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Tivantinib (ARQ 197)

Name: Tivantinib (ARQ 197)
Brand: Selleck Chemicals
SKU: S2753
Rating: 5 (40 reviews)

Catalog No.S2753

For research use only.

Tivantinib (ARQ 197) is the first non-ATP-competitive c-Met inhibitor with K_i of 0.355 μM in a cell-free assay, little activity to Ron, and no inhibition to EGFR, InsR, PDGFRα or FGFR1/4. Tivantinib (ARQ 197) induces a G2/M arrest and apoptosis. Phase 3.

CAS No. 905854-02-6

Selleck's Tivantinib (ARQ 197) has been cited by 40 publications

Purity & Quality Control

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c-Met Signaling Pathway Map

Biological Activity

Description

Features

The first selective c-Met inhibitor to be advanced into human clinical trials.

Targets

c-Met ^[1]
(Cell-free assay)

0.355 μM(Ki)

In vitro

ARQ-197 has been shown to prevent HGF/c-met induced cellular responses in vitro. ARQ-197 possesses antitumor activity; inhibiting proliferation of A549, DBTRG and NCI-H441 cells with IC50 of 0.38, 0.45, 0.29 μM. Treatment with ARQ-197 results in a decrease in phosphorylation of the MAPK signaling cascade and prevention of invasion and migration. In addition, ectopic expression of c-Met in NCI-H661, a cell line having no endogenous expression of c-Met, causes it to acquire an invasive phenotype that is also suppressed by ARQ-197. Although the addition of increasing concentrations of ARQ-197 does not significantly affect the K_m of ATP, exposure of c-Met to 0.5 μM ARQ-197 decreased the V_max of c-Met by approximately 3-fold. The ability of ARQ-197 to decrease the V_max without affecting the Km of ATP confirmed that ARQ-197 inhibits c-Met through a non–ATP-competitive mechanism and may therefore account for its high degree of kinase selectivity. ARQ-197 prevents human recombinant c-Met with a calculated inhibitory constant K_i of approximately 355 nM. Although the highest concentration of ATP used is 200 μM, the potency of ARQ-197 against c-Met is not reduced by using concentrations of ATP up to 1 mM. ARQ-197 blocks c-Met phosphorylation and downstream c-Met signaling pathways. ARQ-197 suppresses constitutive and ligand-mediated c-Met autophosphorylation and, by extension, c-Met activity, in turn leading to the inhibition of downstream c-Met effectors. ARQ-197 induction of caspase-dependent apoptosis is increased in c-Met–expressing human cancer cells including HT29, MKN-45, and MDA-MB-231 cells.^[1]^[2]

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Formulation	Activity Description	PMID

MNK-45	MmraT4lv[XOnIHHzd4F6	NIW3T4x,OTBizszN		NV;MTXBScW6qaXLpeJMh[y2PZYSgdIhwe3Cqb4L5cIF1cW:wIHHu[EBld3ewc4Ty[YFuKGNvTXX0JJNq\26jbHnu[{Bx[XSqd3H5dy=>	M3PhWVIxPDh2MEG4
HT29	MofTT4lv[XOnIHHzd4F6	NFnrVoR,OTBizszN		MmHlbY5pcWKrdIOgZ{1O\XRicHjvd5Bpd3K7bHH0bY9vKGGwZDDkc5dve3S{ZXHtJIMuVWW2IIPp[45idGmwZzDwZZRpf2G7cx?=	MlXZNlA1QDRyMUi=
MDA-MB-231	MV3LbY5ie2ViYYPzZZk>	NIW4[pV,OTBizszN		MVLpcohq[mm2czDjMW1mfCCyaH;zdIhwenmuYYTpc44h[W6mIHTve45{fHKnYX2gZ{1O\XRic3nncoFtcW6pIIDheIh4[Xm\|	NED3XWwzODR6NECxPC=>
NCI-H441	M1PqSWtqdmG\|ZTDhd5NigQ>?	NIL2WYJ,OTBizszN		Mn\SbY5pcWKrdIOgZ{1O\XRicHjvd5Bpd3K7bHH0bY9vKGGwZDDkc5dve3S{ZXHtJIMuVWW2IIPp[45idGmwZzDwZZRpf2G7cx?=	NWX3VZVKOjB2OESwNVg>
SK-MEL-28	MmeyS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	M{n6WlM{KM7:TR?=		M2HiUmlEPTB-M{Og{txO	MoLxNlA1QDRyMUi=
NCI-H661	NV7pUpJ[T3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	M2r3U\|M{KM7:TR?=		MlLhTWM2OD5\|MzFOwG0>	Ml7CNlA1QDRyMUi=
NCI-H446	NEjhXWZIem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	MYqzN{DPxE1?		NFHVOYtKSzVyPUeg{txO	NFjVeHgzODR6NECxPC=>
MDA-MB-231	MmXMS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	MoP4N\|Mh\|ryP		NH3iUFdKSzVyPUCuOVUh\|ryP	MXqyNFQ5PDBzOB?=
DLD-1	NYL0TJQyT3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	M4\aPFM{KM7:TR?=		NWSyXpNQUUN3ME2wMlU{KM7:TR?=	NFXw[XgzODR6NECxPC=>
A549	MlO5S5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	M4XFSVM{KM7:TR?=		M3;Ze2lEPTB;MD61PUDPxE1?	MV:yNFQ5PDBzOB?=
SK-OV-3	NWT3Xm9FT3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	M4PhWlM{KM7:TR?=		MmTYTWM2OD1yLk[2JO69VQ>?	NYSwRpdyOjB2OESwNVg>
NCI-H460	MYLHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?	MYOzN{DPxE1?		NV3uOWhzUUN3ME2wMlYh\|ryP	NHT1e5AzODR6NECxPC=>
A375	Ml\ES5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	NF;pN3U{OyEQvF2=		MlTRTWM2OD1yLkSyJO69VQ>?	NEnNdJgzODR6NECxPC=>
NCI-H441	M1H6Nmdzd3e2aDDpcohq[mm2b4L5JIF{e2G7	MmjMN\|Mh\|ryP		MXvJR\|UxRTBwMzFOwG0>	NGHkfnUzODR6NECxPC=>
HT29	NHn3XFFIem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	NHPCeWQ{OyEQvF2=		M4W1fmlEPTB;MD60PUDPxE1?	NIHjU\|UzODR6NECxPC=>
MKN-45	Mn22S5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	Mm\JN\|Mh\|ryP		MXnJR\|UxRTBwNUig{txO	MWCyNFQ5PDBzOB?=
HT29	MVPBdI9xfG:\|aYOgZZN{[Xl?	MWL+NVAh\|ryP		MUnzbYdvcW[rY3HueIx6KGmwZIXj[ZMh[XCxcITvd4l{KGK7IEiwMVkxLS5?	NVqzc5ZqOjB2OESwNVg>
MKN-45	M3XlUmFxd3C2b4Ppd{Bie3OjeR?=	NUfqSFdnhjFyIN88US=>		MoW4d4lodmmoaXPhcpRtgSCrbnT1Z4V{KGGyb4D0c5NqeyCkeTC4NE06OCVw	M2foeFIxPDh2MEG4
MDA-MB-231	MXvBdI9xfG:\|aYOgZZN{[Xl?	MYH+NVAh\|ryP		NHXOVYpud2Snc4TsfUBqdmS3Y3XzJIFxd3C2b4Ppd{BjgSB\|NTWu	M{HSfVIxPDh2MEG4
MDA-MB-231/TGL	M{ewfWdzd3e2aDDpcohq[mm2b4L5JIF{e2G7	M373O54yODBizszN		MYXHTVUxRTFwMjFOwG0>	M{LWXlIzODJ5Nkmw
1833/TGL	NWLkc2J{T3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	MVf+NVAxKM7:TR?=		MlnnS2k2OD1\|Lkeg{txO	NUPm[pY{OjJyMke2PVA>
EBC1	NYPidGZlS3m2b4TvfIlkyqCjc4PhfS=>	NXvBU4JshjFyIN88US=>		NWG3[YtjcW6qaXLpeJMhfGinIHPlcIwh\3Kxd4ToMi=>	NE\PdZMzOzV7OEK3Oi=>
SNU638	NVrF[JN{S3m2b4TvfIlkyqCjc4PhfS=>	NEP5UY5,OTBizszN		NUDsNZJ7cW6qaXLpeJMhfGinIHPlcIwh\3Kxd4ToMi=>	MXqyN\|U6QDJ5Nh?=
A549	MoG5R5l1d3SxeHnjxsBie3OjeR?=	Mni1glExKM7:TR?=		NV[4[ng1dm:2IHHm[oVkfA>?	Mn;RNlM2QTh{N{[=
H460	MXzDfZRwfG:6aXRCpIF{e2G7	NH\1O\|d,OTBizszN		MX7uc5Qh[W[oZXP0	NUTDN2kyOjN3OUiyO\|Y>
HCC827	M{XMbWN6fG:2b4jpZ:Kh[XO\|YYm=	NHLiWFR,OTBizszN		NWPOPWVMdm:2IHHm[oVkfA>?	MlHuNlM2QTh{N{[=
A549	MnvZSpVv[3Srb36gZZN{[Xl?	MoLqNVAh\|ryP		MXvkbZNzfXC2czDtbYNzd3S3YoXs[S=>	MoPZNlM2QTh{N{[=
EBC1	MYHGeY5kfGmxbjDhd5NigQ>?	MlnRNVAh\|ryP		MYTkbZNzfXC2czDtbYNzd3S3YoXs[S=>	MoPHNlM2QTh{N{[=
H460	MWnGeY5kfGmxbjDhd5NigQ>?	NHfTWpMyOCEQvF2=		MUfpcohq[mm2czD0eYJ2dGmwIIDvcJlu\XKrenH0bY9v	NFLZWoczPTNzM{CxNC=>
K562/VCR	NUHtWo9MS3m2b4TvfIlkyqCjc4PhfS=>	NELlSGR,OTBizszN		M1XTcZNpd3e\|IHP5eI91d3irYzDhZ5Rqfmm2eR?=	MV6yOVMyOzBzMB?=
CEM/VBL	M{jZZWN6fG:2b4jpZ:Kh[XO\|YYm=	MXn+NVAh\|ryP		M{TnUJNpd3e\|IHP5eI91d3irYzDhZ5Rqfmm2eR?=	M3j4[VI2OzF\|MEGw
U266	M2C2UGN6fG:2b4jpZ:Kh[XO\|YYm=	NXzZR3RKhjNizszNxsA>		NFrKbGRKSzVyPUGuNUDPxE1?	NW\adYFrOjV6MUCwNVM>
OPM-2	Mn3WR5l1d3SxeHnjxsBie3OjeR?=	MWL+N{DPxE4EoB?=		MkjzTWM2OD1zLkig{txO	NGq4cY4zPThzMECxNy=>
MM.1S	MkXyR5l1d3SxeHnjxsBie3OjeR?=	M3H4c54{KM7:TdMg		M4nnemlEPTB;MT62JO69VQ>?	M4PyRVI2QDFyMEGz
MM.1R	Mmr0S5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	MVqzJO69VcLi		MWrpcohq[mm2czDj[YxtKGe{b4f0bEBjgSB2OTW=	NGXWRnUzPThzMECxNy=>
RPMI-8226	NUP5cGt6S3m2b4TvfIlkyqCjc4PhfS=>	MnrMglMh\|ryPwrC=		NF3YRmVKSzVyPUCuPUDPxE1?	MUWyOVgyODBzMx?=
ANBL-6	M2HhUGN6fG:2b4jpZ:Kh[XO\|YYm=	Mn;ZNUDPxE4EoB?=		MXfpcoR2[2W\|IHPlcIwh\GWjdHigZpkhdW:{ZTD0bIFvKDVyJR?=	NVrpXHZyOjV6MUCwNVM>
ANLB-6/V10R	MmL1R5l1d3SxeHnjxsBie3OjeR?=	NU\3[4hzOSEQvF5CpC=>		MV7pcoR2[2W\|IHPlcIwh\GWjdHigZpkhdW:{ZTD0bIFvKDVyJR?=	M3HQW\|I2QDFyMEGz
KAS-6/1	NVu0W4Q4S3m2b4TvfIlkyqCjc4PhfS=>	MXGxJO69VcLi		MnjYbY5lfWOnczDj[YxtKGSnYYToJIJ6KG2xcnWgeIhidiB3MDW=	NVnxWXFKOjV6MUCwNVM>
KAS-6/V10R	MVHDfZRwfG:6aXRCpIF{e2G7	MnHNNUDPxE4EoB?=		NUjkWGxWcW6mdXPld{Bk\WyuIHTlZZRpKGK7IH3vdoUhfGijbjC1NEU>	NEjO[2gzPThzMECxNy=>
KAS-6/R10R	MXPDfZRwfG:6aXRCpIF{e2G7	MXKxJO69VcLi		NYDhV4lScW6mdXPld{Bk\WyuIHTlZZRpKGK7IH3vdoUhfGijbjC1NEU>	NWH1bVl{OjV6MUCwNVM>
8226/S	M1XuT2dzd3e2aDDpcohq[mm2b4L5JIF{e2G7	NGnX[5Q{KM7:TdMg		MXnpcohq[mm2czDj[YxtKGe{b4f0bEBjgSB3NDW=	NFrBOlUzPThzMECxNy=>
8226/LR-5	NX;ZdndmT3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	NWq0e4oyOyEQvF5CpC=>		MlXBbY5pcWKrdIOgZ4VtdCCpcn;3eIgh[nliNUSl	NYfHXFR[OjV6MUCwNVM>
Huh7	M1y5OGN6fG:2b4jpZ:Kh[XO\|YYm=	M4CyZZ41NjhizszNxsA>	MkHmSG1UVw>?	Mm\tTWM2OD17Lkmgcm0>	NYf5TGZyOjZ{NUmyOVA>
Hep3B	MWjDfZRwfG:6aXRCpIF{e2G7	M{\IPJ41NjhizszNxsA>	MXfEUXNQ	MmXuTWM2OD12NEiuO{BvVQ>?	NFrsTlczPjJ3OUK1NC=>
HepG2	MnvkR5l1d3SxeHnjxsBie3OjeR?=	MV3+OE45KM7:TdMg	NX7xdFVOTE2VTx?=	MnLlTWM2OD1zM{muO\|chdk1?	MWCyOlI2QTJ3MB?=
Chang	NHzNcpFEgXSxdH;4bYPDqGG\|c3H5	NYfwc\|EzhjRwODFOwG3DqA>?	NHzzXmtFVVOR	MlnnTWM2OD12NEiuO{BvVQ>?	MlzBNlYzPTl{NUC=
Huh7	MlXoSpVv[3Srb36gZZN{[Xl?	MY[xMlYh\|ryPwrC=	MkCxSG1UVw>?	MoHQZ4F2e2W\|IHGgS\|IwVSClZXzsJIN6[2ynIHHydoV{fA>?	MXGyOlI2QTJ3MB?=
Hep3B	NIHrPYVHfW6ldHnvckBie3OjeR?=	MUSxMlYh\|ryPwrC=	NWrNRYxiTE2VTx?=	MlHGZ4F2e2W\|IHGgS\|IwVSClZXzsJIN6[2ynIHHydoV{fA>?	NXH6Zo5SOjZ{NUmyOVA>
HepG2	MonzSpVv[3Srb36gZZN{[Xl?	MkHUNU43KM7:TdMg	NHXPUFRFVVOR	MoW4Z4F2e2W\|IHGgS\|IwVSClZXzsJIN6[2ynIHHydoV{fA>?	NGnwSFAzPjJ3OUK1NC=>
Chang	Ml7ISpVv[3Srb36gZZN{[Xl?	NEO3dFgyNjZizszNxsA>	NHfjXoVFVVOR	NFnHRlFk[XW\|ZYOgZUBIOi:PIHPlcIwh[3mlbHWgZZJz\XO2	M2D1VlI3OjV7MkWw
MHCC97L	Ml[2S5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	MnjDglExKM7:TR?=	M1r6cmROW09?	MVnJR\|UxRTNzNTDuUS=>	M3y4[\|I3PDV6OUWz
MHCC97H	NGHNO\|RIem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	NH70Wmd,OTBizszN	M4PMXGROW09?	NHfLUolKSzVyPUO2PQKBkSCwTR?=	NV\BcVlIOjZ2NUi5OVM>
Huh7	M2nrZ2dzd3e2aDDpcohq[mm2b4L5JIF{e2G7	MnHIglExKM7:TR?=	NWDJ[WRjTE2VTx?=	MYTJR\|UxRTJ4NTDuUS=>	M1izXVI3PDV6OUWz
HepG2	Ml;ZS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	MXX+NVAh\|ryP	NHvvN4tFVVOR	MWXJR\|UxRTN7MjDuUS=>	NInCV4IzPjR3OEm1Ny=>
MHCC97L	M2XreWZ2dmO2aX;uJIF{e2G7	Mn3sNUDPxE4EoB?=	NUjnemZ5TE2VTx?=	M17xfolv\HWlZYOgcYlkem:2dXL1cIV{KGSncH;sfY1memm8YYTpc44>	MnXsNlY1PTh7NUO=
Huh7	NYXMb4tUTnWwY4Tpc44h[XO\|YYm=	NE\X[G8yKM7:TdMg	MnrHSG1UVw>?	MWDpcoR2[2W\|IH3pZ5JwfHWkdXzld{Bl\XCxbInt[ZJqgmG2aX;u	NEP1ZVUzPjR3OEm1Ny=>
MHCC97L	MVvBdI9xfG:\|aYOgZZN{[Xl?	NUfOdYV5OSEQvF5CpC=>	M2G5cGROW09?	NFzJeHNqdmS3Y3XzJIFxd3C2b4Ppdy=>	M{jZOVI3PDV6OUWz
Huh7	MUTBdI9xfG:\|aYOgZZN{[Xl?	NGnIR\|IyKM7:TdMg	MlXBSG1UVw>?	Mn;wbY5lfWOnczDhdI9xfG:\|aYO=	NVTCbWZNOjZ2NUi5OVM>
C3H 10T1/2 mouse fibroblasts	M4m3OmtqdmG\|ZTDhd5NigQ>?	NIP6epozPSEQvF2=	M3zLcWROW09?	NWXmfY41emWmdXPld{BJcXO2b37lJGg{KGGwZDDIOEBi[2W2eXzheIlwdiCuZY\lcJPDqA>?	NWfPSVlSOjB3M{SzOFU>
H23	NX\aS4lkT3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	NFW2bVEzPSEQvF2=	NG\zZWZFVVOR	MUTzbYdvcW[rY3HueIx6KGmwaHnibZR{KGOnbHyg[5Jwf3SqLh?=	MljSNlA2OzR\|NEW=
WM35	MV7Hdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?	NXTRNWVOOTBizszN	Mn\3SG1UVw>?	M3jHUpNq\26rZnnjZY51dHliaX7obYJqfHNiY3XscEBoem:5dHiu	NXTibWJ3OjB3M{SzOFU>
NIH 3T3	MYTHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?	MoPzNVAh\|ryP	M3LXO2ROW09?	MYHkc4V{KG6xdDDoZZZmKGFic3nncolncWOjboSgbY5pcWKrdH;yfUBm\m[nY4S=	NHHzfZMzODV\|NEO0OS=>
H838	NGjEOnNIem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	NVH0[XNXOTBizszN	M1fBWGROW09?	NIi3bndld2W\|IH7veEBp[X[nIHGgd4lodmmoaXPhcpQhcW6qaXLpeI9zgSCnZn\lZ5Q>	MlPmNlA2OzR\|NEW=
H1395	NUnxR49RT3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	M2nxc\|ExKM7:TR?=	NFHUfoxFVVOR	NGTOWVBld2W\|IH7veEBp[X[nIHGgd4lodmmoaXPhcpQhcW6qaXLpeI9zgSCnZn\lZ5Q>	M4S2OlIxPTN2M{S1
Quiescent S2	NWTK[W93U2mwYYPlJIF{e2G7	MUCzNEDPxE1?	MXXEUXNQ	M2[3SYNwdXCuZYTlcJkh[WK{b3fheIV{KFSVQT3pcoR2[2WmIHj5dIVz[WOndInsZZRqd25ib3[gTFNMPG2nMzDobZN1d26ncx?=	NEj0TnQzOTVzOEmxOS=>
PC3	MV;BdI9xfG:\|aYOgZZN{[Xl?	NVfCSml4OjBizszN	M2\5VGROW09?	NYfwV3p1cW6mdXPld{BieG:ydH;zbZM>	NVvFdIFGOjF5MEmxN\|A>
Du145	NF;aNpFCeG:ydH;zbZMh[XO\|YYm=	M{jESVIxKM7:TR?=	MY\EUXNQ	M3nIOIlv\HWlZYOgZZBweHSxc3nz	MWKyNVcxQTF\|MB?=
LNCaP	NV:xUGlrSXCxcITvd4l{KGG\|c3H5	MWWyNEDPxE1?	MV\EUXNQ	NEPobXNqdmS3Y3XzJIFxd3C2b4Ppdy=>	M1ridFIyPzB7MUOw
LAPC-4	MmLsRZBweHSxc3nzJIF{e2G7	NEDhfm4zOCEQvF2=	MnHWSG1UVw>?	NYfEZlBzcW6mdXPld{BieG:ydH;zbZM>	NFTLToUzOTdyOUGzNC=>
LNCaP	NV;OXolSTnWwY4Tpc44h[XO\|YYm=	NYjNVGxROjBizszN	M3zLPWROW09?	NWThcVdZ\GWlcnXhd4V{KFCVQTDz[YNz\XSrb36gZY5lKHB4NTDlfJBz\XO\|aX;uJIxmfmWucx?=	MlG5NlE4ODlzM{C=
LAPC-4	MVjGeY5kfGmxbjDhd5NigQ>?	MWCyNEDPxE1?	MXvEUXNQ	M{n6OIRm[3KnYYPld{BRW0Fic3XjdoV1cW:wIHHu[EBxPjViZYjwdoV{e2mxbjDs[ZZmdHN?	MnjENlE4ODlzM{C=
Kasumi-1	NYTiS4J5T3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	M{Lmfp42OCEQvF2=	NEH3OoNFVVOR	MmrIbY5pcWKrdIOgZ4VtdCCycn;sbYZmemG2aX;u	MUSyN\|M6ODV\|Nh?=
SKNO-1	M1jTbWdzd3e2aDDpcohq[mm2b4L5JIF{e2G7	M13GNJ42OCEQvF2=	MYrEUXNQ	M2j3cIlvcGmkaYTzJINmdGxicILvcIln\XKjdHnvci=>	M1z1cFI{OzlyNUO2
Kasumi-1	Mn;5T4lv[XOnIHHzd4F6	NHjEbXh,OTBizszN	MnXkSG1UVw>?	MmjTdoVlfWOnczDlfJBz\XO\|aX;uJI9nKGGlZYT5cIF1\WRiaHnzeI9v\SCKMz\|CpIMuc2m2wrDhcoTDqGKlbD2y	MXWyN\|M6ODV\|Nh?=
SKNO-1	NVLOdZBTU2mwYYPlJIF{e2G7	NWG4dHlwhjFyIN88US=>	NYDYSoZCTE2VTx?=	M3XZU5Jm\HWlZYOg[ZhxemW\|c3nvckBw\iCjY3X0fYxifGWmIHjpd5RwdmViSEOsxsBkNWurdNMgZY5lyqCkY3ytNi=>	NGHVNFYzOzN7MEWzOi=>
A549	MX\GeY5kfGmxbjDhd5NigQ>?	NX7Qd5ZsOTBizszN	NXLVPW9LTE2VTx?=	M4j4doVvcGGwY3XzJI1qfG:2aXOgZ4F1[XO2cn;wbIU>	MYmyOFc1PjV5NB?=
NRK-52E	NWXyflM2TnWwY4Tpc44h[XO\|YYm=	M1GxVVExKM7:TR?=	MYnEUXNQ	MkfGbY5pcWKrdIOgRY5oKEmLLXnu[JVk\WRiU2TBWFMhdnWlbHXhdkB1emGwc3zvZ4F1cW:wIHHu[EB1cGViZYjwdoV{e2mxbjDv[kBVT0ZvzsKxMEBkd2yuYXflckBKXiCjbnSg[oljem:wZXP0bY4>	MlPONlUxQDhyMEK=
PC12	NVHTd3c2T3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	MknNglEzNjVizszN	M1;tcmROW09?	NF3hc3pxemW4ZX70d{BVW0FvaX7keYNm\CCwZYXybZRmKG[xcn3heIlwdg>?	M{m3d\|I2OTJ6M{i2
HPMCs	M{f2NWZ2dmO2aX;uJIF{e2G7			MWPy[ZZmenOnczDldIl1cGWuaXHsJJRwKG2nc3XuZ4h6dWGuIITyZY5{cXSrb36gc4YhcHWvYX6gdIVzcXSxbnXhcEBu\XOxdHjlcIlidCClZXzsdy=>	NHnMPZMzPjB2NUe4NC=>
A549	M1jKPWZ2dmO2aX;uJIF{e2G7	NHnKe\|J,PTBizszN	MXfEUXNQ	NFzw[Ypi\m[nY4TzJJRp\SC4aYLhcEBtcW[nIHP5Z4xmKGGwZDDoc5N1KHKnc4DvcpNm	M4fIS\|I3PzFzN{S4
RAW264.7	NX:yWoc1TnWwY4Tpc44h[XO\|YYm=	NFz1Wop,OzBizszN	M1XVWWROW09?	MXzy[YR2[2W\|IIDyc{1qdm[uYX3tZZRwenliZ3Xu[UBmgHC{ZYPzbY9v	M1fKSVI3PzF6NUi2
MEMM	NX7XU\|ZxU2mwYYPlJIF{e2G7	MnvoNVUhyrWP	M1jRXGROW09?	MlW5[IVkemWjc3XzJIFk\XS7bHH0bY9vKG:oIHjpd5RwdmViSEO=	MViyOlkzOTVyNh?=
MEMM	MXvHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?	MYL+NlAhyrWP	MUfEUXNQ	NIDBWJlqdmirYnn0d{Bk\WyuIIDyc4xq\mW{YYTpc44>	NV23WWtkOjZ7MkG1NFY>
MEMM	NULtfoZzSXCxcITvd4l{KGG\|c3H5	M2TUeVE2KML3TR?=	Mn74SG1UVw>?	NV;4d5JycW6mdXPld{B1cGVicILld4Vv[2Vib3[geIhmKGGyb4D0c5NqeyCycn;0[YlvNCClbHXheoVlKEOjc4Dhd4UuOw>?	M2r3d\|I3QTJzNUC2
T47D	NHX4OFRIem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	NGLBVocyOCEQvF2=	NGG5eopFVVOR	M2XFd2lEPTB;N{Kgcm0>	M2K0dVE5OzhzNES0
ZR-75-1	M{PjfWdzd3e2aDDpcohq[mm2b4L5JIF{e2G7	Ml3RNVAh\|ryP	M2fUOGROW09?	NF[xVHpKSzVyPUe5JI5O	M36zRVE5OzhzNES0
BT474	M{\Lcmdzd3e2aDDpcohq[mm2b4L5JIF{e2G7	MVyxNEDPxE1?	NHHOXnVFVVOR	M3rBSGlEPTB;OE[gcm0>	NWjTOJRNOTh\|OEG0OFQ>
HCC1954	M3rLW2dzd3e2aDDpcohq[mm2b4L5JIF{e2G7	NVv6U3M5OTBizszN	M4r6WmROW09?	NFjaXIpKSzVyPUGxPUBvVQ>?	M1zXXlE5OzhzNES0
MDA-MB-453	M4KyTWdzd3e2aDDpcohq[mm2b4L5JIF{e2G7	MWixNEDPxE1?	NFLoNWFFVVOR	MnnpTWM2OD17N{Wgcm0>	NFy1PJAyQDN6MUS0OC=>
MDA-MB-468	Mo\3S5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	NITDT20yOCEQvF2=	M{LvT2ROW09?	Mlf0TWM2OD1\|MkC4JI5O	MmTKNVg{QDF2NES=
SkBr3	NHHDdHRIem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	M1m2VlExKM7:TR?=	NVHl[FJCTE2VTx?=	MXXJR\|UxRjFyLECwNEBvVQ>?	MnSwNVg{QDF2NES=
MDA-MB-231	MVzHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?	NEnzT\|IyOCEQvF2=	M{PJ[GROW09?	MkXtTWM2OD5zMDywNFAhdk1?	NVnzZlVDOTh\|OEG0OFQ>
HCT116	NXPIOXNxT3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	Mn[1NVAh\|ryP	Mn;kSG1UVw>?	MWrJR\|UxRTV6M{[gcm0>	MWqxPFM5OTR2NB?=
HT29	MWnHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?	M1jzOFExKM7:TR?=	NYPnRlJbTE2VTx?=	MXnJR\|UxRjFyLECwNEBvVQ>?	NVi4RoxSOTh\|OEG0OFQ>
HFF	NW\IPI9iT3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	NXfkfnhFOTBizszN	MYrEUXNQ	NUTpRXFuUUN3ME23OlE2KG6P	NYTXbnJGOTh\|OEG0OFQ>
HN5	M{TXR2dzd3e2aDDpcohq[mm2b4L5JIF{e2G7	NIfHRncyOCEQvF2=	MYTEUXNQ	NV:3cY9NUUN3ME6xNEwxODBibl2=	MlPWNVg{QDF2NES=
786-0	M3zRc2dzd3e2aDDpcohq[mm2b4L5JIF{e2G7	M3PhTFExKM7:TR?=	MYLEUXNQ	NH7tV2VKSzVyPUSwNFkhdk1?	M375T\|E5OzhzNES0
H157	NGjRbGJIem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	M3\rW\|ExKM7:TR?=	NGf6[lBFVVOR	M{fwb2lEPTB;Mk[0NkBvVQ>?	MoT1NVg{QDF2NES=
NCI-H460	NIDMO\|dIem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	M4HZNFExKM7:TR?=	MonQSG1UVw>?	MkPKTWM2OD5{LEWwNEBvVQ>?	NHv3UJEyQDN6MUS0OC=>
SKOV-3	MXzHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?	NVTTcWdtOTBizszN	Mn7qSG1UVw>?	NF[xXHpKSzVyPUKxNlYhdk1?	M2PVd\|E5OzhzNES0
OVCAR-3	Mn:zS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	MlvFNVAh\|ryP	Mnu2SG1UVw>?	M1jLfWlEPTB;MkmxPEBvVQ>?	MX2xPFM5OTR2NB?=
BXPC3	MkDvS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	NILsRmkyOCEQvF2=	NEizO3JFVVOR	Mm\GTWM2OD1\|MUSxJI5O	MoGzNVg{QDF2NES=
MiaPaCa	MkLJS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	M2PRd\|ExKM7:TR?=	NIPtcZNFVVOR	MVjJR\|UxRTV2M{Ogcm0>	NUfCfZZPOTh\|OEG0OFQ>
PANC-1	NHPkRo1Iem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	MlTJNVAh\|ryP	Moq1SG1UVw>?	NGDuUI5KSzVyPUi2PFEhdk1?	NHfnd5UyQDN6MUS0OC=>
LNCaP	NVKz[2duT3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	MX[xNEDPxE1?	MYXEUXNQ	M1\RcmlEPTB;MUS3JI5O	M4T4O\|E5OzhzNES0
DU145	NHvxXWdIem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	NWnPNllqOTBizszN	NV;pXI1QTE2VTx?=	M3rrO2lEPTB;M{ixNkBvVQ>?	NIfsTIwyQDN6MUS0OC=>
PC3	M3WzbGdzd3e2aDDpcohq[mm2b4L5JIF{e2G7	MXixNEDPxE1?	M1K1fWROW09?	NHmwOphKSzVyPkGwMFAxOCCwTR?=	NYq1eXZ3OTh\|OEG0OFQ>
BT474	NWS4XVl6U2mwYYPlJIF{e2G7	NX7KNZIxOTBizszN	M1LyeGROW09?	MV\pcohq[mm2czDwS3NMO87{IIfpeIghUUN3MDDv[kAyPjBibl2=	MmPMNVg{QDF2NES=
786-0	MXXLbY5ie2ViYYPzZZk>	NXPUbWpzOTBizszN	NXzt[XFXTE2VTx?=	NIXGOI9qdmirYnn0d{BxT1ONM98yJJdqfGhiSVO1NEBw\iBzNUCgcm0>	NXrKU5pSOTh\|OEG0OFQ>
LNCaP	Ml\HT4lv[XOnIHHzd4F6	M{PTPVExKM7:TR?=	M1j3bGROW09?	M1vYWYlvcGmkaYTzJJBIW0t\|zsKge4l1cCCLQ{WwJI9nKDR\|IH7N	M1[2V\|E5OzhzNES0
PC3	MVTLbY5ie2ViYYPzZZk>	NYTDNINmOTBizszN	M3nQT2ROW09?	NGfBVW5qdmirYnn0d{BxT1ONM98yJJdqfGhiSVO1NEBw\iB2OTDuUS=>	NXHtW4o3OTh\|OEG0OFQ>
KARPAS-231	NYCzfWNpT3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	NFLXOXYyOCEQvF2=	M2\lb2ROW09?	M{nwR2VEPTB;NEGgcm0>	NXLETWhkOTlyNkS3N\|A>
CCRFSB	MonBS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	NELWXI4yOCEQvF2=	NWLqeGEzTE2VTx?=	NF\Xc5VGSzVyPUG1OUBvVQ>?	Ml:5NVkxPjR5M{C=
SUP B15	MVXHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?	NU\0N2lYOTBizszN	M3XKfmROW09?	MWXFR\|UxRTF7NzDuUS=>	MV[xPVA3PDd\|MB?=
SD-1	MX7Hdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?	NVvqO5RqOTBizszN	NV3NO\|FYTE2VTx?=	M2PEcmVEPTB;M{KwJI5O	MnLCNVkxPjR5M{C=
RS4;11	M1XtZ2dzd3e2aDDpcohq[mm2b4L5JIF{e2G7	NUHIZYs5OTBizszN	NX;MWHFjTE2VTx?=	MUPFR\|UxRTZ3NDDuUS=>	NFrm[4MyQTB4NEezNC=>
MN-60	NFO0XnRIem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	M2nyb\|ExKM7:TR?=	NUnRVI5mTE2VTx?=	MmjaSWM2OD1\|NkCyJI5O	NEmwdVIyQTB4NEezNC=>
Tanoue	Ml;ES5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	MYqxNEDPxE1?	NFTPVIhFVVOR	M1\qcmVEPTB;NEWxO{BvVQ>?	MVWxPVA3PDd\|MB?=
RCH-ACV	NY\iendjT3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	NWnUU49pOTBizszN	NH7SNYVFVVOR	MV3FR\|UxRTF3MjDuUS=>	MnWxNVkxPjR5M{C=
SEM	NFqzfIpIem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	NX3y[YpOOTBizszN	MWfEUXNQ	M4K5dWVEPTB;MkCyJI5O	MUixPVA3PDd\|MB?=
KASUMI-2	M1;3eGdzd3e2aDDpcohq[mm2b4L5JIF{e2G7	MW[xNEDPxE1?	NE\q[WlFVVOR	Mnn0SWM2OD1{MkWgcm0>	NUP5[WM3OTlyNkS3N\|A>
REH	NInJTlhIem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	M3yybVExKM7:TR?=	NHf6PY1FVVOR	NGPGSllGSzVyPUK4PEBvVQ>?	M2fvXlE6ODZ2N{Ow
697	MkDZS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	M4POdFExKM7:TR?=	Mn35SG1UVw>?	M1LS[mVEPTB;M{O4JI5O	MVmxPVA3PDd\|MB?=
NALM-6	MUHHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?	M1P6O\|ExKM7:TR?=	MXnEUXNQ	Mm\TSWM2OD12MkGgcm0>	NEnlOHAyQTB4NEezNC=>
MHH-CALL–3	NEXFT4lIem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	MnLVNVAh\|ryP	MUPEUXNQ	MXrFR\|UxRThzMjDuUS=>	MnzjNVkxPjR5M{C=
MHH-CALL–2	MlfFS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	MoHUNVAh\|ryP	MV;EUXNQ	M1PmOmVEPTB;MkGxOEBvVQ>?	M{[5OFE6ODZ2N{Ow
J.GAMMA-1	NWC2blA3T3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	MmraNVAh\|ryP	MVXEUXNQ	M3PqNmVEPTB;NkWgcm0>	M4XITlE6ODZ2N{Ow
JR45.01	MkfBS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	MYexNEDPxE1?	NXu5Tll7TE2VTx?=	NHf1ZZRGSzVyPU[4JI5O	NXHxOo9ZOTlyNkS3N\|A>
A3	NHPsRYpIem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	NF[0S2UyOCEQvF2=	MWXEUXNQ	MojVSWM2OD14OTDuUS=>	NX\Z[oNYOTlyNkS3N\|A>
I 2.1	NYTxUlNOT3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	M4PyUlExKM7:TR?=	MoSzSG1UVw>?	M1ixSGVEPTB;N{Ogcm0>	NHO5VIoyQTB4NEezNC=>
MOLT-3	MXLHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?	M1XQflExKM7:TR?=	NHTscVFFVVOR	MmHYSWM2OD15NDDuUS=>	MoP2NVkxPjR5M{C=
P116	M3rTfWdzd3e2aDDpcohq[mm2b4L5JIF{e2G7	MXKxNEDPxE1?	NIjiW4xFVVOR	MYfFR\|UxRTd6IH7N	NIXUWFkyQTB4NEezNC=>
J.Cam1.6	MkD1S5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	NYTPVm81OTBizszN	NIrzUpFFVVOR	NVr1XFNNTUN3ME23PUBvVQ>?	MkTqNVkxPjR5M{C=
I 9.2	MnjHS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	MnruNVAh\|ryP	MXvEUXNQ	M4qx[mVEPTB;OECgcm0>	MV[xPVA3PDd\|MB?=
LOUCY	MXHHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?	NV30ZYM4OTBizszN	MXjEUXNQ	MmTNSWM2OD1zMUegcm0>	NYnYOYRJOTlyNkS3N\|A>
J.RT3-T3.5	MXfHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?	MYKxNEDPxE1?	NIHGc\|lFVVOR	MlXwSWM2OD1zMkOgcm0>	NXTWNoY6OTlyNkS3N\|A>
800000	NELQVJhIem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	NULBdWZMOTBizszN	MmLlSG1UVw>?	NH3V[XNGSzVyPUG2N{BvVQ>?	NEH6cHcyQTB4NEezNC=>
Jurkat	NUHGco5GT3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	NFP0WWEyOCEQvF2=	MX7EUXNQ	MX;FR\|UxRTJ{NTDuUS=>	NWjWPWRVOTlyNkS3N\|A>
MOLT-4	NXX6OIl[T3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	MonpNVAh\|ryP	MlrySG1UVw>?	NXX0U3pyTUN3ME2yN\|Ihdk1?	Mn7CNVkxPjR5M{C=
Molt-16	M3LWPWdzd3e2aDDpcohq[mm2b4L5JIF{e2G7	Ml3RNVAh\|ryP	M3nGOWROW09?	MoXXSWM2OD1{NEGgcm0>	NGficnAyQTB4NEezNC=>
CEM/C3	NIjvZndIem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	M{exO\|ExKM7:TR?=	NFLVVWpFVVOR	NFjNfZlGSzVyPUK1O{BvVQ>?	MmrTNVkxPjR5M{C=
CEM/C2	MnvmS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	NFTPbpUyOCEQvF2=	MYDEUXNQ	NX7jXZZ1TUN3ME2yO\|Ehdk1?	NYDsOXlsOTlyNkS3N\|A>
CCRFCEM	NXHpelN7T3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	NELqcIMyOCEQvF2=	NW[5TII5TE2VTx?=	NXvwW2N2TUN3ME2zNlchdk1?	MX[xPVA3PDd\|MB?=
CEM/C1	MYfHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?	MWmxNEDPxE1?	M2LnfmROW09?	NWHaemdjTUN3ME2zPFIhdk1?	MXixPVA3PDd\|MB?=
SUPTI[VB]	M4PhV2dzd3e2aDDpcohq[mm2b4L5JIF{e2G7	NF7YZZgyOCEQvF2=	NW\GOYJCTE2VTx?=	NH3xVohGSzVyPU[xPUBvVQ>?	NXPJUHVzOTlyNkS3N\|A>
CCRF–HSB-2	M{HEfmdzd3e2aDDpcohq[mm2b4L5JIF{e2G7	M{S1[\|ExKM7:TR?=	NXXn[G5nTE2VTx?=	M122W2VEPTB;MkGxO{BvVQ>?	MV6xPVA3PDd\|MB?=
I 2.1	MUDBdI9xfG:\|aYOgZZN{[Xl?	MXyxNEDPxE1?	Ml;aSG1UVw>?	M{jITIlv\HWlZYOgZZBweHSxc3nz	MkX3NVkxPjR5M{C=
I 9.2	NELvPHZCeG:ydH;zbZMh[XO\|YYm=	NYDOT3l3OTBizszN	NUm4O5pXTE2VTx?=	M1HTdYlv\HWlZYOgZZBweHSxc3nz	M1npbVE6ODZ2N{Ow
A3	MkHaRZBweHSxc3nzJIF{e2G7	NUTCUYVNOTBizszN	Mke5SG1UVw>?	MWLpcoR2[2W\|IHHwc5B1d3Orcx?=	M1vzclE6ODZ2N{Ow
RD	MWrHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?	MXixNEDPxE1?		NX;x[Zo1UUN3ME6xNEDPxE1?	MWCyNFc1ODZ{Mx?=
Rh41	M2izZ2dzd3e2aDDpcohq[mm2b4L5JIF{e2G7	M2jmUFExKM7:TR?=		NEnO[3JKSzVyPUOzMlghdk1?	NWLhWFZROjB5NEC2NlM>
Rh18	NIDzVYxIem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	Moi5NVAh\|ryP		MUnJR\|UxRTNyMzDuUS=>	MVmyNFc1ODZ{Mx?=
Rh30	M{D3b2dzd3e2aDDpcohq[mm2b4L5JIF{e2G7	NG\VcJMyOCEQvF2=		M1WwbmlEPTB;ND64NUDPxE1?	M33LW\|IxPzRyNkKz
BT-12	MlLvS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	MWCxNEDPxE1?		M4K0UWlEPTB-MUCg{txO	M1S3TlIxPzRyNkKz
CHLA-266	NG\xfHFIem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	Mn[4NVAh\|ryP		MUnJR\|UxRTFwMkKg{txO	MWGyNFc1ODZ{Mx?=
TC-71	NGf6TI9Iem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	NI\J[WIyOCEQvF2=		MY\JR\|UxRTJwNUKg{txO	Mm\tNlA4PDB4MkO=
CHLA-9	MkLvS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	NHT4UJMyOCEQvF2=		NUjZS2I1UUN3ME21PVEhdk1?	NHLqUYQzODd2ME[yNy=>
CHLA-10	MoOwS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	MVixNEDPxE1?		MkDETWM2OD1zMEKgcm0>	MkXMNlA4PDB4MkO=
CHLA-258	MX7Hdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?	NYnZcnF5OTBizszN		M4HoN2lEPTB;MT6wOUDPxE1?	NYTkSYE5OjB5NEC2NlM>
GBM2	NEnGUHRIem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	MXmxNEDPxE1?		MWjJR\|UxRTlwMUWg{txO	M3XHUVIxPzRyNkKz
NB-1643	MVnHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?	NYO1T5N2OTBizszN		NU\uclQ3UUN3ME21MlQh\|ryP	NEHBb\|kzODd2ME[yNy=>
NB-Ebc1	M13oZ2dzd3e2aDDpcohq[mm2b4L5JIF{e2G7	MYWxNEDPxE1?		MVPJR\|UxRjFyIN88US=>	NYDMUIVyOjB5NEC2NlM>
CHLA-90	NF;JR3RIem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	MlvVNVAh\|ryP		MkjSTWM2OD5zMDFOwG0>	MYmyNFc1ODZ{Mx?=
CHLA-136	NYfESXdVT3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	NVXrbot2OTBizszN		NIXkfINKSzVyPkGwJO69VQ>?	NULXS49WOjB5NEC2NlM>
NALM-6	M13nUmdzd3e2aDDpcohq[mm2b4L5JIF{e2G7	MX6xNEDPxE1?		NHLkXY1KSzVyPUK2OUBvVQ>?	NUjROIsxOjB5NEC2NlM>
COG-LL-317	MYTHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?	NHrMdWoyOCEQvF2=		NXnLeo5LUUN3ME22MlQ6KG6P	MX[yNFc1ODZ{Mx?=
RS4;11	MVrHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?	M3HhU\|ExKM7:TR?=		NELX[VlKSzVyPUG0O{BvVQ>?	NEXEdmczODd2ME[yNy=>
MOLT-4	NG[3clBIem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	MUixNEDPxE1?		NFjSVm9KSzVyPUSwJI5O	NHfp[GozODd2ME[yNy=>
CCRF-CEM	M4jQN2dzd3e2aDDpcohq[mm2b4L5JIF{e2G7	NIn2PIYyOCEQvF2=		MmrsTWM2OD1{Nkigcm0>	MV:yNFc1ODZ{Mx?=
Kasumi-1	NWDac\|N2T3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	MofBNVAh\|ryP		M1X1O2lEPTB;MUC3JI5O	MUCyNFc1ODZ{Mx?=
Karpas-299	Mnm5S5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	M4\keFExKM7:TR?=		M3LSXGlEPTB;Mj65N{DPxE1?	MlfoNlA4PDB4MkO=
Ramos-RA1	M4P2N2dzd3e2aDDpcohq[mm2b4L5JIF{e2G7	NHXxXG8yOCEQvF2=		NYKxUmFXUUN3ME23MlM2KM7:TR?=	NV75c\|ZQOjB5NEC2NlM>
H1299	M2PtZWtqdmG\|ZTDhd5NigQ>?	M2S0SlExKM7:TR?=		NFnTRlhqdmirYnn0d{BKU0KNRT3pcoR2[2WmIFHreEBC[3SrdnH0bY9v	NELLSWYzOTlyOE[xOi=>

Click to View More Cell Line Experimental Data

Assay

Methods	Test Index	PMID

Western blot	cMET / p-cMET / p-AKT / p-ERK / p-rpS6	23022995
Growth inhibition assay	Cell viability	23598276

In vivo

All three xenograft models treated with ARQ-197 display reductions in tumor growth: 66% in the HT29 model, 45% in the MKN-45 model, and 79% in the MDA-MB-231 model. In these xenograft studies, no significant body weight changes following oral administration of ARQ-197 at 200 mg/kg are observed. Pharmacodynamically, the phosphorylation of c-Met in human colon xenograft tumors (HT29) is strongly inhibited by ARQ-197, as assessed by a dramatic reduction of c-Met autophosphorylation 24 hours after a single oral dose of 200 mg/kg of ARQ-197. This same dosage in mice exhibits that tumor xenografts are exposed to sustained plasma levels of ARQ-197, consistent with the observed pharmacodynamic inhibition of c-Met phosphorylation and inhibition of proliferation of c-Met harboring cancer cell lines. Plasma levels of ARQ-197 10 hours after dosing are determined to be 1.3 μM, more than 3-fold above the biochemical inhibitory constant of ARQ-197 for c-Met. Therefore, ARQ-197 is able to suppress its target in vivo in the xenografted human tumor tissue. In conclusion, ARQ-197 inhibits the growth of c-Met-dependent xenografted human tumors.^[1]

Protocol (from reference)

Kinase Assay:^[1]	c-Met SDS-PAGE in vitro kinase assay: Recombinant c-Met protein (100 ng) is preincubated with increasing concentrations of ARQ-197 for 30 minutes at room temperature. Following preincubation, 100 μM of poly-Glu-Tyr substrate and various concentrations of ATP containing 5 μCi of [γ-32P]ATP are added to the reaction mixture. The reaction is incubated for 5 minutes at room temperature and then stopped by the addition of 5 μL of SDS-polyacrylamide gel, reducing sample buffer. The samples are then loaded onto a 7.5% acrylamide gel and SDS-PAGE is performed. The phosphorylated poly-Glu-Tyr substrates are ultimately visualized by autoradiography. c-Met activity is quantified by densitometry.
Cell Research:^[1]	Cell lines: T29, MKN-45 and MDA-MB-231 cells Concentrations: 0.03-10 μM Incubation Time: 24, 32, and 48 hours Method: HT29, MKN-45, and MDA-MB-231 cells are seeded in black 96-well plates at 5 × 10³ cells per well overnight in a medium with 10% FBS. The next day, cells are treated with increasing concentrations of ARQ-197 (0.03-10 μM) for 24, 32, and 48 hours at 37 °C. After ARQ-197 treatment, the drug-containing medium is removed and cells are incubated for at least 10 minutes in a labeling solution (10 mM HEPES, 140 mM NaCl, and 6 mM CaCl₂) containing 2 μg/mL Hoescht 33342 (blue channel), 500-times diluted Annexin V-FITC (green channel), and 1 μg/mL propidium iodide (red channel). High-content image acquisition and analysis are carried out. The program is set to take four images per well. The exposure time is set at 16.7 ms/10% gain, 500 ms/35% gain, and 300 ms/30% gain for the 4,6-diamidino-2-phenylindole, FITC, and rhodamine channels, respectively. Images are processed and the numbers of positive cells for each channel and each condition are determined. In addition, HT29 cells are treated with increasing concentrations of ARQ-197 for 32 hours in the absence or the presence of 25, 50, and 100 μM ZvAD-FMK (irreversible general caspase inhibitor), and the same procedures are undertaken. All experiments are done in triplicate. To determine whether the apoptotic effect is due to c-Met inhibition, the effect of ARQ-197 when glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and c-Met are knocked down using siRNA is investigated. HT29, MKN-45, and MDA-MB-231 cells are transfected with a nontargeted control siRNA, a gapgh-targeted control siRNA, or a met-targeted siRNA. After 3 days, c-Met, GAPDH, and β-actin expression levels are determined using specific antibodies. To determine if the effect is caspase dependent, HT29, MKN-45, and MDA-MB-231 cells are transfected with a met-targeted siRNA for 2 days and incubated in the absence or the presence of increasing concentrations of ZvAD-FMK for 1 additional day. A nontargeted siRNA and a gapgh-targeted siRNA (siRNA GAPDH) are also transfected in parallel, as controls. Cells are then stained with Annexin V-FITC and propidium iodide, and the percentage of apoptotic cells is determined.
Animal Research:^[1]	Animal Models: Female athymic nude mice bearing HT29, MKN-45, or MDA-MB-231 tumor xenografts Dosages: 200 mg/kg Administration: Orally administered

References

Solubility (25°C)

In vitro

Chemical Information

Molecular Weight	369.42
Formula	C₂₃H₁₉N₃O₂
CAS No.	905854-02-6
Storage	3 years	-20°C	powder
Storage	2 years	-80°C	in solvent
Smiles	C1CC2=C3C(=CC=C2)C(=CN3C1)C4C(C(=O)NC4=O)C5=CNC6=CC=CC=C65

Download Tivantinib (ARQ 197) SDF

In vivo Formulation Calculator (Clear solution)

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Clinical Trial Information

NCT Number	Recruitment	Interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT02150733	Completed	Drug: Tivantinib	Hepatic Impairment\|Solid Tumor\|Cancer	Daiichi Sankyo Inc.\|Medpace Inc.	April 2014	Phase 1
NCT01892527	Unknown status	Drug: Tivantinib (ARQ197)	Colorectal Cancer Metastatic\|C-met Overexpression	Armando Santoro MD\|Istituto Clinico Humanitas	March 2013	Phase 2
NCT02049060	Completed	Drug: Tivantinib	Malignant Pleural Mesothelioma\|Nonsquamous Nonsmall Cell Neoplasm of Lung	Armando Santoro MD\|Istituto Clinico Humanitas	January 2013	Phase 1\|Phase 2
NCT01755767	Completed	Drug: Tivantinib\|Drug: Placebo	Hepatocellular Carcinoma	Daiichi Sankyo Inc.\|ArQule Inc. (a wholly owned subsidiary of Merck Sharp and Dohme a subsidiary of Merck & Co. Inc.)	December 27 2012	Phase 3

(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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Frequently Asked Questions

Question 1:
Are there any other solutions (apart from DMSO) I can dissolve S2753 for in vivo experiment?

Answer:
S2753 Tivantinib (ARQ 197) can be dissolved in 1% methylcellulose at15 mg/ml as a suspension.

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