Quisinostat (JNJ-26481585) 2HCl

Name: Quisinostat (JNJ-26481585) 2HCl
Brand: Selleck Chemicals
SKU: S1096
Rating: 5 (36 reviews)

For research use only.

Catalog No.S1096

36 publications

Quisinostat (JNJ-26481585) 2HCl Chemical Structure

CAS No. 875320-31-3

Quisinostat (JNJ-26481585) 2HCl is a novel second-generation HDAC inhibitor with highest potency for HDAC1 with IC50 of 0.11 nM in a cell-free assay, modest potent to HDACs 2, 4, 10, and 11; greater than 30-fold selectivity against HDACs 3, 5, 8, and 9 and lowest potency to HDACs 6 and 7. Phase 2.

Selleck's Quisinostat (JNJ-26481585) 2HCl has been cited by 36 publications

Cell, 2019, 178(5):1115-1131

PubMed: 31442404 ( click the link to review the publication )

J Clin Oncol, 2016, 10.1200/JCO.2016.66.5547

PubMed: 27507882 ( click the link to review the publication )

Nucleic Acids Res, 2021, 49(4):2390-2399

PubMed: 33544854 ( click the link to review the publication )

Nat Commun, 2020, 29;11(1):2086

PubMed: 32350249 ( click the link to review the publication )

Nucleic Acids Res, 2020, 6;48(6):2912-2923

PubMed: 31970414 ( click the link to review the publication )

Cancers (Basel), 2020, 12(12)E3690

PubMed: 33316946 ( click the link to review the publication )

J Mol Cell Cardiol, 2020, 149:73-81

PubMed: 32971072 ( click the link to review the publication )

Front Cell Dev Biol, 2020, 17;8:235

PubMed: 32363192 ( click the link to review the publication )

Mol Cell Biochem, 2020, 10.1007/s11010-020-03708-8

PubMed: 32146648 ( click the link to review the publication )

Cancer Sci, 2020, 111(7):2374-2384

PubMed: 32391602 ( click the link to review the publication )

Nat Commun, 2019, 10(1):4192

PubMed: 31519896 ( click the link to review the publication )

Neuro Oncol, 2019, 10.1093/neuonc/noz089

PubMed: 31111916 ( click the link to review the publication )

Cell Syst, 2019, 8(2):97-108

PubMed: 30797775 ( click the link to review the publication )

PLoS Comput Biol, 2019, 15(2):e1006826

PubMed: 30785874 ( click the link to review the publication )

ACS Omega, 2019, 4(22):19895-19904

PubMed: 31788622 ( click the link to review the publication )

Cancer Res, 2018, 78(20):5731-5740

PubMed: 30135193 ( click the link to review the publication )

Oncogene, 2018, 37(39):5325-5339

PubMed: 29858601 ( click the link to review the publication )

Oncogene, 2018, 37(50):6414-6424

PubMed: 30068939 ( click the link to review the publication )

Cancer Lett, 2018, 428:160-172

PubMed: 29709701 ( click the link to review the publication )

J Med Chem, 2018, 61(22):10000-10016

PubMed: 30347148 ( click the link to review the publication )

Oncoimmunology, 2018, 7(10):e1484981

PubMed: 30288346 ( click the link to review the publication )

Mol Cancer Ther, 2018, 17(12):2767-2779

PubMed: 30232145 ( click the link to review the publication )

Int J Biol Sci, 2018, 14(13):1845-1858

PubMed: 30443188 ( click the link to review the publication )

J Pathol, 2017, 241(4):534-546

PubMed: 27976373 ( click the link to review the publication )
Cell Death Dis, 2017, 8(6):e2879

PubMed: 28617441 ( click the link to review the publication )

Mol Reprod Dev, 2017, 84(4):340-346

PubMed: 28224725 ( click the link to review the publication )

Int J Parasitol Drugs Drug Resist, 2017, 7(1):51-60

PubMed: 28110187 ( click the link to review the publication )

Cell Death Differ, 2017, 24(1):83-97

PubMed: 27834956 ( click the link to review the publication )

Oncogene, 2016, 35(28):3729-41

PubMed: 26616861 ( click the link to review the publication )

Neurochem Res, 2016, 41(7):1751-60

PubMed: 27220336 ( click the link to review the publication )

Nat Commun, 2015, 6:8648

PubMed: 26468920 ( click the link to review the publication )

Bioorg Med Chem, 2015, 10.1016/j.bmc.2014.12.066

PubMed: 25637120 ( click the link to review the publication )

Oncotarget, 2015, 6(35):37836-51

PubMed: 26473375 ( click the link to review the publication )

J Biol Chem, 2014, 289(28):19519-30

PubMed: 24821725 ( click the link to review the publication )

Nat Commun, 2013, 4:2735

PubMed: 24193185 ( click the link to review the publication )

J Thromb Thrombolysis, 2013, 35(2):185-92

PubMed: 23229086 ( click the link to review the publication )

Purity & Quality Control

Choose Selective HDAC Inhibitors

Biological Activity

Description

Features

An orally bioavailable, second-generation, hydroxamic acid-based HDAC inhibitor.

Targets

HDAC1 ^[1] (Cell-free assay)	HDAC2 ^[1] (Cell-free assay)	HDAC11 ^[1] (Cell-free assay)	HDAC10 ^[1] (Cell-free assay)	HDAC4 ^[1] (Cell-free assay)	View More
0.11 nM	0.33 nM	0.37 nM	0.46 nM	0.64 nM	View More

In vitro

JNJ-26481585 exhibits broad spectrum antiproliferative activity in solid and hematologic cancer cell lines, such as all lung, breast, colon, prostate, brain, and ovarian tumor cell lines, with IC50 ranging from 3.1-246 nM, which is more potent than vorinostat, R306465, panobinostat, CRA-24781, or mocetinostat in various human cancer cell lines tested. ^[1] A recent study shows that JNJ-26481585 promotes myeloma cell death at low nanomolar concentrations by resulting in Mcl-1 depletion and Hsp72 induction. ^[2]

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Activity Description	PMID
A549 cells	NVvH[5J4S2WubDD2bYFjcWyrdImgZZN{[Xl?		M3XXNFI1NCB2ODygc5IhPzJiaB?=	MUT0bIUhUUN3MDD2ZYx2\XNib3[gZ4VtdHNiZn;yJFQ5KGGwZDC3NkBpKG:oIIH1bZNqdm:\|dHH0JJRz\WG2bXXueEB4\XKnIEiyMlQh[W6mIESyMlAhdk1uIILld5Bm[3SrdnXsfU4>	NUK2Zm9WRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMke0NlM1PTRpPkK3OFI{PDV2PD;hQi=>
RH30 cells	NH3PT49HfW6ldHnvckBie3OjeR?=	NV3o[GpQOTVibl2=	NVKzOJh6OjRiaDDhcoQhOzBiaB?=	NGnWZ3RIW0t4OUCgZY5lKEqQSj2yOlQ5OTV6NTDjc49x\XKjdHXkJJRwKGmwZIXj[UBkdGWjdnHn[UBw\iC2aHWgbY5qfGmjdH;yJINie3Cjc3WtPUBqdnSxIHn0d{Bi[3SrdnWgdFM2KGGwZDDwN\|ch\nKjZ33lcpR{KGGwZDDv[kB1cGViZX\m[YN1d3JiY3HzdIF{\S1\|IHnueI8hcXS\|IHHjeIl3\SCyMUKgZY5lKHBzNzDmdoFodWWwdIO=	MnX4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjh4MUe0OFEoRjJ6NkG3OFQyRC:jPh?=
RD cells	M2XrRmZ2dmO2aX;uJIF{e2G7	Mk\3NVUhdk1?	M{\PfFI1KGhiYX7kJFMxKGh?	MXfHV2s3QTBiYX7kJGpPUi1{NkS4NVU5PSClb3;w[ZJifGWmIITvJIlv\HWlZTDjcIVifmGpZTDv[kB1cGViaX7peIlifG:{IHPhd5Bie2VvOTDpcpRwKGm2czDhZ5RqfmVicEO1JIFv\CCyM{eg[pJi\22nboTzJIFv\CCxZjD0bIUh\W[oZXP0c5Ih[2G\|cHHz[U0{KGmwdH:gbZR{KGGldHn2[UBxOTJiYX7kJJAyPyCocnHncYVvfHN?	NETHN2Q9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OE[xO\|Q1OSd-Mki2NVc1PDF:L3G+
HepG2	MXLD[YxtKH[rYXLpcIl1gSCjc4PhfS=>	MlzBOUwhOTBuIEKwMEA1OCxiOECsJFE3OCCjbnSgN\|IxKG6P	MVOyOEwhPDhuIEeyJIg>	M4Tme3Rp\SCLQ{WwJJZidHWnczDv[kBk\WyuczDmc5IheXWrc3nuc5N1[XRidILlZZRu\W62IHH0JFQ5KGGwZDC3NkBpKHencnWgPFEvOiCjbnSgN\|AvQCCwTTygdoV{eGWldHn2[Yx6Ng>?	MYK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQDh2OUC4NEc,Ojh6NEmwPFA9N2F-
HuT78	MmT0SpVv[3Srb36gZZN{[Xl?	NFezZYUyOCCwTR?=		MV;pcoNz\WG\|ZYOgeIhmKGyndnXsJI9nKGGlZYT5cIF1\WRibInzbY5mKEtzMDDv[kBpcXO2b37lJGg{	NXTxdXEzRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxM{CwNVI1OThpPkOwNFEzPDF6PD;hQi=>
Sf9	NUfRTXl7TnWwY4Tpc44h[XO\|YYm=			NGr0fY9KdmirYnn0bY9vKG:oIH\1cIwhdGWwZ4ToJJJm[2:vYnnuZY51KGi3bXHuJGhFSUNzIHX4dJJme3OnZDDpckBj[WO3bH;2bZJ2eyCrbn\lZ5Rm\CCVZkmgZ4VtdHNidYPpcochWkiNSz3BZ{BieyC\|dXLzeJJifGViYomg[ox2d3Knc3PlcoNmKGGwYXz5d4l{NCCLQ{WwJF0hOC5yMECxNUDPxE1w	M{L5OFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ5NkC2OVQ3Lz5{N{[wOlU1PjxxYU6=
Sf9	NILUSXlHfW6ldHnvckBie3OjeR?=			M37vZWlvcGmkaYTpc44hd2ZiZoXscEBt\W6pdHigdoVkd22kaX7hcpQhcHWvYX6gTGRCSzJiZYjwdoV{e2WmIHnuJIJi[3Wub4\pdpV{KGmwZnXjeIVlKFOoOTDj[YxteyC3c3nu[{BTUEuNLVHjJIF{KHO3YoP0doF1\SCkeTDmcJVwemW\|Y3XuZ4Uh[W6jbInzbZMtKEmFNUCgQUAxNjByMEOzJO69VS5?	M3;5N\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ5NkC2OVQ3Lz5{N{[wOlU1PjxxYU6=
Sf9	M2THfGZ2dmO2aX;uJIF{e2G7			MVTJcohq[mm2aX;uJI9nKG[3bHygcIVv\3SqIILlZ49u[mmwYX70JIh2dWGwIFjERWM{N06FT2KyJIV5eHKnc4Pl[EBqdiCkYXP1cI93cXK3czDpcoZm[3SnZDDT[lkh[2WubIOgeZNqdmdiUljLT{1C[yCjczDzeYJ{fHKjdHWgZpkh\my3b4Lld4NmdmOnIHHuZYx6e2m\|LDDJR\|UxKD1iMD6wNFQ5PiEQvF2u	NH3OXIQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{N{[wOlU1Pid-Mke2NFY2PDZ:L3G+
HUT78	MYHGeY5kfGmxbjDhd5NigQ>?		NHruR2oyQCCqcoO=	M{\ifHBzdy2jcH;weI91cWNiYXP0bZZqfHliaX6gbJVu[W5iSGXUO\|gh[2WubIOgZYZ1\XJiMUigbJJ{KGK7IHPhd5Bie2VvR3zvJFMwPyCjc4PhfUwhTUN3MDC9JFAvODB4NTFOwG0v	M2XLZVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzNyMUKyNlI4Lz5\|MEGyNlIzPzxxYU6=
BL21 (DE3)	MX;GeY5kfGmxbjDhd5NigQ>?			NI\GcYJDcW6maX7nJIFn\mmwaYT5JJRwKGi3bXHuJGhqey22aHnvdoVld3irbj30ZYdo\WRiSFTBR\|gh\XiycnXzd4VlKGmwIFXzZ4hmemmlaHnhJINwdGliQlyyNUApTEV\|KTDj[YxteyCkeTDJWGMhdWW2aH;kMEBM\CB;IECuNFIzPyEQvF2u	MmC3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzB\|NEexOFgoRjNyM{S3NVQ5RC:jPh?=
BL21 (DE3)	NVfqT3YxTnWwY4Tpc44h[XO\|YYm=			MkHZRolv\GmwZzDh[oZqdmm2eTD0c{BU[2irc4Tvd49u[SCvYX7zc45qKEircz30ZYdo\WRiSFTBR\|gh\XiycnXzd4VlKGmwIFXzZ4hmemmlaHnhJINwdGliQlyyNUApTEV\|KTDj[YxteyCkeTDJWGMhdWW2aH;kMEBM\CB;IECuNFI5PCEQvF2u	NV;VcHJKRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxM{CzOFcyPDhpPkOwN\|Q4OTR6PD;hQi=>
BL21 (DE3)	MlTRSpVv[3Srb36gZZN{[Xl?			NYPkVXFNUW6qaXLpeIlwdiCxZjDoeY1idiCKaYOteIhqd3KnZH;4bY4ufGGpZ3XkJGhFSUN6IHX4dJJme3OnZDDpckBGe2OqZYLpZ4hq[SClb3zpJGJNOjFiKFTFN{kh[2WubIOgeZNqdmdiRnz1c5Ih\GViTInzJEhTMS2KRFHDPEBieyC\|dXLzeJJifGViYomg[ox2d3KxbXX0dolkKG2ndHjv[EwhUUN3MDC9JFAvODZ2NDFOwG0v	NFnJV249[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9\|MEO0O\|E1QCd-M{CzOFcyPDh:L3G+
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BL21 (DE3)	M{TaeGZ2dmO2aX;uJIF{e2G7			NH3pU\|hKdmirYnn0bY9vKG:oIHj1cYFvKEircz30bIlwemWmb4jpck11[WepZXSgTGRCSzhibVy2JI12fGGwdDDlfJBz\XO\|ZXSgbY4hTXOlaHXybYNpcWFiY3;sbUBDVDJzIDjESVMqKGOnbHzzJJV{cW6pIF\seY9zKGSnIFz5d{ApWilvSFTBR\|gh[XNic4Xid5Rz[XSnIHL5JIZtfW:{b33leJJq[yCvZYToc4QtKEmFNUCgQUAxNjB7MzFOwG0v	MYm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{ODN2N{G0PEc,OzB\|NEexOFg9N2F-
BL21 (DE3)	NUTmSZl{TnWwY4Tpc44h[XO\|YYm=			NVv0Z\|dFUW6qaXLpeIlwdiCxZjDoeY1idiCKaYOteIhqd3KnZH;4bY4ufGGpZ3XkJGhFSUN6IH3MNU9uVDZibYX0ZY51KGW6cILld5Nm\CCrbjDFd4Np\XKrY3jpZUBkd2yrIFLMNlEhMESHMzmgZ4VtdHNidYPpcochTmy3b4Kg[IUhVHm\|IDjSLU1JTEGFODDhd{B{fWK\|dILheIUh[nliZnz1c5JwdWW2cnnjJI1mfGixZDygTWM2OCB;IECuNFk1KM7:TT6=	NVf2bmZORGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxM{CzOFcyPDhpPkOwN\|Q4OTR6PD;hQi=>
BL21 (DE3)	MVHGeY5kfGmxbjDhd5NigQ>?			MUTJcohq[mm2aX;uJI9nKGi3bXHuJGhqey22aHnvdoVld3irbj30ZYdo\WRiSFTBR\|ghdUx4L1yxO\|lKKG23dHHueEBmgHC{ZYPz[YQhcW5iRYPjbIVzcWOqaXGgZ49tcSCETEKxJEhFTTNrIHPlcIx{KHW\|aX7nJGZtfW:{IHTlJGx6eyBqUjmtTGRCSzhiYYOgd5Vje3S{YYTlJIJ6KG[udX;yc41mfHKrYzDt[ZRpd2RuIFnDOVAhRSByLkG2PUDPxE1w	NHLGTYs9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9\|MEO0O\|E1QCd-M{CzOFcyPDh:L3G+
BL21 (DE3)	NGTqZmtHfW6ldHnvckBie3OjeR?=			NX;lN3p6UW6qaXLpeIlwdiCxZjDoeY1idiCKaYOteIhqd3KnZH;4bY4ufGGpZ3XkJGhFSUN6IH3MNU9uVDZxTEG3PWkhdXW2YX70JIV5eHKnc4Pl[EBqdiCHc3Po[ZJq[2irYTDjc4xqKEKOMkGgLGRGOyliY3XscJMhfXOrbnegSox2d3JiZHWgUJl{KCiUKT3ISGFEQCCjczDzeYJ{fHKjdHWgZpkh\my3b4LvcYV1emmlIH3leIhw\CxiSVO1NEA:KDBwMkG3JO69VS5?	M4rM[lxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzNyM{S3NVQ5Lz5\|MEO0O\|E1QDxxYU6=
BL21 (DE3)	MXHGeY5kfGmxbjDhd5NigQ>?			M3v4bWlvcGmkaYTpc44hd2ZiU3PobZN1d3OxbXGgcYFve2:waTDIbZMufGGpZ3XkJGhFSUN6IHX4dJJme3OnZDDpckBGe2OqZYLpZ4hq[SClb3zpJGJNOjFiKFTFN{kh[2WubIOgeZNqdmdiRnz1c5Ih\GViTInzJEhTMS2KRFHDPEBieyC\|dXLzeJJifGViYomg[ox2d3KxbXX0dolkKG2ndHjv[EwhUUN3MDC9JFAvOzB\|NDFOwG0v	MUi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{ODN2N{G0PEc,OzB\|NEexOFg9N2F-
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U-2 OS	M1vSN5FJXFNiYYPzZZk>			MWPxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhXS1{IF;TJINmdGy\|	NXf0bmtoRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
A673	NXj0SVhkeUiWUzDhd5NigQ>?			NVfPNJloeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IFG2O\|Mh[2WubIO=	M2XjO\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
DAOY	NVPKfHhteUiWUzDhd5NigQ>?			MUDxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhTEGRWTDj[Yxtew>?	M3nFPVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
Saos-2	NHPveXNyUFSVIHHzd4F6			NHi3e5ByUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiU3Hvd{0zKGOnbHzz	MX28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
BT-37	MXnxTHRUKGG\|c3H5			MofndWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKEKWLUO3JINmdGy\|	MVS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
RD	MVLxTHRUKGG\|c3H5			MXLxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhWkRiY3XscJM>	M{\vfFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
SK-N-SH	MUHxTHRUKGG\|c3H5			NET4NXFyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiU1utUk1UUCClZXzsdy=>	MnXaQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
BT-12	M{jiOZFJXFNiYYPzZZk>			M3\uSZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCEVD2xNkBk\Wyucx?=	M{jvU\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
MG 63 (6-TG R)	MnzKdWhVWyCjc4PhfS=>			MW\xTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhVUdiNkOgLFYuXEdiUjmgZ4VtdHN?	MYS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
NB1643	NXfZZ5cyeUiWUzDhd5NigQ>?			MnThdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKE6EMU[0N{Bk\Wyucx?=	M3rl[VxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
OHS-50	NVLzcXlpeUiWUzDhd5NigQ>?			MnzBdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKE:KUz21NEBk\Wyucx?=	M4nTOVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
BT-12	MlPTdWhVWyCjc4PhfS=>			NVfTN25neUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiQ3;u[olzdWG2b4L5JJNkemWnbjDmc5IhSlRvMUKgZ4VtdHN?	M1\DNlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
DAOY	NUiycmlSeUiWUzDhd5NigQ>?			NIj4PWFyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBFSU:\IHPlcIx{	NGm1SWk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
fibroblast cells	NWHqZ5k{eUiWUzDhd5NigQ>?			MWjxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5Ih[2:wdILvcEBJcCC5aXzkJJR6eGViZnnido9jdGG\|dDDj[Yxtew>?	MXW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
SK-N-SH	NF;xW\|NyUFSVIHHzd4F6			MVPxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBEd26oaYLtZZRwenlic3Py[YVvKG[xcjDTT{1PNVOKIHPlcIx{	Mly1QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
Rh41	NIjZUFJyUFSVIHHzd4F6			MoC2dWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKFKqNEGgZ4VtdHN?	MV:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
A673	M{jPTZFJXFNiYYPzZZk>			NYDlT4FSeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiQ3;u[olzdWG2b4L5JJNkemWnbjDmc5IhSTZ5MzDj[Yxteyl?	MXy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
Rh30	M37WfpFJXFNiYYPzZZk>			NXm0[VRqeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IGLoN\|Ah[2WubIO=	NYCz[nQxRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
MG 63 (6-TG R)	MWPxTHRUKGG\|c3H5			MXnxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBEd26oaYLtZZRwenlic3Py[YVvKG[xcjDNS{A3OyBqNj3US{BTMSClZXzsdy=>	MWG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
fibroblast cells	M1PlOZFJXFNiYYPzZZk>			Mke4dWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohS2:wZnnycYF1d3K7IIPjdoVmdiCob4KgZ49vfHKxbDDIbEB4cWymIIT5dIUh\mmkcn;icIF{fCClZXzsdy=>	MX:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
Rh30	NULaV4NIeUiWUzDhd5NigQ>?			M17RR5FJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJHJpOzBiY3XscJM>	MYK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
U-2 OS	NUDvVlBueUiWUzDhd5NigQ>?			MVjxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBEd26oaYLtZZRwenlic3Py[YVvKG[xcjDVMVIhV1NiY3XscJM>	MXy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
OHS-50	NXLwdFc3eUiWUzDhd5NigQ>?			MXHxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBEd26oaYLtZZRwenlic3Py[YVvKG[xcjDPTHMuPTBiY3XscJM>	M3PRdFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
SK-N-SH	M1XBd5FJXFNiYYPzZZk>			NWTKT3dTeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiT4L0bI9od26jbDCzSEB3cWGkaXzpeJkhe2O{ZXXuJIZweiCVSz3OMXNJKGOnbHzz	MnzhQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
Rh41	NEDkclRyUFSVIHHzd4F6			M{iyTZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJHJpPDFiY3XscJM>	NFmzUZI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
RD	Mke4dWhVWyCjc4PhfS=>			MoizdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohS2:wZnnycYF1d3K7IIPjdoVmdiCob4KgVmQh[2WubIO=	M4q2XFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
Daoy	MmTKdWhVWyCjc4PhfS=>			MXrxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBQenSqb3fvcoFtKDOGII\pZYJqdGm2eTDzZ5Jm\W5iZn;yJGRid3liY3XscJM>	NFjqVYM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
TC32	NYPoZ3RLeUiWUzDhd5NigQ>?			M4fJbZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KE:{dHjv[49v[WxiM1Sgeoli[mmuaYT5JJNkemWnbjDmc5IhXEN\|MjDj[Yxtew>?	MkDlQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
MG 63 (6-TG R)	M2jW[5FJXFNiYYPzZZk>			NGezfodyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCRcoToc4dwdmGuIEPEJJZq[WKrbHn0fUB{[3KnZX6g[o9zKE2JIE[zJEg3NVSJIGKpJINmdGy\|	NID1V4o9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
SJ-GBM2	Mm\idWhVWyCjc4PhfS=>			M2WyZZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCVSj3HRm0zKGOnbHzz	Mnv0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
SK-N-MC	NFH3d\|ZyUFSVIHHzd4F6			NH;Je3VyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiU1utUk1OSyClZXzsdy=>	MVe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
NB-EBc1	NF\RVXdyUFSVIHHzd4F6			MVjxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhVkJvRVLjNUBk\Wyucx?=	M2DudlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
LAN-5	NGi0XVJyUFSVIHHzd4F6			NGnB[3hyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiTFHOMVUh[2WubIO=	M{i3ZlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
Rh18	MV\xTHRUKGG\|c3H5			Ml3ydWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKFKqMUigZ4VtdHN?	NXnoUXhRRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
NB1643	MYnxTHRUKGG\|c3H5			M4rkbZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJG5DOTZ2MzDj[Yxtew>?	NVH3c5JjRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
SJ-GBM2	Ml36dWhVWyCjc4PhfS=>			NVzEeG1CeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiQ3;u[olzdWG2b4L5JJNkemWnbjDmc5IhW0pvR1LNNkBk\Wyucx?=	MkCxQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
Rh18	NVjaV4k2eUiWUzDhd5NigQ>?			Mn\kdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohS2:wZnnycYF1d3K7IIPjdoVmdiCob4KgVogyQCClZXzsdy=>	MYm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
Saos-2	NGXCbZZyUFSVIHHzd4F6			NFnUbIVyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBU[W:\|LUKgZ4VtdHN?	M3T0fVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
SJ-GBM2	NHHhU2dyUFSVIHHzd4F6			NX2w[5l7eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiT4L0bI9od26jbDCzSEB3cWGkaXzpeJkhe2O{ZXXuJIZweiCVSj3HRm0zKGOnbHzz	NHvuNJE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
RD	MljVdWhVWyCjc4PhfS=>			MVTxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBQenSqb3fvcoFtKDOGII\pZYJqdGm2eTDzZ5Jm\W5iZn;yJHJFKGOnbHzz	NITtZ5g9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+

... Click to View More Cell Line Experimental Data

Assay

Methods	Test Index	PMID
Western blot	HDAC1 / HDAC2 / HDAC4; PubMed: 30443188 Int J Biol Sci The effects of quisinostat on the expressions of HDACs in HCC cells. The expression levels of HDAC1, HDAC2 and HDAC4 were suppressed in both HCCLM3 and SMMC-7721 cell lines. Images were photographed with confocal microscope under ×200 magnification. Scale bar, 100 μm. Data were shown as mean ± SD. n = 3; * P < 0.05, P < 0.01 and * P < 0.001 compared with DMSO group. p21 / CDK2 / CDK4 / CDK6 / Cyclin D1 / Cyclin E1 / Cyclin A2; PubMed: 30443188 Int J Biol Sci Western blot analysis of p21, cdk2, cdk4, cdk6, cyclinD1, cyclinE1 and cyclinA2 proteins after quisinostat treatment. Caspase-3/ Cleaved caspase-3 / caspase-9 / Cleaved caspase-9 / PARP / Cleaved PARP / Bcl-xl / Bcl2 / Bax / Survivin; PubMed: 30443188 Int J Biol Sci Western blot analysis of Caspase-3, cleaved-Caspase-3, Caspase-9, cleaved-Caspase-9, PARP, cleaved-PARP, Bcl-xl, Bcl2, Bax and survivin protein were carried out after quisinostat treatment. PI3K-p110 / PI3K-p85 / p-AKT / JNK / p-JNK / p-c-Jun ; PubMed: 30443188 Int J Biol Sci HCCLM3 and SMMC-7721 cells were treated with quisinostat (12.5, 25.0 and 50.0nM) for 48 h. Western blot analysis was used to evaluate expressions of PI3K-p110, PI3K-p85, phosphorylation of AKT473, JNK, phosphorylation of JNK and c-Jun.	30443188
Growth inhibition assay	Cell viability; PubMed: 30443188 Int J Biol Sci Quisinostat inhibited cell proliferation in HCCLM3, Sk-hep-1, Hep-3B, Huh7 and SMMC-7721 cells as a concentration-dependent manner verified by CCK8 assay.	30443188

In vivo

In an HDAC1-responsive A2780 ovarian tumor screening model, JNJ-26481585 dosing at its maximal tolerated dose (10 mg/kg i.p. and 40 mg/kg p.o.) for 3 days leads to an HDAC1-regulated fluorescence , which predicts tumor growth inhibition. Furthermore, JNJ-26481585 also shows more potent inhibitory effects on the growth of C170HM2 colorectal liver metastases than 5-fluorouracil/Leucovorin. ^[1]

Protocol

Kinase Assay:^[1]	- Collapse HDAC activity assays : In all cases, full-length HDAC proteins are expressed using baculovirus-infected Sf9 cells. In addition, HDAC3 is coexpressed as a complex with human NCOR2. For assessing activity of HDAC1-containing cellular complexes, immunoprecipitated HDAC1 complexes are incubated with an [³H]acetyl- labeled fragment of histone H4 peptide [biotin-(6-aminohexanoic)Gly-Ala-(acetyl[3H])Lys-Arg-His-Arg-Lys-Val-NH2] in a total volume of 50μL enzyme assay buffer (25mM HEPES (pH 7.4), 1 M sucrose, 0.1 mg/mL BSA and 0.01% (v/v) Triton X-100). Incubation is performed for 45 minutes at 37 °C (immunoprecipitates) or 30 min at room temperature. Before addition of substrate, HDAC inhibitors are added at increasing concentrations and preincubated for 10 minutes at room temperature. After incubation, the reaction is quenched with 35μL stop buffer (1 M HCl and 0.4 M acetic acid). Released [³H]acetic acid is extracted with 800μL ethyl acetate and quantified by scintillation counting. Equal amounts of HDAC1 are immunoprecipitated as indicated by Western blot analysis. HDAC1 activity results are presented as mean ± SD of three independent experiments on a single lysate.
Cell Research:Cell proliferation assays	- Collapse Cell lines: NCL-H2106, Colo699 and LNCAP cells Concentrations: 0-300 nM Incubation Time: 24 hours Method: All cell lines are obtained from American Type Culture Collection and cultured according to instructions. The effect of HDAC inhibitors on cell proliferation is measured using an MTT. Proliferation of non–small cell lung carcinoma (NSCLC) cell lines is assessed using an Alamar Blue–based assay. For proliferation of hematologic cell lines, cells are incubated for 72 hours and the cytotoxic activity is evaluated by MTS assay. Data are presented as mean IC50 or IC40 ± SD of at least three independent experiments. (Only for Reference)
Animal Research:^[1]	- Collapse Animal Models: HCT116 human colon carcinoma cells are injected s.c. into the inguinal region of athymic male NMRI nu/nu mice, C170HM2 cell suspensions are injected into the peritoneal cavity of male MFI nude mice. Dosages: ≤10 mg/kg Administration: Administered via both p.o. and i.p. (Only for Reference)

References

Solubility (25°C)

In vitro	DMSO	79 mg/mL (169.02 mM)
	Water	Insoluble
	Ethanol	Insoluble
In vivo	Add solvents to the product individually and in order(Data is from Selleck tests instead of citations): 2% DMSO+30% PEG 300+ddH2O For best results, use promptly after mixing.	5mg/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	467.39
Formula	C₂₁H₂₈Cl₂N₆O₂
CAS No.	875320-31-3
Storage	3 years-20°C powder 2 years-80°C in solvent
Synonyms	N/A
Smiles	CN1C=C(C2=CC=CC=C21)CNCC3CCN(CC3)C4=NC=C(C=N4)C(=O)NO.Cl.Cl

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Method for preparing DMSO master liquid: ： mg drug pre-dissolved in μL DMSO (Master liquid concentration mg/mL， Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation：Take μL DMSO master liquid, next addμL PEG300， mix and clarify, next addμL Tween 80，mix and clarify, next add μL ddH₂O，mix and clarify.

Note：1.Please make sure the liquid is clear before adding the next solvent.
2.Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.

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The Serial Dilution Calculator Equation

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Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

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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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Frequently Asked Questions

Question 1:
I was thinking of resuspending the powder in 10% hydroxy-propyl-β-cyclodextrin, 25mg/ml mannitol, in sterile water (final pH 8.7). Is this a good vehicle to use? What is the solubility of this chemical in such a vehicle?
Answer:
This vehicle can be used for in vivo studies. The following papers also used this vehicle: 1. http://www.nature.com/leu/journal/v23/n10/full/leu2009121a.html; 2. http://cancerres.aacrjournals.org/content/69/13/5307.long (The solvent contains 10% hydroxypropyl-β-cyclodextrin, 0.8% HCl (0.1 N), 0.9 % NaOH (0.1 N), 3.4% mannitol and pyrogen-free water). The solubility is 2mg/ml.

HDAC Signaling Pathway Map

HDAC Inhibitors with Unique Features

Selective HDAC Inhibitors

RGFP966 : HDAC3-selective, IC50=80 nM.
Selective HDAC Inhibitors

Rocilinostat (ACY-1215) : HDAC5-selective, IC50=5 nM.
FDA-approved HDAC Inhibitor

Vorinostat (SAHA, MK0683) : Approved by FDA against cutaneous T cell lymphoma.
Newest HDAC Inhibitor

RG2833 (RGFP109) ^New : Brain-penetrant HDAC inhibitor with IC50 of 60 nM and 50 nM for HDAC1 and HDAC3, respectively.
Classic HDAC Inhibitor

Panobinostat (LBH589) : Novel broad-spectrum HDAC inhibitor with IC50 of 5 nM.

Related HDAC Products

LMK-235 ^New

LMK-235 is a selective inhibitor of HDAC4 and HDAC5 with IC50 of 11.9 nM and 4.2 nM, respectively.
CAY10603 ^New

CAY10603 (BML-281) is a potent and selective HDAC6 inhibitor with IC50 of 2 pM, >200-fold selectivity over other HDACs.
Domatinostat (4SC-202) ^New

Domatinostat (4SC-202) is a selective class I HDAC inhibitor with IC50 of 1.20 μM, 1.12 μM, and 0.57 μM for HDAC1, HDAC2, and HDAC3, respectively. Also displays inhibitory activity against Lysine specific demethylase 1 (LSD1). Phase 1.
Panobinostat (LBH589)

Panobinostat (LBH589, NVP-LBH589) is a novel broad-spectrum HDAC inhibitor with IC50 of 5 nM in a cell-free assay. Panobinostat (LBH589) induces autophagy and apoptosis. Panobinostat effectively disrupts HIV latency in vivo. Phase 3.
Vorinostat (SAHA)

Vorinostat (suberoylanilide hydroxamic acid, SAHA, MK0683) is an HDAC inhibitor with IC50 of ~10 nM in a cell-free assay. Vorinostat abrogates productive HPV-18 DNA amplification.
Entinostat (MS-275)

Entinostat (MS-275, SNDX-275) strongly inhibits HDAC1 and HDAC3 with IC50 of 0.51 μM and 1.7 μM in cell-free assays, compared with HDACs 4, 6, 8, and 10. Entinostat induces autophagy and apoptosis. Phase 3.
Trichostatin A (TSA)

Trichostatin A (TSA) is an HDAC inhibitor with IC50 of ~1.8 nM in cell-free assays.
Romidepsin (FK228, Depsipeptide)

Romidepsin (FK228, Depsipeptide, FR 901228, NSC 630176) is a potent HDAC1 and HDAC2 inhibitor with IC50 of 36 nM and 47 nM in cell-free assays, respectively. Romidepsin (FK228/depsipeptide) controls growth and induces apoptosis in neuroblastoma tumor cells.

Features:More effective than other classical HDAC inhibitors such as TSA, TPX, and butyrate.
RGFP966

RGFP966 is an HDAC3 inhibitor with IC50 of 0.08 μM in cell-free assay, exhibits > 200-fold selectivity over other HDAC.
Tubastatin A

Tubastatin A is a potent and selective HDAC6 inhibitor with IC50 of 15 nM in a cell-free assay. It is selective against all the other isozymes (1000-fold) except HDAC8 (57-fold). Tubastatin A promotes autophagy and increases apoptosis.

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Quisinostat (JNJ-26481585) 2HCl