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Mocetinostat (MGCD0103)

Name: Mocetinostat (MGCD0103)
Brand: Selleck Chemicals
SKU: S1122
Rating: 5 (93 reviews)

Catalog No.S1122 Synonyms: MG0103

For research use only.

Mocetinostat (MGCD0103, MG0103) is a potent HDAC inhibitor with most potency for HDAC1 with IC50 of 0.15 μM in a cell-free assay, 2- to 10- fold selectivity against HDAC2, 3, and 11, and no activity to HDAC4, 5, 6, 7, and 8. Mocetinostat (MGCD0103) induces apoptosis and autophagy. Phase 2.

Mocetinostat (MGCD0103) Chemical Structure

CAS No. 726169-73-9

Selleck's Mocetinostat (MGCD0103) has been cited by 93 publications

Purity & Quality Control

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HDAC Signaling Pathway Map

Biological Activity

Description

Targets

HDAC1 ^[1] (Cell-free assay)	HDAC2 ^[1] (Cell-free assay)	HDAC11 ^[1] (Cell-free assay)	HDAC3 ^[1] (Cell-free assay)
0.15 μM	0.29 μM	0.59 μM	1.66 μM

In vitro

MGCD0103 inhibits only a subset of the nine human recombinant HDACs, including HDAC1, HDAC2, HDAC3, and HDAC11 at nanomolar or low micromolar concentrations, in a dose-dependent manner. MGCD0103 reveals most potent inhibitory activity against human HDAC1 and HDAC2 enzymes in vitro, and it does not inhibit class II HDACs. The exocyclic amino group in MGCD0103 is necessary for enzyme inhibitory activity because HDAC-inhibitory activity against HDAC1 and HDAC2 is completely abolished with the desamino analogue. The inhibitory activity of MGCD0103 reaches the maximum plateau at 6 μM, and the maximal inhibitable enzyme pool affected by MGCD0103 is 75% of the total enzyme activity in HCT116 cells whereas NVP-LAQ824 inhibits almost 100% of that in these cells. In A549 cells, MGCD0103 also exhibits dose-dependent inhibition of HDAC activity in whole cells. ^[1]

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Formulation	Activity Description	PMID

PBMC	MVLBdI9xfG:\|aYOgRZN{[Xl?	MoruNE42NzJxMzFOwG0>	M1fwNlI1NzR6IHi=		NX;hWoRncW6mdXPld{BieG:ydH;zbZMh\G:\|ZTDhcoQhfGmvZTDk[ZBmdmSnboTsfS=>	NUfC[FRGRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkC0NFY6PDdpPkKwOFA3QTR5PD;hQi=>
HeLa	NXLQZpFtTnWwY4Tpc44hSXO\|YYm=	MWOxNEDPxE4EoB?=	MlrDO{Bp	NFv0U2pFVVOR	Ml;V[Il{enWydIOgco9zdWGuIIPwbY5ldGViY3jlZ4txd2mwdDDmeY5kfGmxbh?=	NITNUGI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MEWzPFg1OCd-MkC1N\|g5PDB:L3G+
HeLa	NHr2NW1HfW6ldHnvckBCe3OjeR?=	MV:xNEDPxE4EoB?=	M3HVO\|YwOTJxMkSgbC=>	MonKSG1UVw>?	MlK3bY5lfWOnczDtbZRwfGmlIHHjZ5VufWyjdHnvckBidmRiZHXsZZlm\CCyMkGg[ZhxemW\|c3nvci=>	M2fWZ\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJyNUO4PFQxLz5{MEWzPFg1ODxxYU6=
HeLa	MYnGeY5kfGmxbjDBd5NigQ>?	MoXaNE4{NTFyIN88US=>	M{H2bVghcA>?	NEXEV3dFVVOR	M2fZdIlv[3KnYYPld{Bk[XOyYYPlJFMh[W6mIEegZYN1cX[jdHnvckBld3OnIHTldIVv\GWwdHz5	NUXrWplGRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkC1N\|g5PDBpPkKwOVM5QDRyPD;hQi=>
HeLa	NGDoXlBHfW6ldHnvckBCe3OjeR?=	NW\mWYNWOC5\|LUGwJO69VQ>?	NXTzNo9NQCCq	NUPiXYhoTE2VTx?=	NFzRfWRqdmO{ZXHz[ZMh[WOndInsZZRm\CCKMzDLPUApUDONOVHjLUBifCBzMDFOwG0>	NV;TRmY3RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkC1N\|g5PDBpPkKwOVM5QDRyPD;hQi=>
DMS114	M3zXeGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7				MX\JR\|UxRTZ2MDDuUS=>	M4SyVFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJyNkiyOlQ{Lz5{ME[4NlY1OzxxYU6=
H82	MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?				NYTDfYQ3UUN3ME2yOVAhdk1?	M1XnTVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJyNkiyOlQ{Lz5{ME[4NlY1OzxxYU6=
H146	MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?				NYLkU3BVUUN3ME2zOUBvVQ>?	MUO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zODZ6Mk[0N{c,OjB4OEK2OFM9N2F-
H526	M3fB[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7				M4XSZmlEPTB;NEiwJI5O	NXnsO4x3RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkC2PFI3PDNpPkKwOlgzPjR\|PD;hQi=>
KM-H2	NVrzdWVSTnWwY4Tpc44hSXO\|YYm=	M2[5VlHDqM7:TR?=	MU[wMlI2NTR6IHi=	NYi5PXU5TE2VTx?=	NX\5ephs[WO2aY\heIV{KE6ILXvC	M{frO\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJyOEiwNVA4Lz5{MEi4NFExPzxxYU6=
L428	MWrGeY5kfGmxbjDBd5NigQ>?	NYjEWJQ4OcLizszN	Mly4NE4zPS12ODDo	NF64dVdFVVOR	M{LhS4FkfGm4YYTld{BPTi2tQh?=	Mmn0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjB6OECxNFcoRjJyOEiwNVA4RC:jPh?=
HD-LM2	NH7VVWdHfW6ldHnvckBCe3OjeR?=	MlPrNeKh\|ryP	M3rWTFAvOjVvNEigbC=>	NX62cZRLTE2VTx?=	M1riSIFkfGm4YYTld{BPTi2tQh?=	M3;SU\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJyOEiwNVA4Lz5{MEi4NFExPzxxYU6=
KM-H2	NVntPWl{TnWwY4Tpc44hSXO\|YYm=	NEHqNWQxNjVxMTFOwG0>	NV3XRpVWOjRxNEigbC=>	NWTocpc3TE2VTx?=	MV\1dJJm\3WuYYTld{BVVkZvzsGg[I9{\SCjbnSgeIlu\SCmZYDlcoRmdnSueR?=	Ml;QQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjB6OECxNFcoRjJyOEiwNVA4RC:jPh?=
L428	MWLGeY5kfGmxbjDBd5NigQ>?	NEe3OXkxNjVxMTFOwG0>	M2e1U\|I1NzR6IHi=	NELDfFlFVVOR	M3jNNpVxemWpdXzheIV{KFSQRj5OtUBld3OnIHHu[EB1cW2nIHTldIVv\GWwdHz5	NVjkOYFrRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkC4PFAyODdpPkKwPFgxOTB5PD;hQi=>
HD-LM2	MoniSpVv[3Srb36gRZN{[Xl?	NV;0c5REOC53L{Gg{txO	NXnWd2xiOjRxNEigbC=>	NGTNdJJFVVOR	M3Xld5VxemWpdXzheIV{KFSQRj5OtUBld3OnIHHu[EB1cW2nIHTldIVv\GWwdHz5	NIC4cGM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MEi4NFExPyd-MkC4PFAyODd:L3G+
KM-H2	NFj3[m1HfW6ldHnvckBCe3OjeR?=	NIXTTIUyyqEQvF2=	MVWyOE81QCCq	MVzEUXNQ	NYi4O4sx\G:5boLl[5Vt[XSnczDYTWFRNCCjY4TpeoF1\WRiY3HzdIF{\XNiOTDhcoQhOw>?	MnroQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjB6OECxNFcoRjJyOEiwNVA4RC:jPh?=
L428	MorqSpVv[3Srb36gRZN{[Xl?	M{foe\|HDqM7:TR?=	MnjZNlQwPDhiaB?=	MmnnSG1UVw>?	NVrGbnNb\G:5boLl[5Vt[XSnczDYTWFRNCCjY4TpeoF1\WRiY3HzdIF{\XNiOTDhcoQhOw>?	NUL1OXpHRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkC4PFAyODdpPkKwPFgxOTB5PD;hQi=>
HD-LM2	M4HaWWZ2dmO2aX;uJGF{e2G7	Mlu1NeKh\|ryP	M{ThTlI1NzR6IHi=	M1uybWROW09?	NHLITnRld3ewcnXneYxifGW\|IGjJRXAtKGGldHn2ZZRm\CClYYPwZZNmeyB7IHHu[EA{	NYHT[o91RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkC4PFAyODdpPkKwPFgxOTB5PD;hQi=>
KM-H2	MUHBdI9xfG:\|aYOgRZN{[Xl?	NFHOTm0xNjFxMD61M\|Eh\|ryP	MoC2OFghcA>?	NHW4bFNFVVOR	M2Hjbolv\HWlZYOgZZBweHSxc3nzJIRwe2ViZHXw[Y5l\W62bIm=	NVXDbWZnRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkC4PFAyODdpPkKwPFgxOTB5PD;hQi=>
L428	MlHoRZBweHSxc3nzJGF{e2G7	MmjnNE4yNzBwNT:xJO69VQ>?	Mkf3OFghcA>?	M2XZdGROW09?	NYrxbXBkcW6mdXPld{BieG:ydH;zbZMh\G:\|ZTDk[ZBmdmSnboTsfS=>	MVi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zODh6MEGwO{c,OjB6OECxNFc9N2F-
HD-LM2	NIr3[45CeG:ydH;zbZMhSXO\|YYm=	NW\GSmFvOC5zL{CuOU8yKM7:TR?=	MnrGOFghcA>?	MWrEUXNQ	MWHpcoR2[2W\|IHHwc5B1d3OrczDkc5NmKGSncHXu[IVvfGy7	NYjDdoJNRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkC4PFAyODdpPkKwPFgxOTB5PD;hQi=>
KM-H2	MVPGeY5kfGmxbjDBd5NigQ>?	NGSyN28xNjFvMjFOwG0>	NV7JOZI3OjRiaNMg	NIXBNVFFVVOR	MoPhd4hwf3NiYXPleJlt[XSrb36gc4YhcGm\|dH;u[UA{KGGwZDD1dJJm\3WuYYTpc44hd2ZidHjlJINmdGxiY4njcIUhemWpdXzheI9zgSCycn;0[YlvKHB{MR?=	NUDGfVc1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkC4PFAyODdpPkKwPFgxOTB5PD;hQi=>
L428	MoKySpVv[3Srb36gRZN{[Xl?	MWCwMlEuOiEQvF2=	NU\CSVZlOjRiaNMg	M2\pPWROW09?	MV3zbI94eyCjY3X0fYxifGmxbjDv[kBpcXO2b37lJFMh[W6mIIXwdoVofWyjdHnvckBw\iC2aHWgZ4VtdCCleXPs[UBz\We3bHH0c5J6KHC{b4TlbY4heDJz	MlfCQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjB6OECxNFcoRjJyOEiwNVA4RC:jPh?=
HD-LM2	M4XnRmZ2dmO2aX;uJGF{e2G7	M{\rRlAvOS1{IN88US=>	NHTpOlgzPCCqwrC=	NGi3W2hFVVOR	NICxeod{cG:5czDhZ4V1gWyjdHnvckBw\iCqaYP0c45mKDNiYX7kJJVxemWpdXzheIlwdiCxZjD0bIUh[2WubDDjfYNt\SC{ZXf1cIF1d3K7IIDyc5RmcW5icEKx	M4q5WFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJyOEiwNVA4Lz5{MEi4NFExPzxxYU6=
KM-H2	NELSN49Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?=		NXTsUFkxPzMEoHi=	NVrG[WIzTE2VTx?=	MWLJR\|UxRTJwOE[g{txO	NIrwUlg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MEi4NFExPyd-MkC4PFAyODd:L3G+
L428	M4LFVGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7		NVPNTVU4PzMEoHi=	NUPtVY81TE2VTx?=	NVnZdHFKUUN3ME2xMlk3KM7:TR?=	MoPuQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjB6OECxNFcoRjJyOEiwNVA4RC:jPh?=
HD-LM2	MkHwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?		NIn0WHA4OsLiaB?=	NUPFNW5lTE2VTx?=	MUTJR\|UxRTFwOEig{txO	NEXhPZg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MEi4NFExPyd-MkC4PFAyODd:L3G+
LP1	M2mwfWZ2dmO2aX;uJGF{e2G7	MWOxxsDPxE1?	M1e3UVI1KGh?		NELXZZhmdmijbnPld{A2NUGFLXnu[JVk\WRiTVHHSU1COyCpZX7lJIV5eHKnc4Ppc44>	MlzSQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjFzN{G4NlEoRjJzMUexPFIyRC:jPh?=
ANBL6	MlPCSpVv[3Srb36gRZN{[Xl?	MUexxsDPxE1?	M2XNXVI1KGh?		NYTVbVRS\W6qYX7j[ZMhPS2DQz3pcoR2[2WmIF3BS2UuSTNiZ3Xu[UBmgHC{ZYPzbY9v	M4\HOlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzMUexPFIyLz5{MUG3NVgzOTxxYU6=
HMEC	MlflS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?				M{fPemlEPTB;MUmg{txO	NET4UXk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUOxO\|Q2PSd-MkGzNVc1PTV:L3G+
SW620	Mnq4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?				MULJR\|UxRTFizszN	MXi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTNzN{S1OUc,OjF\|MUe0OVU9N2F-
SW48	NWXKTWM4T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=				M2LIXmlEPTB;MD64JO69VQ>?	MXK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTNzN{S1OUc,OjF\|MUe0OVU9N2F-
HT-29	Mn\PS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?				M2PWTmlEPTB;MD63JO69VQ>?	Mnq2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF\|MUe0OVUoRjJzM{G3OFU2RC:jPh?=
HCT15	MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?				NYTrd\|ZkUUN3ME2wMlch\|ryP	NIC5VWs9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUOxO\|Q2PSd-MkGzNVc1PTV:L3G+
PAXF 1657L†	MkCwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?				NVj3e4pzTUN3ME2wMlMh\|ryP	M33DN\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzM{e1Olc6Lz5{MUO3OVY4QTxxYU6=
PAXF 546L†	MnW2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?				M1PiS2VEPTB;MT61JO69VQ>?	NFjNfI49[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUO3OVY4QSd-MkGzO\|U3Pzl:L3G+
Panc-1	MmfjS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?				M3W5e2VEPTB;MT64JO69VQ>?	MWW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTN5NU[3PUc,OjF\|N{W2O\|k9N2F-
MiaPaca-2	MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?				M1ezNGVEPTB;MD62JO69VQ>?	MVe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTN5NU[3PUc,OjF\|N{W2O\|k9N2F-
AsPC-1	MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?				NV7POYlrTUN3ME2zMlkh\|ryP	MWm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTN5NU[3PUc,OjF\|N{W2O\|k9N2F-
BxPC-3	MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?				NETMeoNGSzVyPUGuNUDPxE1?	MYW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTN5NU[3PUc,OjF\|N{W2O\|k9N2F-
MMCs	NFXmR3RHfW6ldHnvckBCe3OjeR?=	M1PoTFHDqM7:TR?=	MWS2MVI1KGh?		NWDSfHpT\G:\|ZT3k[ZBmdmSnboTsfUBqdmirYnn0d{B1cGVidILpcYV1cHmuYYTpc44hdGW4ZXygc4YhUDNvS{mgLGg{NUt7bXWzLS=>	MX:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDR3MUO3PEc,OjR2NUGzO\|g9N2F-
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Jurkat	NV21OWk6TnWwY4Tpc44h[XO\|YYm=	MmniNUB1dyBzMDD1US=>	NVLRUoZwOjRiaILz		NFTQbGZKdmirYnn0bY9vKG:oIFjERWMhcW5iaIXtZY4hUnW{a3H0JINmdGy\|IHHzd4V{e2WmIHHzJIlv[3KnYYPlJIlvKEh\|S{nBZ{Bt\X[nbDDheEAyKHSxIEGwJJVOKGGodHXyJFI1KGi{czDifUBY\XO2ZYLuJIJtd3RiYX7hcJl{cXN?	NXvSNnRjRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO4Nlk1QDNpPkKzPFI6PDh\|PD;hQi=>
High5	NIXSRlhHfW6ldHnvckBie3OjeR?=		MoDXN{B1dyB{NDDodpM>		Mne5TY5pcWKrdHnvckBw\iCqdX3hckBz\WOxbXLpcoFvfCCKRFHDNUBmgHC{ZYPz[YQhcW5iYnHjeYxwfmm{dYOgbY5n\WO2ZXSgbY5{\WO2IHjp[4g2KGOnbHzzJJV{cW6pIFHjMWx6ey2WeYKtUJl{KCincIPpcI9vNWGlZYT5cEkuSU2FIHHzJJN2[nO2cnH0[UBi\nSncjCzJJRwKDJ2IHjyd{BjgSCobIXvdoV{[2WwY3WgZZN{[XluIFnDOVA:OC57Nd88US=>	NGXi[VM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEC5OVAyQCd-MkSwPVUxOTh:L3G+
HCT116	NX[5XFltSW62aYDyc4xq\mW{YYTpeoUh[XO\|YYm=		M1;0fFczKGi{cx?=		Mmn4RY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6\|dDDoeY1idiCKQ2SxNVYh[2WubIOgZZN{\XO\|ZXSgZZMh[2WubDD2bYFjcWyrdImgZYZ1\XJiN{KgbJJ{KGK7IF3UWEBie3OjeTygTWM2OD1zLkW3{txO	MVS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDB7NUCxPEc,OjRyOUWwNVg9N2F-
A549	NWnQZYNHSW62aYDyc4xq\mW{YYTpeoUh[XO\|YYm=		NHq1VGE4OiCqcoO=		NWH3flNGSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDBOVQ6KGOnbHzzJIF{e2W\|c3XkJIF{KGOnbHygeoli[mmuaYT5JIFnfGW{IEeyJIhzeyCkeTDNWHQh[XO\|YYmsJGlEPTB;MT62Oe69VQ>?	NHXveok9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEC5OVAyQCd-MkSwPVUxOTh:L3G+
High5	NUHv[HNXTnWwY4Tpc44h[XO\|YYm=		M1zo[VMhfG9iMkSgbJJ{		MmXlTY5pcWKrdHnvckBw\iCqdX3hckBz\WOxbXLpcoFvfCCKRFHDN{BmgHC{ZYPz[YQhcW5iYnHjeYxwfmm{dYOgbY5n\WO2ZXSgbY5{\WO2IHjp[4g2KGOnbHzzJJV{cW6pIFHjMWx6ey2WeYKtUJl{KCincIPpcI9vNWGlZYT5cEkuSU2FIHHzJJN2[nO2cnH0[UBi\nSncjCzJJRwKDJ2IHjyd{BjgSCobIXvdoV{[2WwY3WgZZN{[XluIFnDOVA:OS54N988US=>	MWm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDB7NUCxPEc,OjRyOUWwNVg9N2F-
SNU16	MlX5R5l1d3SxeHnjbZR6KGG\|c3H5		NWnNVFV4PzJiaILz		NW\ZfW4yS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hW06XMU[gZ4VtdHNiYYPz[ZN{\WRiYYOg[5Jwf3SqIHnubIljcXSrb36gZYZ1\XJiN{KgbJJ{KGK7IF3UWEBie3OjeTygTWM2OD1yLkG0Nu69VQ>?	NV7SfZBbRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4NFU1PDZpPkK1PFA2PDR4PD;hQi=>
High5	Mn:0SpVv[3Srb36gZZN{[Xl?		MnvLNlQhcHK\|		NHK5UlVKdmirYnn0bY9vKG:oIILlZ49u[mmwYX70JIh2dWGwIFjERWMzKGW6cILld5Nm\CCrbjDiZYN2dG:4aYL1d{Bqdm[nY4Tl[EBqdnOnY4SgTIlocDViY3XscJMhfXOrbnegRYMuVHm\|LWT5dk1NgXNiKHXwd4ltd25vYXPleJltMS2DTVOgZZMhe3Wkc4TyZZRmKGGodHXyJFI1KGi{czDifUBndHWxcnXzZ4Vv[2ViYYPzZZktKEmFNUC9NE4yP87:TR?=	Ml\WQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6MEW0OFYoRjJ3OEC1OFQ3RC:jPh?=
High5	NFPxO2RHfW6ldHnvckBie3OjeR?=		NHrhRnE{KGi{cx?=		Ml\2TY5pcWKrdHnvckBw\iC{ZXPvcYJqdmGwdDDoeY1idiCKRFHDN{BmgHC{ZYPz[YQhcW5iYnHjeYxwfmm{dYOgbY5n\WO2ZXSgbY5{\WO2IFjp[4g2KGOnbHzzJJV{cW6pIFHjMWx6ey2WeYKtUJl{KCincIPpcI9vNWGlZYT5cEkuSU2FIHHzJJN2[nO2cnH0[UBi\nSncjCzJIhzeyCkeTDmcJVwemW\|Y3XuZ4Uh[XO\|YYmsJGlEPTB;MD6zOu69VQ>?	NYT4b5ZwRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4NFU1PDZpPkK1PFA2PDR4PD;hQi=>
High5	M2DDb2Z2dmO2aX;uJIF{e2G7		MWWyOEBpenN?		NWS5WnUzUW6qaXLpeIlwdiCxZjDy[YNwdWKrbnHueEBpfW2jbjDISGFEOSCneIDy[ZN{\WRiaX6gZoFkfWyxdnnyeZMhcW6oZXP0[YQhcW6\|ZXP0JGhq\2h3IHPlcIx{KHW\|aX7nJGFkNUy7cz3UfZIuVHm\|IDjldJNqdG:wLXHj[ZR6dClvQV3DJIF{KHO3YoP0doF1\SCjZoTldkAzPCCqcoOgZpkh\my3b4Lld4NmdmOnIHHzd4F6NCCLQ{WwQVAvOzoQvF2=	NYCxTGFrRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4NFU1PDZpPkK1PFA2PDR4PD;hQi=>
HCT116	NX24flZ6S3m2b4TvfIlkcXS7IHHzd4F6		MXq3NkBpenN?		NE[5SYpEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBJS1RzMU[gZ4VtdHNiYYPz[ZN{\WRiYYOg[5Jwf3SqIHnubIljcXSrb36gZYZ1\XJiN{KgbJJ{KGK7IF3UWEBie3OjeTygTWM2OD1yLkO5Ou69VQ>?	MoHpQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6MEW0OFYoRjJ3OEC1OFQ3RC:jPh?=
SW620	M1i2O2N6fG:2b4jpZ4l1gSCjc4PhfS=>		MVm3NkBpenN?		MX3DfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDTW\|YzOCClZXzsd{Bie3Onc4Pl[EBieyCpcn;3eIghcW6qaXLpeIlwdiCjZoTldkA4OiCqcoOgZpkhVVSWIHHzd4F6NCCLQ{WwQVAvPDF7zszN	NYLVV5F7RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4NFU1PDZpPkK1PFA2PDR4PD;hQi=>
MKN45	MlXWR5l1d3SxeHnjbZR6KGG\|c3H5		MXS3NkBpenN?		NULo[ohwS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hVUuQNEWgZ4VtdHNiYYPz[ZN{\WRiYYOg[5Jwf3SqIHnubIljcXSrb36gZYZ1\XJiN{KgbJJ{KGK7IF3UWEBie3OjeTygTWM2OD1yLk[x{txO	MoH3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6MEW0OFYoRjJ3OEC1OFQ3RC:jPh?=
Hep3B	NHvQW2ZEgXSxdH;4bYNqfHliYYPzZZk>		MnzDO\|IhcHK\|		M{PMNWN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGhmeDOEIHPlcIx{KGG\|c3Xzd4VlKGG\|IHfyc5d1cCCrbnjpZol1cW:wIHHmeIVzKDd{IHjyd{BjgSCPVGSgZZN{[XluIFnDOVA:OC56MkROwG0>	NVS3Zld{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4NFU1PDZpPkK1PFA2PDR4PD;hQi=>
HepG2	NYjveW1XS3m2b4TvfIlkcXS7IHHzd4F6		NUDxSnQ2PzJiaILz		Mm\5R5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gTIVxTzJiY3XscJMh[XO\|ZYPz[YQh[XNiZ4Lve5RpKGmwaHnibZRqd25iYX\0[ZIhPzJiaILzJIJ6KE2WVDDhd5NigSxiSVO1NF0xNjh5Nt88US=>	NFX4O\|k9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUiwOVQ1Pid-MkW4NFU1PDZ:L3G+
SNU5	MX;DfZRwfG:6aXPpeJkh[XO\|YYm=		MVe3NkBpenN?		M3fMN2N6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJHNPXTViY3XscJMh[XO\|ZYPz[YQh[XNiZ4Lve5RpKGmwaHnibZRqd25iYX\0[ZIhPzJiaILzJIJ6KE2WVDDhd5NigSxiSVO1NF0yNjByOd88US=>	MmO3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6MEW0OFYoRjJ3OEC1OFQ3RC:jPh?=
A549	MljmR5l1d3SxeHnjbZR6KGG\|c3H5		MmfVO\|IhcHK\|		NHO4OHFEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBCPTR7IHPlcIx{KGG\|c3Xzd4VlKGG\|IHfyc5d1cCCrbnjpZol1cW:wIHHmeIVzKDd{IHjyd{BjgSCPVGSgZZN{[XluIFnDOVA:Oi5yON88US=>	MlXzQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6MEW0OFYoRjJ3OEC1OFQ3RC:jPh?=
SJSA1	Mn60R5l1d3SxeHnjbZR6KGG\|c3H5		NVrIUHVDPzJiaILz		Mmj0R5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gV2pUSTFiY3XscJMh[XO\|ZYPz[YQh[XNiZ4Lve5RpKGmwaHnibZRqd25iYX\0[ZIhPzJiaILzJIJ6KE2WVDDhd5NigSxiSVO1NF0{NjZ{NN88US=>	MkDhQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6MEW0OFYoRjJ3OEC1OFQ3RC:jPh?=
MHCC97H	MnHrR5l1d3SxeHnjbZR6KGG\|c3H5		NIK5b4w4OiCqcoO=		M{TmSmN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJG1JS0N7N1igZ4VtdHNiYYPz[ZN{\WRiYYOg[5Jwf3SqIHnubIljcXSrb36gZYZ1\XJiN{KgbJJ{KGK7IF3UWEBie3OjeTygTWM2OD12LkW2N:69VQ>?	M1z1TVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEC1OFQ3Lz5{NUiwOVQ1PjxxYU6=
PANC1	NXfMdWMxS3m2b4TvfIlkcXS7IHHzd4F6		MVe3NkBpenN?		Mo\KR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gVGFPSzFiY3XscJMh[XO\|ZYPz[YQh[XNiZ4Lve5RpKGmwaHnibZRqd25iYX\0[ZIhPzJiaILzJIJ6KE2WVDDhd5NigSxiSVO1NF0zPi55N{VOwG0>	MWG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPThyNUS0Okc,OjV6MEW0OFY9N2F-
U937	NIrzW41HfW6ldHnvckBie3OjeR?=	NHXIWGkyOCC3TR?=	M3fjOVI1KGi{cx?=		M3W5ZmlvcGmkaYTpc44hd2ZiSFTBR\|MhcW5iaIXtZY4hXTl\|NzDj[YxteyCjc4Pld5Nm\CCjczDpcoNz\WG\|ZTDpckBpcXO2b37lJGg{KGy7c3nu[U06KGGlZYT5cIF1cW:wIHH0JFExKHWPIHnuZ5Vj[XSnZDDmc5IhOjRiaILzJIJ6KFenc4Tldo4h[myxdITpcochdWW2aH;k	MnrMQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ{OEezNVAoRjJ4Mki3N\|ExRC:jPh?=
PC3	MlzvSpVv[3Srb36gZZN{[Xl?	NVnXeWZ6OTBidV2=	MYGyOEBpenN?		M4PLbGlvcGmkaYTpc44hd2ZiSFTBR\|MhcW5iaIXtZY4hWEN\|IHPlcIx{KGG\|c3Xzd4VlKGG\|IHnuZ5Jm[XOnIHnuJIhqe3SxbnWgTFMhdHm\|aX7lMVkh[WOndInsZZRqd25iYYSgNVAhfU1iaX7jeYJifGWmIH\vdkAzPCCqcoOgZpkhX2W\|dHXyckBjdG:2dHnu[{Bu\XSqb3S=	NYP3bmNyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[yPFc{OTBpPkK2Nlg4OzFyPD;hQi=>
U937	MoT5SpVv[3Srb36gZZN{[Xl?	MVKxNEB2VQ>?	NGTQXpczPCCqcoO=		NH31VnRKdmirYnn0bY9vKG:oIFjERWMhcW5iaIXtZY4hXTl\|NzDj[YxteyCjc4Pld5Nm\CCjczDy[YR2[3Srb36gbY4h[3mlbHnuJGUh\XiycnXzd4lwdiCrbjDheEAyOCC3TTDpcoN2[mG2ZXSg[o9zKDJ2IHjyd{BjgSCZZYP0[ZJvKGKub4T0bY5oKG2ndHjv[C=>	MmjtQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ{OEezNVAoRjJ4Mki3N\|ExRC:jPh?=
Sf9	MWXGeY5kfGmxbjDhd5NigQ>?		Mn:zNVAhdWmwcx?=		NYTzWlBSUW6qaXLpeIlwdiCxZjDy[YNwdWKrbnHueEBnfWyuIHzlcod1cCCqdX3hckBENXSncn3pcoFtKE[OQVeteIFo\2WmIFjERWMyOSCneIDy[ZN{\WRiaX6gZoFkfWyxdnnyeZMhcW6oZXP0[YQhW2Z7IHPlcIx{KHW\|aX7nJGJw[y2OeYOo[ZB{cWyxbj3BZ{kuSU2FIHHzJJN2[nO2cnH0[UBxemW2cnXheIVlKG[xcjCxNEBucW6\|IH\vcIxwf2WmIHL5JJN2[nO2cnH0[UBi\GSrdHnvckBjgSCobIXvdo9u\XS{aXOgcYV1cG:mLDDJR\|UxRTBwNUpOwG0>	NXP0W21ORGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMki1NFE2OTRpPkK4OVAyPTF2PD;hQi=>
TC32	NHvzenNyUFSVIHHzd4F6				M2m5epFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCWQ{OyJINmdGy\|	MVK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
DAOY	MWfxTHRUKGG\|c3H5				M{DobpFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCGQV;ZJINmdGy\|	MYK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
SJ-GBM2	M4TpTJFJXFNiYYPzZZk>				MXPxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhW0pvR1LNNkBk\Wyucx?=	MXS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
A673	NXHsd3lveUiWUzDhd5NigQ>?				NFrNO2lyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiQU[3N{Bk\Wyucx?=	MXu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
SK-N-MC	M4rxNJFJXFNiYYPzZZk>				MlnNdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKFONLV6tUWMh[2WubIO=	MUm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
BT-37	NXqwU\|ZQeUiWUzDhd5NigQ>?				MlHJdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKEKWLUO3JINmdGy\|	Mnu3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
NB-EBc1	NVzEO4RNeUiWUzDhd5NigQ>?				M331UpFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCQQj3FRoMyKGOnbHzz	MX[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
U-2 OS	NHvCbphyUFSVIHHzd4F6				NVnvc2JFeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IGWtNkBQWyClZXzsdy=>	NXTXW\|RIRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
Saos-2	M3;YUZFJXFNiYYPzZZk>				NWG4[Yc4eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IGPhc5MuOiClZXzsdy=>	MVW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
SK-N-SH	NFvUdnFyUFSVIHHzd4F6				Mn3adWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKFONLV6tV2gh[2WubIO=	NILRSYc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
NB1643	MWLxTHRUKGG\|c3H5				M3fXVpFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCQQkG2OFMh[2WubIO=	M4nOZlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
LAN-5	MlXPdWhVWyCjc4PhfS=>				MVXxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhVEGQLUWgZ4VtdHN?	NGGy[FQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
BT-12	NVu3fGNKeUiWUzDhd5NigQ>?				MoTUdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKEKWLUGyJINmdGy\|	NWTZRZRbRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
Rh18	MWPxTHRUKGG\|c3H5				M1uweZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCUaEG4JINmdGy\|	M4raWVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
OHS-50	M{P2bJFJXFNiYYPzZZk>				Ml7sdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKE:KUz21NEBk\Wyucx?=	NXnzN5EzRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
RD	NH\CfJpyUFSVIHHzd4F6				M2Hn[pFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCURDDj[Yxtew>?	MWm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
MG 63 (6-TG R)	MWXxTHRUKGG\|c3H5				MojLdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKE2JIE[zJEg3NVSJIGKpJINmdGy\|	NYnFfWRHRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
fibroblast cells	MX\xTHRUKGG\|c3H5				MkfkdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKGOxboTyc4whUGhid3ns[EB1gXCnIH\pZpJw[myjc4SgZ4VtdHN?	MlPtQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
Rh41	M3P0NZFJXFNiYYPzZZk>				NEjsUJFyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiUni0NUBk\Wyucx?=	NIPsXpI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
A673	NE\kZ3RyUFSVIHHzd4F6				MUTxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBEd26oaYLtZZRwenlic3Py[YVvKG[xcjDBOlc{KGOnbHzzLS=>	MWW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
DAOY	NISyS4tyUFSVIHHzd4F6				NEPYTo1yUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBFSU:\IHPlcIx{	MXS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
SJ-GBM2	MkTldWhVWyCjc4PhfS=>				NFPHZXZyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBUUi2JQl2yJINmdGy\|	MlHoQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
U-2 OS	NWjI[4tZeUiWUzDhd5NigQ>?				MmDadWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohS2:wZnnycYF1d3K7IIPjdoVmdiCob4KgWU0zKE:VIHPlcIx{	NEe4eYk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
RD	NUe0NJRseUiWUzDhd5NigQ>?				MXfxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBEd26oaYLtZZRwenlic3Py[YVvKG[xcjDSSEBk\Wyucx?=	NYC3XFFTRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
Rh18	M3vETJFJXFNiYYPzZZk>				MlHQdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohS2:wZnnycYF1d3K7IIPjdoVmdiCob4KgVogyQCClZXzsdy=>	MX[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
Rh30	NIrsSIhyUFSVIHHzd4F6				M{TRSJFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJHJpOzBiY3XscJM>	M{PsXlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
Sf9	NY\rZmVpTnWwY4Tpc44h[XO\|YYm=				MVTJcohq[mm2aX;uJGF{e2G7OjDISGFEKGmwaHnibZRqd25iYYPzZZl{KHencnWgdIVz\m:{bXXkJIJ6KFKnYXP0bY9vKEKrb3zv[5khS2:{cD6gLG1idH[ncn6sJHBiNilidYPpcochcXOxbHH0[YQhcHWvYX6sJJJm[2:vYnnuZY51KG[3bHytcIVv\3SqIFjERWMyKGGwZDCtOkBnem:vIHGgZoFkfWyxdnnyeZMh\XiycnXzd4lwdiC\|eYP0[Y0hcW5iU3[5JINmdGy\|LDDJR\|UxRTBwMUCy{txO	MXu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyyO\|I6QDBxJ{7DbGVOSkx:L3G+
HCT116	NU\STWJySW62aYDyc4xq\mW{YYTpeoUh[XO\|YYm=		MXy0PEBpenN?		Ml\QRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6\|dDDoeY1idiCKQ2SxNVYh[2WubIOgZZN{\XO\|ZXSgZZMhemWmdXP0bY9vKGmwIHPlcIwhfmmjYnnsbZR6KGGodHXyJFQ5KGi{czDifUBOXFRiYYPzZZktKEmFNUC9NU4zPM7:TR?=	MnfCQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNlczQThyLze+R4hGVUKOPD;hQi=>
MCF7	MWTBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>?		NFnPeZc4OiCqcoO=		MorXRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6\|dDDoeY1idiCPQ1[3JINmdGy\|IHHzd4V{e2WmIHHzJJJm\HWldHnvckBqdiClZXzsJJZq[WKrbHn0fUBi\nSncjC3NkBpenNiYomgUXRVKGG\|c3H5MEBKSzVyPUKuOFnPxE1?	MlrlQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNlczQThyLze+R4hGVUKOPD;hQi=>
HeLa	MUPBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>?		NGPMUlM1QCCqcoO=		MojTRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6\|dDDoeY1idiCKZVzhJINmdGy\|IHHzd4V{e2WmIHHzJJJm\HWldHnvckBqdiClZXzsJJZq[WKrbHn0fUBi\nSncjC0PEBpenNiYomgUXRVKGG\|c3H5MEBKSzVyPUOuN\|LPxE1?	MnK1QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNlczQThyLze+R4hGVUKOPD;hQi=>
HeLa	NVTk[JdmSW62aYDyc4xq\mW{YYTpeoUh[XO\|YYm=		MYK3NkBpenN?		NFfuVllCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFjlUIEh[2WubIOgZZN{\XO\|ZXSgZZMhemWmdXP0bY9vKGmwIHPlcIwhfmmjYnnsbZR6KGGodHXyJFczKGi{czDifUBOXFRiYYPzZZktKEmFNUC9N{41Os7:TR?=	Mny1QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNlczQThyLze+R4hGVUKOPD;hQi=>
HCT116	MnT2RY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl?		MYq3NkBpenN?		MUnBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKEiFVEGxOkBk\WyuczDhd5Nme3OnZDDhd{Bz\WS3Y4Tpc44hcW5iY3XscEB3cWGkaXzpeJkh[W[2ZYKgO\|IhcHK\|IHL5JG1VXCCjc4PhfUwhUUN3ME2zMlUy\|ryP	Mm[wQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNlczQThyLze+R4hGVUKOPD;hQi=>
HepG2	MnjpRY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl?		NIrUTlM1QCCqcoO=		MnvXRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6\|dDDoeY1idiCKZYDHNkBk\WyuczDhd5Nme3OnZDDhd{Bz\WS3Y4Tpc44hcW5iY3XscEB3cWGkaXzpeJkh[W[2ZYKgOFghcHK\|IHL5JG1VXCCjc4PhfUwhUUN3ME20MlA2\|ryP	MV:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyyO\|I6QDBxJ{7DbGVOSkx:L3G+
HepG2	NXvDR\|RXSW62aYDyc4xq\mW{YYTpeoUh[XO\|YYm=		NHfZOVE4OiCqcoO=		NEHxXXdCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFjldGczKGOnbHzzJIF{e2W\|c3XkJIF{KHKnZIXjeIlwdiCrbjDj[YxtKH[rYXLpcIl1gSCjZoTldkA4OiCqcoOgZpkhVVSWIHHzd4F6NCCLQ{WwQVQvOjYQvF2=	MlfnQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNlczQThyLze+R4hGVUKOPD;hQi=>
HepG2	MnztRY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl?		NEDZb4QzPCCqcoO=		NEj1c\|JCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFjldGczKGOnbHzzJIF{e2W\|c3XkJIF{KHKnZIXjeIlwdiCrbjDj[YxtKH[rYXLpcIl1gSCjZoTldkAzPCCqcoOgZpkhVVSWIHHzd4F6NCCLQ{WwQVUvPzoQvF2=	NX3xU4Z2RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOjd{OUiwM{c,S2iHTVLMQE9iRg>?
A549	Mn\zRY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl?		MUW3NkBpenN?		NH[zRYRCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFG1OFkh[2WubIOgZZN{\XO\|ZXSgZZMhemWmdXP0bY9vKGmwIHPlcIwhfmmjYnnsbZR6KGGodHXyJFczKGi{czDifUBOXFRiYYPzZZktKEmFNUC9NVEvQDgQvF2=	M1L0Z\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFI4Ojl6MD:nQmNpTU2ETEyvZV4>
A549	MYDBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>?		MoH5OFghcHK\|		Mm[3RY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6\|dDDoeY1idiCDNUS5JINmdGy\|IHHzd4V{e2WmIHHzJJJm\HWldHnvckBqdiClZXzsJJZq[WKrbHn0fUBi\nSncjC0PEBpenNiYomgUXRVKGG\|c3H5MEBKSzVyPUG0MlU4\|ryP	NXWwdZRqRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOjd{OUiwM{c,S2iHTVLMQE9iRg>?
HCT116	M{i5WmFvfGmycn;sbYZmemG2aY\lJIF{e2G7		Mn;sNlQhcHK\|		MWPBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKEiFVEGxOkBk\WyuczDhd5Nme3OnZDDhd{Bz\WS3Y4Tpc44hcW5iY3XscEB3cWGkaXzpeJkh[W[2ZYKgNlQhcHK\|IHL5JG1VXCCjc4PhfUwhUUN3ME2yPU43Qc7:TR?=	NYfsTmpTRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOjd{OUiwM{c,S2iHTVLMQE9iRg>?
HeLa	NULaNGpiSW62aYDyc4xq\mW{YYTpeoUh[XO\|YYm=		NIjPU2ozPCCqcoO=		MljQRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6\|dDDoeY1idiCKZVzhJINmdGy\|IHHzd4V{e2WmIHHzJJJm\HWldHnvckBqdiClZXzsJJZq[WKrbHn0fUBi\nSncjCyOEBpenNiYomgUXRVKGG\|c3H5MEBKSzVyPUSzMljPxE1?	NI[5Z\|M9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwzPzJ7OECvK\|5EcEWPQly8M4E,

Click to View More Cell Line Experimental Data

Assay

Methods	Test Index	PMID

Western blot	Bad / Bid / Bak / Puma / Bax / Cleaved caspase-9 / Cleaved caspase-3 / Cleaved PARP ; Ac-H3 / Ac-H4 / Ac-tubulin	27551526 29186204
Immunofluorescence	E-cadherin / ZEB1 ; Nanog / MHC	25872941 26240433
Growth inhibition assay	Cell viability	26378038

In vivo

MGCD0103 significantly inhibites growth of human tumor xenografts in nude mice and the antitumor activity correlated with induction of histone acetylation in tumors. P.O. administration of MGCD0103 (2HBr salt) significantly decreases growth of implanted advanced A549 tumors in nude mice in a dose-dependent manner after 13 days of daily administration. MGCD0103 (170 mg/kg for 2HBr salt, corresponding to 120 mg/kg of free base) significantly blockes growth of tumors compared with vehicle treatment alone with no change in body weight. In addition, MGCD0103 does not reduce WBC counts and is well tolerated. MGCD0103 is also orally active in many other human tumor xenograft models including NSCLC H1437. MGCD0103 at 80 mg/kg (free base) almost completely blocks the growth of H1437 tumors after 13 days of daily p.o. administration with no reduction of body weight in animals. ^[1] MGCD0103 reduces pulmonary arterial pressure more dramatically than tadalafil, a standard-of-care therapy for human pulmonary hypertension that functions as a vasodilator. Moreover, MGCD0103 improves pulmonary artery acceleration time and reduced systolic notching of the pulmonary artery flow envelope, which suggests a positive impact of the HDAC inhibitor on pulmonary vascular remodeling and stiffening. ^[2]

Protocol (from reference)

Kinase Assay:^[1]	HDAC enzyme assay in vitro: The deacetylase enzyme assay is based on a homogeneous fluorescence release assay. Purified recombinant HDAC enzymes are incubated with MGCD0103 diluted in various concentrations for 10 minutes in assay buffer [25 mM HEPES (pH 8.0), 137 mM NaCl, 1 mM MgCl₂, 2.7 mM KCl] at room temperature. The substrate Boc-Lys(ε-Ac)-AMC is added to the reaction for further incubation at 37 °C. The concentration of the substrate and the incubation time varies for different isotypes of HDAC enzymes. A 20-min trypsin incubation at room temperature allows the release of the fluorophore from the deacetylated substrate. The fluorescent signal is detected by fluorometer at excitation of 360 nm, emission of 470 nm, and cutoff at 435 nm.
Cell Research:^[1]	Cell lines: Human mammary epithelial cells (HMEC), human foreskin fibroblasts (MRHF) cells Concentrations: 0-60 μM Incubation Time: 72 hours Method: Human mammary epithelial cells (HMEC) and human foreskin fibroblasts (MRHF) cells in 96-well plates are incubated with MGCD0103 at various concentrations for 72 hours at 37 °C in 5% CO₂. MTT is added at a final concentration of 0.5 mg/ml and incubated with the cells for 4 hours before an equal volume of solubilization buffer [50% N,N-dimethylformamide, 20% SDS (pH 4.7)] is added. After overnight incubation, solubilized dye is quantified by reading at 570 nm using a reference at 630 nm. Absorbance values are converted to cell numbers according to a standard growth curve of the relevant cell line. The concentration which reduces cell numbers to 50% relative to DMSO-treated cells is determined as MTT IC5 (Only for Reference)
Animal Research:^[1]	Animal Models: Female CD-1 nude mice bearing H1437 tumors Dosages: 80 mg/kg Administration: Administered via p.o. (Only for Reference)

References

Solubility (25°C)

In vitro	DMSO	13 mg/mL (32.79 mM)
	Water	Insoluble
	Ethanol	Insoluble
In vivo	Add solvents to the product individually and in order (Data is from Selleck tests instead of citations): 30% PEG400+0.5% Tween80+5% Propylene glycol For best results, use promptly after mixing. Click to purchase: PEG400 Tween 80	30mg/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	396.44
Formula	C₂₃H₂₀N₆O
CAS No.	726169-73-9
Storage	3 years	-20°C	powder
Storage	2 years	-80°C	in solvent
Smiles	C1=CC=C(C(=C1)N)NC(=O)C2=CC=C(C=C2)CNC3=NC=CC(=N3)C4=CN=CC=C4

Download Mocetinostat (MGCD0103) SDF

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:μL Number of animals:

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Working concentration: mg/ml;

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.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, 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
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Molarity Calculator

Dilution Calculator Molecular Weight Calculator

Clinical Trial Information

NCT Number	Recruitment	Interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT04299113	Recruiting	Drug: Vinorelbine\|Drug: Mocetinostat	Rhabdomyosarcoma	Jonsson Comprehensive Cancer Center\|Mirati Therapeutics Inc.\|Phase One Foundation	May 14 2020	Phase 1
NCT02993991	Withdrawn	Drug: Mocetinostat\|Biological: Durvalumab	Squamous Cell Carcinoma Head And Neck\|Squamous Cell Carcinoma Mouth\|Resectable Squamous Cell Carcinoma of Oral Cavity	University Health Network Toronto\|Mirati Therapeutics Inc.\|AstraZeneca	October 10 2017	Phase 1
NCT02236195	Completed	Drug: Mocetinostat	Urothelial Carcinoma	Mirati Therapeutics Inc.	October 2014	Phase 2
NCT00666497	Terminated	Drug: Azacitidine\|Drug: MGCD0103	Acute Myeloid Leukemia (AML)\|Myelodysplastic Syndrome (MDS)	Mirati Therapeutics Inc.	June 2008	Phase 2
NCT00511576	Terminated	Drug: MGCD0103 & Docetaxel	Breast Cancer\|Lung Cancer\|Pulmonary Cancer\|Non-Small-Cell Lung Carcinoma\|Prostate Cancer\|Prostatic Cancer\|Gastric Cancer\|Stomach Cancer	Mirati Therapeutics Inc.	August 2007	Phase 1

(data from https://clinicaltrials.gov, updated on 2022-01-17)

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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