emGwc3\lZ5Rm\CCrbjDISWsh[2WubIOsJGtqRTBwMEGy{txO NY\nWlJZRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkK1OFg1PTdpPkKyOVQ5PDV5PD;hQi=>
HEK M2nEbmZ2dmO2aX;uJIF{e2G7 NGDvOHZFcXOybHHj[Y1mdnRib3[gX|NJZUOSLUW1MFk1OCCocn;tJIh2dWGwIILlZ49u[mmwYX70JGNDOiC{ZXPldJRweiC2cnHud4Zm[3SnZDDpckBJTUtiY3XscJMtKEurPUCuO|nPxE1? M4HpPVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{NUS4OFU4Lz5{MkW0PFQ2PzxxYU6=
CHO NGrtOmlHfW6ldHnvckBie3OjeR?= MWiyJIhzew>? M3G3U2Rqe3CuYXPlcYVvfCCxZjDbN2heS1B3NTy5OFAh\nKxbTDoeY1idiCFQkGgdoVk\XC2b4Kg[ZhxemW|c3XkJIlvKEOKTzDj[YxteyCjZoTldkAzKGi{czDifUBtcXG3aXSgd4NqdnSrbHzheIlwdiClb4XueIVzNCCNaU2wMlAyOjcQvF2= MXS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjlzNkewO{c,OjJ7MU[3NFc9N2F-
CHO NWHTVZBwTnWwY4Tpc44h[XO|YYm= NWrqUGE4OiCqcoO= NGm4em9FcXOybHHj[Y1mdnRib3[gX|NJZUOSNUWsPVQxKG[{b32gbJVu[W5iQ1KyJJJm[2WydH;yJIV5eHKnc4Pl[EBqdiCFSF:gZ4VtdHNiYX\0[ZIhOiCqcoOgZpkhdGmzdXnkJJNkcW62aXzsZZRqd25iY3;1cpRmeixiS3m9NE46|ryP M2T0R|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{OUG2O|A4Lz5{MkmxOlcxPzxxYU6=
CHO M{TqRmZ2dmO2aX;uJIF{e2G7 NVPIS2tPUW64ZYLz[UBi\2:waYP0JIFkfGm4aYT5JIFo[Wmwc4SgR2IyKHKnY3XweI9zKGW6cILld5Nm\CCrbjDoeY1idiCFSF:gZ4VtdHNiYYPz[ZN{\WRiYYOg[YZn\WO2IH;uJIZwenOtb3zpck1{fGmvdXzheIVlKGODTWCgcIV3\WxuIFnDOVA:OC5yNUJOwG0> MnzGQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ7NUmyOFkoRjJ{OUW5NlQ6RC:jPh?=
CHO NGDZU3RHfW6ldHnvckBie3OjeR?= M4jIO|EhcHJ? M{TPXGRqe3CuYXPlcYVvfCCxZjDbN2heS1B3NUm0NEBnem:vIHj1cYFvKEOEMTDy[YNmeHSxcjDlfJBz\XO|ZXSgbY4hS0iRIHPlcIx{KGmwY4XiZZRm\CCob4KgNUBpeixiS3m9NE4xOTB4zszN NWO1NppuRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkOwO|I{OzlpPkKzNFczOzN7PD;hQi=>
CHO MkDaSpVv[3Srb36gZZN{[Xl? NYOxflJ5RiByLkGgcm0> NGL1Wo0yKGi{ M1rKXWlvfmW{c3WgZYdwdmm|dDDhZ5Rqfmm2eTDheEBpfW2jbjDy[YNwdWKrbnHueEBESjFicnXj[ZB1d3JidILhcpNn\WO2ZXSgbY4hS0iRIHPlcIx{KGG|c3Xzd4VlKGG|IILl[JVkfGmxbjDv[kBcOzWVXVfUVIdidW2jUzDibY5lcW6pIHH0JF4hOC5zIH7NJIFnfGW{IEGgbJIh[nlibHnxeYllKHOlaX70bYxt[XSrb36gd5Bm[3S{b33leJJ6 MnTiQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN|NUezNFcoRjJ|M{W3N|A4RC:jPh?=
N1E-115 MWXGeY5kfGmxbjDhd5NigQ>? M4XUSFEhfU1? M{DxS|UhdWmwcx?= MoX6TY53\XK|ZTDh[49vcXO2IHHjeIl3cXS7IHH0JGNDOSC{ZXPldJRweiCrbjDtc5V{\SCQMVWtNVE2KGOnbHzzJIF{e2W|c3XkJIF{KGmwaHnibZRqd25ib3[gW2lPKDV3LEKxNk0zNWmwZIXj[YQhTVKNMT:yJJBpd3OyaH;yfYxifGmxbjDheEAyKHWPIITy[YF1\WRiNTDtbY5{KHC{aX;yJJRwKFeLTjC1OUwzOTJvMjDjbIFtdGWwZ3WgZpkhX2W|dHXyckBjdG:2IHHuZYx6e2m| M1vNW|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|M{W3N|A4Lz5{M{O1O|MxPzxxYU6=
CHO MoexSpVv[3Srb36gZZN{[Xl? MlPKRY51[WexbnnzeEBi[3Srdnn0fUBifCCqdX3hckBIWFJzODD0doFve2[nY4Tl[EBqdiCFSF:gZ4VtdHNiYYPz[ZN{\WRiYYOg[IVtfGF7LWTIR{1qdmS3Y3XkJIJmfGFvYYLy[ZN1cW5icnXjdpVqfG2nboSgbY5kfWKjdHXkJFYxKG2rboOgdJJqd3JidH:g[IVtfGF7LWTIR{Bi\GSrdHnvckBjgSCkZYThMYFzemW|dHnuJJRz[W6|bH;jZZRqd25iYYPzZZktKEmFNUC9NVAvOc7:TR?= NGDpdmc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{[3PVk2PSd-MkO2O|k6PTV:L3G+
HEK MXTGeY5kfGmxbjDhd5NigQ>? NILvOG4yKGi{ NXzOfYVqSW62YXfvcol{fCCjY4Tpeol1gSCjdDDoeY1idiCFQkGgdoVk\XC2b4Kgc5ZmemW6cILld5Nm\CCrbjDISWsh[2WubIOgZZN{\XO|ZXSgZZMhYzN3U23HWHBo[W2vYTDibY5lcW6pIHHmeIVzKDFiaIKgZpkhdGmzdXnkJJNkcW62aXzsZZRqd25iY3;1cpRqdmdiYX7hcJl{cXNuIFXDOVA:OC5yMEG1{txO M4HqclxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MUe1OVczLz5{NEG3OVU4OjxxYU6=
CHOK1 NGPHdGNHfW6ldHnvckBie3OjeR?= M{LzPVEhcHJ? M332OGRqe3CuYXPlcYVvfCCxZjDbN2heS1B3NUm0NEBnem:vIHj1cYFvKEOEMTDy[YNmeHSxcjDlfJBz\XO|ZXSgbY4hS0iRS{GgZ4VtdHNiYX\0[ZIhOSCqcjDifUBtcXG3aXSgd4NqdnSrbHzheIlwdiClb4XueIlv\yCjbnHsfZNqeyxiS3m9NE4xODV7zszN NGm5Zno9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEG3OVU4Oid-MkSxO|U2PzJ:L3G+
CHO MXLGeY5kfGmxbjDhd5NigQ>? NIr3Smg1PSCvaX7z Mn3SRY51[WexbnnzeEBi[3Srdnn0fUBifCCqdX3hckBESjFicnXj[ZB1d3Jic4ThZox6KGW6cILld5Nm\CCrbjDDTG8h[2WubIOgZ48u\XiycnXzd4lv\yClbz3lfJBz\XO|aX7nJGdiOTVxMU[gZZN{\XO|ZXSgZZMh[2GuY3n1cUBkfXK{ZX70JIFnfGW{IES1JI1qdnNiYomg[ox2dy12IFHNJIF{e2G7LDDJR|UxRTBwMEGz{txO NFqySoU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NES0OVMyOCd-MkS0OFU{OTB:L3G+
CHO NHT2VFdHfW6ldHnvckBie3OjeR?= MnfLOFUhdWmwcx?= NX\2eowzSW62YXfvcol{fCCjY4Tpeol1gSCjdDDDRlIhemWlZYD0c5IhMHWwa37ve44hd3KrZ3nuLUB{fGGkbImg[ZhxemW|c3XkJIlvKEOKTzDj[YxteyClbz3lfJBz\XO|aX7nJINwNWW6cILld5NqdmdiR3GxOU8yPiCjc4Pld5Nm\CCjczDjZYxkcXWvIHP1dpJmdnRiYX\0[ZIhPDVibXnud{BjgSCobIXvMVQhSU1iYYPzZZktKEmFNUC9PU45|ryP NVOyd4Z{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS0OFU{OTBpPkK0OFQ2OzFyPD;hQi=>
CHO-K1 M1\0UGZ2dmO2aX;uJIF{e2G7 Mk\sNVAhdWmwcx?= NGfndlBCdnSjZ3;ubZN1KGGldHn2bZR6KGG2IHj1cYFvKEOEMTDy[YNmeHSxcjDlfJBz\XO|ZXSgbY4hS0iRLVuxJINmdGy|IHHzd4V{e2WmIHHzJIlvcGmkaYTpc44hd2ZiQ2CtOVU6PDBvaX7keYNm\CCdM{XTYWdVWGejbX3hV{BjcW6maX7nJIlv[3WkYYTl[EBnd3JiMUCgcYlveyCycnnvdkB1dyCFUD21OVk1OC2laHHscIVv\2VibXXhd5Vz\WRiYX\0[ZIhOSCqcjDifUBj\XSjIHPveY51cW6pLDDLbV0xNjByMUdOwG0> MVm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDlyMES4OEc,OjR7MEC0PFQ9N2F-
HEK293 NEXyOlJHfW6ldHnvckBie3OjeR?= NFrqVo03OCCvaX7z NXT0RoV6TGm|cHzhZ4Vu\W62IH;mJHs{UF2VUkG0NVcyPkFiZn;ycUBpfW2jbjDDRlEhemWlZYD0c5Ih\XiycnXzd4VlKGmwIFjFT|I6OyClZXzsd{Bi\nSncjC2NEBucW6|IHL5JIJmfGFiY3;1cpRqdmduIFvpQVAvODBzON88US=> Mn3XQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR7MEC0PFQoRjJ2OUCwOFg1RC:jPh?=
CHO-K1 M3XjdGZ2dmO2aX;uJIF{e2G7 MUK2NEBucW6| M2DvPGRqe3CuYXPlcYVvfCCxZjDbN2heS1BvNUW5OFAh\nKxbTDoeY1idiCFQkKgdoVk\XC2b4Kg[ZhxemW|c3XkJIlvKEOKTz3LNUBk\WyuczDh[pRmeiB4MDDtbY5{KGK7IHLleIEh[2:3boTpcoctKEurPUCuOVIz|ryP NFLEdZA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEmwNFQ5PCd-MkS5NFA1QDR:L3G+
CHO M1q0fGZ2dmO2aX;uJIF{e2G7 NUT2N2R1OiCqcoO= NEfzZVNFcXOybHHj[Y1mdnRib3[gX|NJZUOSNUWsPVQxKG[{b32gdoVkd22kaX7hcpQhcHWvYX6gR2IyKHKnY3XweI9zKGW6cILld5Nm\CCrbjDDTG8h[2WubIOgZYZ1\XJiMjDodpMh[nlibHnxeYllKHOlaX70bYxt[XSrb36gZ492dnSrbnesJGtqRTBwMEGyOu69VQ>? MnjpQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR7MEC1OlEoRjJ2OUCwOVYyRC:jPh?=
CHO NH\yfXRHfW6ldHnvckBie3OjeR?= NEfFb3ozKGi{cx?= NH6wUFVFcXOybHHj[Y1mdnRib3[gX|NJZUOSNUWsPVQxKG[{b32gdoVkd22kaX7hcpQhcHWvYX6gR2IzKHKnY3XweI9zKGW6cILld5Nm\CCrbjDDTG8h[2WubIOgZYZ1\XJiMjDodpMh[nlibHnxeYllKHOlaX70bYxt[XSrb36gZ492dnSrbnesJGtqRTBwOd88US=> M1LRRVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OUCwOVYyLz5{NEmwNFU3OTxxYU6=
CHO MXXGeY5kfGmxbjDhd5NigQ>? MWq5NEBucW6| NIjlfHNC\2:waYP0JIFkfGm4aYT5JIF1KEeSUkW1JEh2dmuwb4fuJI9zcWerbjmg[ZhxemW|c3XkJIlvKEOKTzDj[YxteyCjc4Pld5Nm\CCjczDpcohq[mm2aX;uJI9nKEySST3pcoR2[2WmIHLleIEu[XK{ZYP0bY4hfHKjboPsc4NifGmxbjDh[pRmeiB7MDDtbY5{KGK7IHz1cYlv\XOlZX7j[UBie3OjeTygSWM2OD1{LkCx{txO NYKyNmttRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS5NFA2PjFpPkK0PVAxPTZzPD;hQi=>
RD-HGA16 NV3zVYNqTnWwY4Tpc44h[XO|YYm= M2X1bmFvfGGpb37pd5Qh[WO2aY\peJkh[XRiQ1KxMW9ZOSCqZYTldo9lcW2ncjCoeY5sdm:5bjDvdolocW5rIHX4dJJme3OnZDDpckBTTC2KR1GxOkBk\WyuczDhd5Nme3OnZDDhd{BqdmirYnn0bY9vKG:oIH;y[ZhqdiCDLXnu[JVk\WRiY3HsZ4l2dSCvb3LpcIl7[XSrb36gZpkh\my3b4LvcYV1emmlIHntZYdqdmdicHzheIUhemWjZHXyJIFv[Wy7c3nzMEBM\T1yLkCwNe69VQ>? NFjqdY49[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEm0OFc{PCd-MkS5OFQ4OzR:L3G+
RD-HGA16 MlzXSpVv[3Srb36gZZN{[Xl? NUnvfGU{SW62YXfvcol{fCCjY4Tpeol1gSCjdDDDRlEhemWlZYD0c5IhMHWwa37ve44hd3KrZ3nuLUBmgHC{ZYPz[YQhcW5iUlStTGdCOTZiY3XscJMh[XO|ZYPz[YQh[XNiaX7obYJqfGmxbjDv[kBEWDV3OUSwMYlv\HWlZXSgZ4Ft[2m3bTDtc4JqdGm8YYTpc44h[nliZnz1c5JwdWW2cnnjJIlu[WerbnegdIxifGVicnXh[IVzKGGwYXz5d4l{NCCNZU2wMlAxOTIQvF2= M1HjOlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OUS0O|M1Lz5{NEm0OFc{PDxxYU6=
Sf9 MkH5SpVv[3Srb36gZZN{[Xl? M4[1XFIxKG2rboO= M1nyRWlvfmW{c3WgZYdwdmm|dDDhZ5Rqfmm2eTDheEBpfW2jbjDDRlEhemWlZYD0c5Ih\XiycnXzd4VlKGmwIGPmPUBk\WyuczDjc4V5eHKnc4PpcochT2KndHGx[4FudWF{IHHu[EBTW0d2IHHzd4V{e2WmIHHzJIRm\3KjZHH0bY9vKG:oIGvnZY1u[S1|M2DdS3RRKGGodHXyJFIxKG2rboOgZpkhe3SnYXT5MZN1[XSnIFfUVIF{\SCjc4PhfUwhTUN3ME2wMlA2|ryP NFTrNVQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUC5OlI6Pyd-MkWwPVYzQTd:L3G+
Sf9 NXrlZXNMTnWwY4Tpc44h[XO|YYm= M1nk[FIxKG2rboO= M1\VXWlvfmW{c3WgZYdwdmm|dDDhZ5Rqfmm2eTDheEBpfW2jbjDDRlEhemWlZYD0c5Ih\XiycnXzd4VlKGmwIGPmPUBk\WyuczDjc4V5eHKnc4PpcochT2KndHGx[4FudWF{IHHu[EBTW0d2IHHzd4V{e2WmIHHzJIRm\3KjZHH0bY9vKG:oIGvnZY1u[S1|M2DdS3RRKGGodHXyJFIxKG2rboOgZpkhe3SnYXT5MZN1[XSnIFfUVIF{\SCjc4PhfUwhTUN3ME2wMlA2ODF{zszN NGnhS2o9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUC5OlI6Pyd-MkWwPVYzQTd:L3G+
CHO M3LDOGZ2dmO2aX;uJIF{e2G7 NYO5bo9ESW62YXfvcol{fCCjY4Tpeol1gSCjZ3HpcpN1KEOEMWKgLJVvc26xd36gc5Jq\2mwKTDDTG8h[2WubIOgd5Ri[my7IHX4dJJme3OrbnegS4FteGijMU[gZZN{\XO|ZXSgZZMhcW6qaXLpeIlwdiCxZjDDVFU2QTRyLXnu[JVk\WRiaX7jdoVie2ViaX6gbY51emGlZXzseYxieiClYXzjbZVuKGyndnXsJJBz\S22cnXheIVlKDFyIH3pcpMh[mWob4LlJGNRPTV7NECgd5RqdXWuYYTpc44h[nlibXnjdo9xdGG2ZTDy[YFl\XJiYnHz[YQh[XO|YYmsJGlEPTB;MD6wNVM2|ryP NHLMNoM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkG1NVI{OSd-Mk[xOVEzOzF:L3G+
CHO NWjnOodNTnWwY4Tpc44h[XO|YYm= M4f5XmFvfGGpb37pd5Qh[WO2aY\peJkh[WejaX7zeEBESjKUIDj1cotvd3ewIH;ybYdqdiliQ1jPJINmdGy|IIP0ZYJtgSCneIDy[ZN{cW6pIFfhcJBp[TF4IHHzd4V{e2WmIHHzJIlvcGmkaYTpc44hd2ZiQ2C1OVk1OC2rbnT1Z4VlKGmwY4LlZZNmKGmwIHnueJJi[2WubIXsZZIh[2GuY3n1cUBt\X[nbDDwdoUufHKnYYTl[EAyOCCvaX7zJIJm\m:{ZTDDVFU2QTRyIIP0bY12dGG2aX;uJIJ6KG2rY4LvdIxifGVicnXh[IVzKGKjc3XkJIF{e2G7LDDJR|UxRTlwMd88US=> M2TDTlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MUWxNlMyLz5{NkG1NVI{OTxxYU6=
HEK293 MojISpVv[3Srb36gZZN{[Xl? MVHJcY1m\GmjdHWgZY51[WexbnnzeE9Kdn[ncoPlJIFod26rc4SgZYN1cX[rdImgZZQhcGWvYXfncJV1cW6rbj30ZYdo\WRiaIXtZY4hS0JzIILlZ4VxfG:{IHX4dJJme3OnZDDpckBJTUt{OUOgZ4VtdHNiYYPz[ZN{\WRiYYOgdoV3\XK|YXygc4YhOSC3TTDDVFU2NDl2MD3pcoR2[2WmIHnubIljcXSrb36gc4YhPSC3TTDmc5J{c2:uaX6tbY5lfWOnZDDjRW1RKGGlY4XteYxifGmxbjDifUBscW6ndHnjJINCVVBiYYPzZZk> MmjoQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ{MEO2OVgoRjJ4MkCzOlU5RC:jPh?=
HEK293 MomxSpVv[3Srb36gZZN{[Xl? MorDPVAhdWmwcx?= NEX6cI1FcXOybHHj[Y1mdnRib3[gX|NJZS2FUD21OVk1OCCocn;tJIh2dWGwIILlZ49u[mmwYX70JGNDOSC{ZXPldJRweiCneIDy[ZN{\WRiaX6gTGVMOjl|IHPlcIx{KGGodHXyJFkxKG2rboOgZpkhS2:vcHX0bZRqd25iYnnu[Ilv\yCjc4PhfUwhU2mncU2wMlAyOs7:TR?= MX:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjd3NkC5O{c,OjZ5NU[wPVc9N2F-
HEK293 MoPpSpVv[3Srb36gZZN{[Xl? NHKweo46OCCvaX7z NIfqRWxFcXOybHHj[Y1mdnRib3[gX|NJZS2FUD21OVk1OCCocn;tJIh2dWGwIILlZ49u[mmwYX70JGNDOiC{ZXPldJRweiCneIDy[ZN{\WRiaX6gTGVMOjl|IHPlcIx{KGGodHXyJFkxKG2rboOgZpkhS2:vcHX0bZRqd25iYnnu[Ilv\yCjc4PhfUwhU2mncU2wMlc6|ryP NHjrb|Q9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{Nke1OlA6Pyd-Mk[3OVYxQTd:L3G+
CHO-K1 NYnPOXZXTnWwY4Tpc44h[XO|YYm= MlPxRY51[WexbnnzeEBi[3Srdnn0fUBifCCqdX3hckBESjFicnXj[ZB1d3JiZYjwdoV{e2WmIHnuJGNJVy2NMTDj[YxteyCjc4Pld5Nm\CCjczDpcohq[mm2aX;uJI9nKEOSNUW5OFAucW6mdXPl[EBqdnS{YXPlcIx2dGG{IHPhcINqfW1ibX;ibYxqgmG2aX;uJIJ6KEOjbHPlbY4uPCCDTT3zeIFqdmmwZzDiZZNm\CCITFnQVkBie3OjeTygT4U:OC5yMEGx{txO MkfSQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ6MkexN|coRjJ4OEK3NVM4RC:jPh?=
CHO Mle3SpVv[3Srb36gZZN{[Xl? M4\aPFkxKHOnY4O= NWPPW4djUW64ZYLz[UBi\2:waYP0JIFkfGm4aYT5JIF1KGi3bXHuJGNDOSC{ZXPldJRweiCneIDy[ZN{\WRiaX6gR2hQKGOnbHzzJIF{e2W|c3XkJIF{KGmwY4LlZZNmKGmwIHnueJJi[2WubIXsZZIh[2GuY3n1cUBud2KrbHn6ZZRqd25iYX\0[ZIhQTBic3Xjd{BjgSCFYXzj[YlvNTRiQV2td5RicW6rbnegZoF{\WRiRlzJVHIh[XO|YYmsJGVEPTB;MD6wNFXPxE1? MYK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjh{N{GzO{c,OjZ6MkexN|c9N2F-
SJ-GBM2 M4e1dJFJXFNiYYPzZZk> NXO0c5VReUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IGPKMWdDVTJiY3XscJM> MWq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
A673 MnXudWhVWyCjc4PhfS=> NFjpfXJyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiQU[3N{Bk\Wyucx?= Mkn1QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
SK-N-MC MmewdWhVWyCjc4PhfS=> M4mxNZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCVSz3OMW1EKGOnbHzz Ml7KQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
BT-37 MUDxTHRUKGG|c3H5 MWjxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhSlRvM{egZ4VtdHN? Mk\1QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
SK-N-SH MkfxdWhVWyCjc4PhfS=> M{mxSJFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCVSz3OMXNJKGOnbHzz MkjCQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
NB1643 MmLhdWhVWyCjc4PhfS=> NV6zZotUeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IF7CNVY1OyClZXzsdy=> NVfQWoQ5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
LAN-5 MnvkdWhVWyCjc4PhfS=> NV\SelA6eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IFzBUk02KGOnbHzz NWfjcllqRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
BT-12 NGDZdnhyUFSVIHHzd4F6 MYjxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhSlRvMUKgZ4VtdHN? MXS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
OHS-50 NVPmWmR4eUiWUzDhd5NigQ>? M2\NXpFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCRSGOtOVAh[2WubIO= MkezQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
RD NWL4TYJWeUiWUzDhd5NigQ>? MUHxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhWkRiY3XscJM> NIfMblI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
A673 M{i3TZFJXFNiYYPzZZk> MkTIdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[|ohS2:wZnnycYF1d3K7IIPjdoVmdiCob4KgRVY4OyClZXzsd{k> NYLS[pk1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
SK-N-MC MXTxTHRUKGG|c3H5 NFrPcZByUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBUUy2QLV3DJINmdGy| NXP2T2JjRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
DAOY Ml7MdWhVWyCjc4PhfS=> MXrxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBEd26oaYLtZZRwenlic3Py[YVvKG[xcjDERW9[KGOnbHzz NIDhU|k9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
TC32 M{PybZFJXFNiYYPzZZk> NGjneIlyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBVSzN{IHPlcIx{ NWnRRYFlRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
U-2 OS NEflPYVyUFSVIHHzd4F6 MY\xTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBEd26oaYLtZZRwenlic3Py[YVvKG[xcjDVMVIhV1NiY3XscJM> MlzOQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
Rh41 NHzPUJByUFSVIHHzd4F6 NIrpOJhyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBTcDRzIHPlcIx{ NW[2[2FqRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
Saos-2 NGTzO4VyUFSVIHHzd4F6 NGjDSZhyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBU[W:|LUKgZ4VtdHN? NXXkSYVpRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
CHOK1 M2\OXGZ2dmO2aX;uJIF{e2G7 MYK5NEBucW6| MnHXTY53\XK|ZTDh[49vcXO2IHHjeIl3cXS7IHH0JGMufGW{bXnuZYxtgSCycn;sbY5sNXSjZ3fl[EBud3W|ZTDDRlIhemWlZYD0c5Ih\XiycnXzd4VlKGmwIFPIU2syKGOnbHzzJIhiemKxcnnu[{Bj\XSjLXfhcIFkfG:|aXThd4Uh\W68eX3lJIZ2e2WmIHLleIEu[XK{ZYP0bY4h[XO|ZYPz[YQh[XNiaX7jdoVie2ViaX6gZoV1[S2jcoLld5RqdiC{ZXPyeYl1dWWwdDDh[pRmeiB7MDDtbY5{KGK7IHPo[Y1qdHWvaX7ld4NmdnRiYYPzZZktKEWFNUC9NE4xOTYQvF2= M2nlfFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7OUO5O|Q1Lz5{OUmzPVc1PDxxYU6=
HEK293 NVHjNFI2TnWwY4Tpc44h[XO|YYm= Ml7sRY51[WexbnnzeEBi[3Srdnn0fUBifCCqdX3hckBESjFicnXj[ZB1d3JiZYjwdoV{e2WmIHnuJGhGUzJ7MzDj[YxteyCkeTDHWHBo[W2vYWOgZolv\GmwZzDhd5NigSxiS3W9NE4xODB{zszN MV:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{ODB5N{[wPUc,OzByN{e2NFk9N2F-
HEK293 NVjwd21mTnWwY4Tpc44h[XO|YYm= MX65NEB{\WO| MWXJcpZmenOnIHHnc45qe3RiYXP0bZZqfHliYYSgbJVu[W5iQ1KxJJJm[2WydH;yJIV5eHKnc4Pl[EBqdiCKRVuyPVMh[2WubIOgZ48u\XiycnXzd4lv\yCJYXzwbIFyOTZiYYPz[ZN{\WRiYYOgbY5pcWKrdHnvckBw\iClYXzjbZVuKG2xYnnsbZpifGmxbjDh[pRmeiB7MDDz[YN{KGK7IHPhcINmcW5vNDDBRW0h\HmnLXLhd4VlKE[OSWDSJIF{e2G7LDDFR|UxRTBwNUi2{txO M3z1clxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzNyMEe3OlA6Lz5|MEC3O|YxQTxxYU6=
HEK293 NYftVJhvTnWwY4Tpc44h[XO|YYm= M1PqNFMxKG2rboO= M1TabWlvfmW{c3WgZYdwdmm|dDDhZ5Rqfmm2eTDheEBpfW2jbjDDRlEhemWlZYD0c5Ih\XiycnXzd4VlKGmwIFjFT|I6OyClZXzsd{Bie3Onc4Pl[EBieyCrbnjpZol1cW:wIH;mJIZwenOtb3zpck1qdmS3Y3XkJINCVVBiYXPjeY12dGG2aX;uJIFnfGW{IEOwJI1qdnNiYomgTHRTTiCjc4PhfUwhTUN3ME2wMlAxPDIQvF2= NIP5eVM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9|MEOzPVM5Pyd-M{CzN|k{QDd:L3G+
CHO NEHEV|BHfW6ldHnvckBie3OjeR?= NFzsVGJFcXOybHHj[Y1mdnRib3[gX|NJZS2FUEW1PVQxKG[{b32gbJVu[W5icnXjc41jcW6jboSgZ4FvdmGkaX7vbYQhS0JzIILlZ4VxfG:{IHX4dJJme3OnZDDpckBEUE9iY3XscJMh[nlicnHkbY9tcWejbnSgZolv\GmwZzDhd5NigSxiS3m9NE4yPDQQvF2= NHPNblg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9|MU[wPVYxQCd-M{G2NFk3ODh:L3G+
CHO MXnGeY5kfGmxbjDhd5NigQ>? Ml;FRYdwdmm|dDDhZ5Rqfmm2eTDheEBpfW2jbjDHVHI2PSCneIDy[ZN{\WRiaX6gR2hQKGOnbHzzJIF{e2W|c3XkJIF{KGmwZIXjeIlwdiCxZjDMVGkucW6mdXPl[EBj\XSjLXHydoV{fGmwIILlZ5J2cXSvZX70JIJ6KGKndHGt[4Ft[WO2b4Pp[IF{\SCnbor5cYUh\nKjZ33lcpQh[2:vcHzlcYVvfGG2aX;uJI1mfGixZDygSWM2OD1{LkCx{txO NHLMVpI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOTFxJ{7DbGVOSkx:L3G+
CHO MlHjSpVv[3Srb36gZZN{[Xl? NUPtPFlTSWexbnnzeEBi[3Srdnn0fUBifCCqdX3hckBIWFJzODDlfJBz\XO|ZXSgbY4hS0iRIHPlcIx{KGG|c3Xzd4VlKGG|IHnu[JVkfGmxbjDv[kBj\XSjLXHydoV{fGmwIILlZ5J2cXSvZX70JIJ6KGKndHGt[4Ft[WO2b4Pp[IF{\SCnbor5cYUh\nKjZ33lcpQh[2:vcHzlcYVvfGG2aX;uJI1mfGixZDygSWM2OD1zMD6x{txO NU\UU45{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTFzLze+R4hGVUKOPD;hQi=>

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
p-LRP6 / LRP6 / Lgr5 ; 

PubMed: 29354056     


Representative Western blot analysis of Lgr5, LRP6 and phosphorylated (Ser1490) LRP6. GAPDH was used as loading control.

β-catenin; 

PubMed: 29354056     


Representative Western blot analysis (left) of β-Catenin in total protein lysates from GTG7 cells. Right, densitometric analysis of β-Catenin normalized vs. GAPDH, used as loading control. Results are expressed as means ± SD of 3 independent experiments performed at least in duplicate (∗∗p < 0.01).

CD44 / Lgr5 / CD133 / EpCAM ; 

PubMed: 29354056     


Representative Western blot analysis of CD44, Lgr5, CD133 and EpCAM in total protein lysates from HCT116 cells. GAPDH was used as loading control.

29354056
Immunofluorescence
Lgr5 ; 

PubMed: 29354056     


Confocal microscopy analysis of Lgr5 (red fluorescence) in GTG7 cells treated with Rimonabant at indicated doses for 18 h. Nuclei were stained with Hoechst (blue fluorescence); GFP (green); Scale bar = 5 μm.

β-catenin; 

PubMed: 29354056     


Confocal microscopy analysis of β-Catenin (red) in GTG7 cells treated with Rimonabant at indicated doses for 18 h. Nuclei were stained with Hoechst (blue fluorescence); GFP (green); Scale bar = 5 μm.

29354056
In vivo

Rimonabant is administered intraperitoneally or orally potently and dose-dependently antagonize classical pharmacological and behavioural effectos of cannabinoid receptor agonists. [3] In the mouse model of azoxymethane-induced colon carcinogenesis, Rimonabant significantly decreased aberrant crypt foci (ACF) formation, which precedes colorectal cancer. [4] Rimonabant (10 mg/kg by gavage) is fed for 2 weeks to 3-month-old male obese Zucker rats as an impaired glucose tolerance model and for 10 weeks to 6-month-old male obese Zucker rats as a model of the metabolic syndrome. RANTES (Regulated upon Activation, Normal T cell Expressed, and Secreted) and MCP-1 (monocyte chemotactic protein-1) serum levels are increased in obese vs lean Zucker rats and significantly reduced by long-term treatment with Rimonabant, which slowes weight gain in rats with the metabolic syndrome. Neutrophils and monocytes are significantly increased in young and old obese vs lean Zucker rats and lowered by Rimonabant. Platelet-bound fibrinogen is significantly enhanced in obese vs lean Zucker rats of both age, and is reduced by Rimonabant. Platelets from obese rats are more sensitive to thrombin-induced aggregation and adhesion to fibrinogen, which are both attenuated by Rimonabant therapy. [5]

Protocol

Kinase Assay:

[1]

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Radioligand Binding Assay:

Human CB1 and CB2 stably transfect HEK 293 cells and cell membrane is purified. 0.2-8 μg of the purified membrane is incubated with 0.75 nM [3H] CP55,940 and Rimonabant in the incubation buffer (50 mM Tris-HCl, 5 mM MgCl2, 1 mM EDTA, 0.3%BSA, pH 7.4). The non-specific binding is defined in the presence of 1 μM of CP55,940. The reactions are incubated for one and a half hours at 30 °C in Multiscreen. The reactions are terminated by manifold filtration and washed four times with ice-cold wash buffer (50mM Tris, pH 7.4, 0.25% BSA).The radioactivity bound to the filters is measured by Topcount. The IC50 is determined as the concentration of Rimonabant required to inhibit 50% of the binding of [3H] CP55,940 and calculated by non-linear regression.
Cell Research:

[2]

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  • Cell lines: Raw 264.7 cells
  • Concentrations: 0,1,4 μM
  • Incubation Time: 17 hours
  • Method:

    Raw 264.7 cells (2 × 106 /well) in 12-well plates are rinsed with PBS and refed culture media supplemented with varying amounts of Rimonabant 1 hour prior to supplementation with 7-ketocholesterol (7KC). All wells are adjusted to receive equal amounts of vehicle. Following 16-hour incubation, caspase-3 and caspase 3-like activity are determined using a fluorogenic substrate (Ac-DEVD-AFC) and a spectrofluorometer equipped with a microplate reader.


    (Only for Reference)
Animal Research:

[3]

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  • Animal Models: Male mice and male rats
  • Dosages: 20 ml/kg (mice) and 5 ml/kg (rats)
  • Administration: Rimonabant is administered i.p. (30 minutes) or p.o. (1hour) before the i.v. injection of WIN55212-2.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 25 mg/mL (53.9 mM)
Water Insoluble
Ethanol '''''2 mg/mL
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
5% DMSO+40% PEG 300+5% Tween 80+dd H2O
For best results, use promptly after mixing.
5 mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 463.79
Formula

C22H21Cl3N4O

CAS No. 168273-06-1
Storage powder
in solvent
Synonyms N/A
Smiles CC1=C(N(N=C1C(=O)NN2CCCCC2)C3=C(C=C(C=C3)Cl)Cl)C4=CC=C(C=C4)Cl

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
Dosage mg/kg Average weight of animals g Dosing volume per animal ul Number of animals
Step 2: Enter the in vivo formulation ()
% DMSO % % Tween 80 % ddH2O
CalculateReset

Bio Calculators

Molarity Calculator

Molarity Calculator

Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

Mass (mg) = Concentration (mM) × Volume (mL) × Molecular Weight (g/mol)

  • Mass
    Concentration
    Volume
    Molecular Weight

*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and SDS / COA (available on product pages).

Dilution Calculator

Dilution Calculator

Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

Concentration (start) x Volume (start) = Concentration (final) x Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

  • C1
    V1
    C2
    V2

* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and SDS / COA (available online).

The Serial Dilution Calculator Equation

  • Serial Dilutions

  • Computed Result

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):
Molecular Weight Calculator

Molecular Weight Calculator

Enter the chemical formula of a compound to calculate its molar mass and elemental composition:

Total Molecular Weight: g/mol

Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT00750347 Completed Drug: Rimonabant and Paracetamol and placebo Pain University Hospital Clermont-Ferrand September 2008 Phase 1
NCT00656487 Completed Drug: rimonabant|Drug: placebo Cannabis Dependence|Cannabis Withdrawal The Scripps Research Institute|National Institute on Drug Abuse (NIDA) April 30 2008 Phase 2
NCT00546325 Completed Drug: Rimonabant|Drug: Placebo Diabetes Mellitus Type 2 Sanofi October 2007 Phase 3
NCT00525681 Completed Drug: cyclosporine A|Drug: tacrolimus Renal Transplantation University of Oslo School of Pharmacy September 2007 Phase 4
NCT00584389 Terminated Drug: rimonabant|Behavioral: Dietary intervention Obesity University of Surrey|European Foundation for the Study of Diabetes|Royal Surrey County Hospital NHS Foundation Trust July 2007 Phase 4
NCT01041170 Completed Drug: THC|Drug: Rimonobant|Drug: Rimonabant Cannabis|Dependence National Institute on Drug Abuse (NIDA)|National Institutes of Health Clinical Center (CC) April 16 2006 Phase 1

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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Cannabinoid Receptor Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID