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Tivantinib (ARQ 197)

Name: Tivantinib (ARQ 197)
Brand: Selleck Chemicals
SKU: S2753
Rating: 5 (37 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 37 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	M2XnTGtqdmG\|ZTDhd5NigQ>?	NYXXc4FjhjFyIN88US=>		MnnmbY5pcWKrdIOgZ{1O\XRicHjvd5Bpd3K7bHH0bY9vKGGwZDDkc5dve3S{ZXHtJIMuVWW2IIPp[45idGmwZzDwZZRpf2G7cx?=	M3HJO\|IxPDh2MEG4
HT29	MnnlT4lv[XOnIHHzd4F6	NFqyco1,OTBizszN		NXTMfZJJcW6qaXLpeJMh[y2PZYSgdIhwe3Cqb4L5cIF1cW:wIHHu[EBld3ewc4Ty[YFuKGNvTXX0JJNq\26jbHnu[{Bx[XSqd3H5dy=>	MnXxNlA1QDRyMUi=
MDA-MB-231	MYfLbY5ie2ViYYPzZZk>	MoDGglExKM7:TR?=		MmjvbY5pcWKrdIOgZ{1O\XRicHjvd5Bpd3K7bHH0bY9vKGGwZDDkc5dve3S{ZXHtJIMuVWW2IIPp[45idGmwZzDwZZRpf2G7cx?=	MUCyNFQ5PDBzOB?=
NCI-H441	NGLCSpJMcW6jc3WgZZN{[Xl?	M{\CVZ4yOCEQvF2=		M4ftUIlvcGmkaYTzJIMuVWW2IIDoc5NxcG:{eXzheIlwdiCjbnSg[I94dnO2cnXhcUBkNU2ndDDzbYdv[WyrbnegdIF1cHejeYO=	NUTiZ\|lNOjB2OESwNVg>
SK-MEL-28	NEm5fVdIem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	MVSzN{DPxE1?		MmKyTWM2OD5\|MzFOwG0>	MorFNlA1QDRyMUi=
NCI-H661	NX7jU5ZsT3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	NFzMcmQ{OyEQvF2=		NUX5THoyUUN3ME6zN{DPxE1?	MmrONlA1QDRyMUi=
NCI-H446	MnK1S5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	NFfse4Q{OyEQvF2=		NVrpbFlkUUN3ME23JO69VQ>?	NGCwOWkzODR6NECxPC=>
MDA-MB-231	M33xUWdzd3e2aDDpcohq[mm2b4L5JIF{e2G7	M3;NTFM{KM7:TR?=		NY\FTVJMUUN3ME2wMlU2KM7:TR?=	MUSyNFQ5PDBzOB?=
DLD-1	NWeydXR6T3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	M3TTVlM{KM7:TR?=		MoLTTWM2OD1yLkWzJO69VQ>?	MoqyNlA1QDRyMUi=
A549	M4HBfmdzd3e2aDDpcohq[mm2b4L5JIF{e2G7	NHjaUYs{OyEQvF2=		MUjJR\|UxRTBwNUmg{txO	MVOyNFQ5PDBzOB?=
SK-OV-3	M3\6[mdzd3e2aDDpcohq[mm2b4L5JIF{e2G7	MnzLN\|Mh\|ryP		NEi2ZpFKSzVyPUCuOlYh\|ryP	NVjIR3lJOjB2OESwNVg>
NCI-H460	MlXCS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	NVPWWlVqOzNizszN		NIDYU2xKSzVyPUCuOkDPxE1?	NILt[44zODR6NECxPC=>
A375	NHnZdFdIem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	MY[zN{DPxE1?		NHy5SYJKSzVyPUCuOFIh\|ryP	NF3zRo8zODR6NECxPC=>
NCI-H441	NXjLclI6T3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	MmPLN\|Mh\|ryP		MX7JR\|UxRTBwMzFOwG0>	Mlz4NlA1QDRyMUi=
HT29	MoTLS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	NIjudXQ{OyEQvF2=		MkPGTWM2OD1yLkS5JO69VQ>?	NV7lWIdvOjB2OESwNVg>
MKN-45	MWjHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?	MXWzN{DPxE1?		NXm3OpBCUUN3ME2wMlU5KM7:TR?=	MX6yNFQ5PDBzOB?=
HT29	MYrBdI9xfG:\|aYOgZZN{[Xl?	MmXNglExKM7:TR?=		NYj6b3B1e2mpbnnmbYNidnSueTDpcoR2[2W\|IHHwc5B1d3OrczDifUA5OC17MDWu	MlW5NlA1QDRyMUi=
MKN-45	NXixUopDSXCxcITvd4l{KGG\|c3H5	NUjRdHZrhjFyIN88US=>		NInrSmh{cWewaX\pZ4FvfGy7IHnu[JVk\XNiYYDvdJRwe2m\|IHL5JFgxNTlyJT6=	MoW1NlA1QDRyMUi=
MDA-MB-231	MnHkRZBweHSxc3nzJIF{e2G7	M2HEep4yOCEQvF2=		NYDJfHdOdW:mZYP0cJkhcW6mdXPld{BieG:ydH;zbZMh[nliM{WlMi=>	NIDxXmgzODR6NECxPC=>
MDA-MB-231/TGL	M2L1[Gdzd3e2aDDpcohq[mm2b4L5JIF{e2G7	MXf+NVAxKM7:TR?=		NYruV292T0l3ME2xMlIh\|ryP	NVnFVlVmOjJyMke2PVA>
1833/TGL	M4n0OWdzd3e2aDDpcohq[mm2b4L5JIF{e2G7	NUjhRXFshjFyMDFOwG0>		M1rnUGdKPTB;Mz63JO69VQ>?	MoPTNlIxOjd4OUC=
EBC1	MYDDfZRwfG:6aXRCpIF{e2G7	NELkS4x,OTBizszN		MU\pcohq[mm2czD0bIUh[2WubDDndo94fGhw	MkL1NlM2QTh{N{[=
SNU638	M4rBXmN6fG:2b4jpZ:Kh[XO\|YYm=	M2nVTZ4yOCEQvF2=		MYjpcohq[mm2czD0bIUh[2WubDDndo94fGhw	NWrmdZFzOjN3OUiyO\|Y>
A549	NEfwNY9EgXSxdH;4bYPDqGG\|c3H5	MorGglExKM7:TR?=		MWLuc5Qh[W[oZXP0	MlfzNlM2QTh{N{[=
H460	Mnf1R5l1d3SxeHnjxsBie3OjeR?=	NFPNd3N,OTBizszN		MkWwco91KGGoZnXjeC=>	NGewOmszOzV7OEK3Oi=>
HCC827	M1zpc2N6fG:2b4jpZ:Kh[XO\|YYm=	MUX+NVAh\|ryP		M3rvSo5wfCCjZn\lZ5Q>	NFSxXXkzOzV7OEK3Oi=>
A549	NGX5WZdHfW6ldHnvckBie3OjeR?=	M1r2cFExKM7:TR?=		M3fNWoRqe3K3cITzJI1q[3KxdIXieYxm	MoLLNlM2QTh{N{[=
EBC1	MkTqSpVv[3Srb36gZZN{[Xl?	MXuxNEDPxE1?		NEfoToZlcXO{dYD0d{BucWO{b4T1ZpVt\Q>?	M3m2XlI{PTl6Mke2
H460	NFzwcGhHfW6ldHnvckBie3OjeR?=	MXWxNEDPxE1?		NHjnd4JqdmirYnn0d{B1fWK3bHnuJJBwdHmvZYLpfoF1cW:w	M2\teVI2OzF\|MEGw
K562/VCR	NFm4XWlEgXSxdH;4bYPDqGG\|c3H5	M2XHR54yOCEQvF2=		MmXrd4hwf3NiY4n0c5RwgGmlIHHjeIl3cXS7	MkHiNlU{OTNyMUC=
CEM/VBL	M1fKfWN6fG:2b4jpZ:Kh[XO\|YYm=	NF7MRW5,OTBizszN		M2n6VJNpd3e\|IHP5eI91d3irYzDhZ5Rqfmm2eR?=	NVTrb\|lrOjV\|MUOwNVA>
U266	NIrMdVJEgXSxdH;4bYPDqGG\|c3H5	NILUWlB,OyEQvF5CpC=>		MWXJR\|UxRTFwMTFOwG0>	M1zTTlI2QDFyMEGz
OPM-2	Mn;UR5l1d3SxeHnjxsBie3OjeR?=	M{fV[J4{KM7:TdMg		NVPDeJNLUUN3ME2xMlgh\|ryP	M1[0PVI2QDFyMEGz
MM.1S	MXnDfZRwfG:6aXRCpIF{e2G7	M1vxO54{KM7:TdMg		M4nnWWlEPTB;MT62JO69VQ>?	MYqyOVgyODBzMx?=
MM.1R	NYnUe2VwT3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	MVizJO69VcLi		MVPpcohq[mm2czDj[YxtKGe{b4f0bEBjgSB2OTW=	NIfmcYozPThzMECxNy=>
RPMI-8226	Mn7nR5l1d3SxeHnjxsBie3OjeR?=	MV\+N{DPxE4EoB?=		M2HUb2lEPTB;MD65JO69VQ>?	NGrRcZkzPThzMECxNy=>
ANBL-6	NX7UVoxuS3m2b4TvfIlkyqCjc4PhfS=>	NGnJfVQyKM7:TdMg		NVm2bXBRcW6mdXPld{Bk\WyuIHTlZZRpKGK7IH3vdoUhfGijbjC1NEU>	M3rzXlI2QDFyMEGz
ANLB-6/V10R	MYLDfZRwfG:6aXRCpIF{e2G7	MofMNUDPxE4EoB?=		NVjpRodvcW6mdXPld{Bk\WyuIHTlZZRpKGK7IH3vdoUhfGijbjC1NEU>	MXSyOVgyODBzMx?=
KAS-6/1	M3nGWmN6fG:2b4jpZ:Kh[XO\|YYm=	M3:5[lEh\|ryPwrC=		NGjnSVNqdmS3Y3XzJINmdGxiZHXheIgh[nlibX;y[UB1cGGwIEWwKS=>	M{LtT\|I2QDFyMEGz
KAS-6/V10R	NVu5e5F1S3m2b4TvfIlkyqCjc4PhfS=>	MUixJO69VcLi		NF;uXmNqdmS3Y3XzJINmdGxiZHXheIgh[nlibX;y[UB1cGGwIEWwKS=>	M{jGTVI2QDFyMEGz
KAS-6/R10R	NHfTVXhEgXSxdH;4bYPDqGG\|c3H5	NFy4b4MyKM7:TdMg		M2P3bolv\HWlZYOgZ4VtdCCmZXH0bEBjgSCvb4LlJJRp[W5iNUCl	NGe5TG4zPThzMECxNy=>
8226/S	NH6zcHJIem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	NUjqUWZ1OyEQvF5CpC=>		NFnvPXZqdmirYnn0d{Bk\WyuIHfyc5d1cCCkeTC1OEU>	M4\rN\|I2QDFyMEGz
8226/LR-5	M13nb2dzd3e2aDDpcohq[mm2b4L5JIF{e2G7	MWGzJO69VcLi		Ml[zbY5pcWKrdIOgZ4VtdCCpcn;3eIgh[nliNUSl	MnHuNlU5OTByMUO=
Huh7	MXnDfZRwfG:6aXRCpIF{e2G7	M1;0PJ41NjhizszNxsA>	NU\rfo1iTE2VTx?=	NYHKSGs4UUN3ME25Mlkhdk1?	NYLr[nhrOjZ{NUmyOVA>
Hep3B	NHuzWJBEgXSxdH;4bYPDqGG\|c3H5	MonLglQvQCEQvF5CpC=>	MXTEUXNQ	NWT1SWdUUUN3ME20OFgvPyCwTR?=	NGn5bIEzPjJ3OUK1NC=>
HepG2	NY\6dVFuS3m2b4TvfIlkyqCjc4PhfS=>	MUH+OE45KM7:TdMg	NYrtOmQyTE2VTx?=	M2fFNWlEPTB;MUO5Mlc4KG6P	M{DtOlI3OjV7MkWw
Chang	NX;ldZVpS3m2b4TvfIlkyqCjc4PhfS=>	MXr+OE45KM7:TdMg	M1XhcGROW09?	MUnJR\|UxRTR2OD63JI5O	NVKyWGRiOjZ{NUmyOVA>
Huh7	NEj5eY1HfW6ldHnvckBie3OjeR?=	MUGxMlYh\|ryPwrC=	MWrEUXNQ	NH\ZfGJk[XW\|ZYOgZUBIOi:PIHPlcIwh[3mlbHWgZZJz\XO2	NFGzcXczPjJ3OUK1NC=>
Hep3B	NFT2cFZHfW6ldHnvckBie3OjeR?=	M3voXVEvPiEQvF5CpC=>	NUTq[lBmTE2VTx?=	MVHjZZV{\XNiYTDHNk9OKGOnbHygZ5lkdGViYYLy[ZN1	NH7rSHMzPjJ3OUK1NC=>
HepG2	NX:0V\|I{TnWwY4Tpc44h[XO\|YYm=	NXPmWZpoOS54IN88UeKh	M{TWTmROW09?	M{XrRYNifXOnczDhJGczN01iY3XscEBkgWOuZTDhdpJme3R?	M1jsb\|I3OjV7MkWw
Chang	MorPSpVv[3Srb36gZZN{[Xl?	MX2xMlYh\|ryPwrC=	M1nad2ROW09?	M{L5WYNifXOnczDhJGczN01iY3XscEBkgWOuZTDhdpJme3R?	MYCyOlI2QTJ3MB?=
MHCC97L	MoX0S5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	MkLkglExKM7:TR?=	NVXWUYFDTE2VTx?=	NHjYZVRKSzVyPUOxOUBvVQ>?	MYCyOlQ2QDl3Mx?=
MHCC97H	NXL4NYxTT3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	MWH+NVAh\|ryP	NHXMVVJFVVOR	NWLk[ol7UUN3ME2zOljjiIlibl2=	MkHONlY1PTh7NUO=
Huh7	MV;Hdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?	NIfDXW5,OTBizszN	MlLGSG1UVw>?	MmKxTWM2OD1{NkWgcm0>	MXyyOlQ2QDl3Mx?=
HepG2	NHTLfZRIem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	NIPLS4l,OTBizszN	NH72RnRFVVOR	NFvVU4lKSzVyPUO5NkBvVQ>?	MVGyOlQ2QDl3Mx?=
MHCC97L	MYXGeY5kfGmxbjDhd5NigQ>?	MWCxJO69VcLi	M1i0SGROW09?	MX7pcoR2[2W\|IH3pZ5JwfHWkdXzld{Bl\XCxbInt[ZJqgmG2aX;u	Mnf2NlY1PTh7NUO=
Huh7	MonYSpVv[3Srb36gZZN{[Xl?	MVOxJO69VcLi	NIX3UI9FVVOR	M4i1RYlv\HWlZYOgcYlkem:2dXL1cIV{KGSncH;sfY1memm8YYTpc44>	MYWyOlQ2QDl3Mx?=
MHCC97L	NUfhWGxbSXCxcITvd4l{KGG\|c3H5	MXOxJO69VcLi	MofDSG1UVw>?	MYHpcoR2[2W\|IHHwc5B1d3Orcx?=	MWqyOlQ2QDl3Mx?=
Huh7	MnjKRZBweHSxc3nzJIF{e2G7	MnzINUDPxE4EoB?=	NYHTUm92TE2VTx?=	MXvpcoR2[2W\|IHHwc5B1d3Orcx?=	Mn3qNlY1PTh7NUO=
C3H 10T1/2 mouse fibroblasts	MoHZT4lv[XOnIHHzd4F6	Mnv0NlUh\|ryP	NUHtOmFRTE2VTx?=	M3;3[JJm\HWlZYOgTIl{fG:wZTDIN{BidmRiSESgZYNmfHmuYYTpc44hdGW4ZXzzxsA>	M2XWdVIxPTN2M{S1
H23	NH\vOGZIem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	MkXBNlUh\|ryP	M3\0Z2ROW09?	MWHzbYdvcW[rY3HueIx6KGmwaHnibZR{KGOnbHyg[5Jwf3SqLh?=	NIPW[5czODV\|NEO0OS=>
WM35	MoL2S5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	MUCxNEDPxE1?	NWOzdlNLTE2VTx?=	NVjUb4M5e2mpbnnmbYNidnSueTDpcohq[mm2czDj[YxtKGe{b4f0bE4>	MXSyNFU{PDN2NR?=
NIH 3T3	NYXTdGI{T3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	MnfiNVAh\|ryP	NFnwZm9FVVOR	MnXN[I9meyCwb4SgbIF3\SCjIIPp[45q\mmlYX70JIlvcGmkaYTvdpkh\W[oZXP0	NEPZT5AzODV\|NEO0OS=>
H838	MVvHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?	NHHuUG4yOCEQvF2=	MXnEUXNQ	NX;B[VBY\G:nczDuc5QhcGG4ZTDhJJNq\26rZnnjZY51KGmwaHnibZRwenliZX\m[YN1	MYOyNFU{PDN2NR?=
H1395	NInQOVdIem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	MkPMNVAh\|ryP	MnW3SG1UVw>?	MXnkc4V{KG6xdDDoZZZmKGFic3nncolncWOjboSgbY5pcWKrdH;yfUBm\m[nY4S=	M2P3e\|IxPTN2M{S1
Quiescent S2	MoH6T4lv[XOnIHHzd4F6	M3;FeFMxKM7:TR?=	NWK2WXZYTE2VTx?=	MlrwZ49ueGyndHXsfUBi[nKxZ3H0[ZMhXFODLXnu[JVk\WRiaInw[ZJi[2W2eXzheIlwdiCxZjDIN2s1dWV\|IHjpd5RwdmW\|	MmDBNlE2OTh7MUW=
PC3	NXrVb29HSXCxcITvd4l{KGG\|c3H5	NGLXPFYzOCEQvF2=	MoDiSG1UVw>?	MXrpcoR2[2W\|IHHwc5B1d3Orcx?=	NYewT41LOjF5MEmxN\|A>
Du145	MmnvRZBweHSxc3nzJIF{e2G7	M3XNNVIxKM7:TR?=	NXTiZWxQTE2VTx?=	NF;XUpJqdmS3Y3XzJIFxd3C2b4Ppdy=>	NET2clkzOTdyOUGzNC=>
LNCaP	MUPBdI9xfG:\|aYOgZZN{[Xl?	MonlNlAh\|ryP	NVnQeVQyTE2VTx?=	MULpcoR2[2W\|IHHwc5B1d3Orcx?=	MUSyNVcxQTF\|MB?=
LAPC-4	Mm\wRZBweHSxc3nzJIF{e2G7	MYGyNEDPxE1?	MXPEUXNQ	NHHmVW9qdmS3Y3XzJIFxd3C2b4Ppdy=>	NGrkWIozOTdyOUGzNC=>
LNCaP	NFHPRWtHfW6ldHnvckBie3OjeR?=	M4DkWlIxKM7:TR?=	MmfXSG1UVw>?	NFG5O\|Fl\WO{ZXHz[ZMhWFODIIPlZ5JmfGmxbjDhcoQheDZ3IHX4dJJme3Orb36gcIV3\Wy\|	NELQ[mczOTdyOUGzNC=>
LAPC-4	MoroSpVv[3Srb36gZZN{[Xl?	Mo\aNlAh\|ryP	MWPEUXNQ	Mljw[IVkemWjc3XzJHBUSSC\|ZXPy[ZRqd25iYX7kJJA3PSCneIDy[ZN{cW:wIHzleoVtew>?	NFHUclkzOTdyOUGzNC=>
Kasumi-1	MoTCS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	NVG1UoplhjVyIN88US=>	MXLEUXNQ	NH;iSGtqdmirYnn0d{Bk\WyuIIDyc4xq\mW{YYTpc44>	MWKyN\|M6ODV\|Nh?=
SKNO-1	NVT0PXNwT3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	NX7Hd20yhjVyIN88US=>	MULEUXNQ	MWnpcohq[mm2czDj[YxtKHC{b3zp[oVz[XSrb36=	NEP0cowzOzN7MEWzOi=>
Kasumi-1	MXzLbY5ie2ViYYPzZZk>	NUj5fYczhjFyIN88US=>	M4raSWROW09?	NGrCU21z\WS3Y3XzJIV5eHKnc4Ppc44hd2ZiYXPleJlt[XSnZDDobZN1d26nIFizMOKh[y2taYVCpIFv\MLiYnPsMVI>	MoDuNlM{QTB3M{[=
SKNO-1	MmPBT4lv[XOnIHHzd4F6	MVL+NVAh\|ryP	MWfEUXNQ	M1zoTZJm\HWlZYOg[ZhxemW\|c3nvckBw\iCjY3X0fYxifGWmIHjpd5RwdmViSEOsxsBkNWurdNMgZY5lyqCkY3ytNi=>	MXOyN\|M6ODV\|Nh?=
A549	NWrTfG94TnWwY4Tpc44h[XO\|YYm=	M3LGPVExKM7:TR?=	MmHPSG1UVw>?	MnPt[Y5p[W6lZYOgcYl1d3SrYzDjZZRie3S{b4Do[S=>	MnHDNlQ4PDZ3N{S=
NRK-52E	MV;GeY5kfGmxbjDhd5NigQ>?	NYG4Sm9mOTBizszN	M1jtZ2ROW09?	MnGybY5pcWKrdIOgRY5oKEmLLXnu[JVk\WRiU2TBWFMhdnWlbHXhdkB1emGwc3zvZ4F1cW:wIHHu[EB1cGViZYjwdoV{e2mxbjDv[kBVT0ZvzsKxMEBkd2yuYXflckBKXiCjbnSg[oljem:wZXP0bY4>	M37UXVI2ODh6MECy
PC12	NXXtcpFoT3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	NIrmfnN,OTJwNTFOwG0>	NVXKcpNnTE2VTx?=	MVnwdoV3\W62czDUV2EucW6mdXPl[EBv\XW{aYTlJIZwem2jdHnvci=>	NXz5RVFEOjVzMkizPFY>
HPMCs	MU\GeY5kfGmxbjDhd5NigQ>?			NWPqZZVZemW4ZYLz[ZMh\XCrdHjlcIlidCC2bzDt[ZNmdmOqeX3hcEB1emGwc3n0bY9vKG:oIHj1cYFvKHCncnn0c45m[WxibXXzc5Rp\WyrYXygZ4VtdHN?	NFXac2gzPjB2NUe4NC=>
A549	MkPSSpVv[3Srb36gZZN{[Xl?	NVjRWoFIhjVyIN88US=>	NEex[HVFVVOR	MV7h[oZm[3S\|IITo[UB3cXKjbDDsbYZmKGO7Y3zlJIFv\CCqb4P0JJJme3CxboPl	NFnsN4QzPjdzMUe0PC=>
RAW264.7	MmXCSpVv[3Srb36gZZN{[Xl?	MnvUglMxKM7:TR?=	MVvEUXNQ	NYD3[G5TemWmdXPld{Bxem9vaX7mcIFudWG2b4L5JIdmdmViZYjwdoV{e2mxbh?=	MnPPNlY4OTh3OE[=
MEMM	NHPsfItMcW6jc3WgZZN{[Xl?	MYWxOUDDvU1?	NV7LUm51TE2VTx?=	MVfk[YNz\WG\|ZYOgZYNmfHmuYYTpc44hd2ZiaHnzeI9v\SCKMx?=	MmXQNlY6OjF3ME[=
MEMM	NGnObXdIem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	MmTQglIxKML3TR?=	MYHEUXNQ	M4XHeIlvcGmkaYTzJINmdGxicILvcIln\XKjdHnvci=>	MWSyOlkzOTVyNh?=
MEMM	MoPZRZBweHSxc3nzJIF{e2G7	MYWxOUDDvU1?	MWPEUXNQ	MU\pcoR2[2W\|IITo[UBxemW\|ZX7j[UBw\iC2aHWgZZBweHSxc3nzJJBzd3SnaX6sJINt\WG4ZXSgR4F{eGG\|ZT2z	MmrYNlY6OjF3ME[=
T47D	NX\BUm9qT3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	NYrG[ngzOTBizszN	MkWySG1UVw>?	NFXhTIJKSzVyPUeyJI5O	MmrENVg{QDF2NES=
ZR-75-1	MlnSS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	MXmxNEDPxE1?	NWqxRWVzTE2VTx?=	MV;JR\|UxRTd7IH7N	MlfpNVg{QDF2NES=
BT474	M4rLWWdzd3e2aDDpcohq[mm2b4L5JIF{e2G7	NFu5TFMyOCEQvF2=	MmX6SG1UVw>?	MW\JR\|UxRTh4IH7N	M{TzTVE5OzhzNES0
HCC1954	NVyyb2RbT3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	M{T0cVExKM7:TR?=	M1zZS2ROW09?	NXfiNXl{UUN3ME2xNVkhdk1?	MX6xPFM5OTR2NB?=
MDA-MB-453	NXTCTYFsT3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	M3voT\|ExKM7:TR?=	MYTEUXNQ	NYDXZ5JnUUN3ME25O\|Uhdk1?	MUSxPFM5OTR2NB?=
MDA-MB-468	NYjNTVR{T3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	MWSxNEDPxE1?	MXnEUXNQ	NWiy[oRoUUN3ME2zNlA5KG6P	MXWxPFM5OTR2NB?=
SkBr3	MkjLS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	NIDufHMyOCEQvF2=	M1f5O2ROW09?	NXPLdllEUUN3ME6xNEwxODBibl2=	NYq2NVBqOTh\|OEG0OFQ>
MDA-MB-231	NWq0S3BbT3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	MYmxNEDPxE1?	NXvNfXhUTE2VTx?=	MmPoTWM2OD5zMDywNFAhdk1?	MXGxPFM5OTR2NB?=
HCT116	NEjONG5Iem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	MmLPNVAh\|ryP	NIP0OZJFVVOR	Ml;mTWM2OD13OEO2JI5O	MYexPFM5OTR2NB?=
HT29	MlT0S5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	MYexNEDPxE1?	NUDNTWR7TE2VTx?=	MYjJR\|UxRjFyLECwNEBvVQ>?	M3jDNVE5OzhzNES0
HFF	NI\vOVZIem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	MkToNVAh\|ryP	M{fsW2ROW09?	NXrTeVRnUUN3ME23OlE2KG6P	NEfrU5YyQDN6MUS0OC=>
HN5	MVPHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?	NXHwRVB1OTBizszN	NGG4VG5FVVOR	M{fIUGlEPTB-MUCsNFAxKG6P	MYmxPFM5OTR2NB?=
786-0	NVzaTWhDT3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	MlLMNVAh\|ryP	MUTEUXNQ	M{XGd2lEPTB;NECwPUBvVQ>?	NHvTcJAyQDN6MUS0OC=>
H157	MkXtS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	NI[2U3kyOCEQvF2=	M{fqO2ROW09?	NX\VVpE1UUN3ME2yOlQzKG6P	NUWyUJF2OTh\|OEG0OFQ>
NCI-H460	Mk\vS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	MnfmNVAh\|ryP	NYnuZ\|hxTE2VTx?=	MWjJR\|UxRjJuNUCwJI5O	M1\kNlE5OzhzNES0
SKOV-3	MlXSS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	NULqU5o2OTBizszN	NHnqbVBFVVOR	NGfHSGlKSzVyPUKxNlYhdk1?	Ml3zNVg{QDF2NES=
OVCAR-3	NFLBW5JIem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	MVWxNEDPxE1?	Mn;hSG1UVw>?	MV\JR\|UxRTJ7MUigcm0>	MUmxPFM5OTR2NB?=
BXPC3	MXTHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?	MYqxNEDPxE1?	NUG2VG5PTE2VTx?=	NXex[XVWUUN3ME2zNVQyKG6P	M2fkT\|E5OzhzNES0
MiaPaCa	NXLMfIc5T3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	MmLtNVAh\|ryP	M1;2fGROW09?	Mn3oTWM2OD13NEOzJI5O	M2\NTVE5OzhzNES0
PANC-1	MkfTS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	MXKxNEDPxE1?	NI\qWGJFVVOR	NV;POHNCUUN3ME24OlgyKG6P	M{faVlE5OzhzNES0
LNCaP	MoPiS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	MY[xNEDPxE1?	NHzROoJFVVOR	NFvkdo9KSzVyPUG0O{BvVQ>?	M4TWUlE5OzhzNES0
DU145	NW\Hbm9mT3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	MV2xNEDPxE1?	MUnEUXNQ	NFT1OZJKSzVyPUO4NVIhdk1?	MlHhNVg{QDF2NES=
PC3	MojTS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	Mn\QNVAh\|ryP	NXfrO4ZkTE2VTx?=	NHjaZYVKSzVyPkGwMFAxOCCwTR?=	M2KyfVE5OzhzNES0
BT474	Mln0T4lv[XOnIHHzd4F6	MWixNEDPxE1?	MVzEUXNQ	NUXTepVJcW6qaXLpeJMheEeVS{ROtkB4cXSqIFnDOVAhd2ZiMU[wJI5O	MYOxPFM5OTR2NB?=
786-0	NGTacpFMcW6jc3WgZZN{[Xl?	M4Hz[lExKM7:TR?=	MVjEUXNQ	M{fzeolvcGmkaYTzJJBIW0t\|zsKge4l1cCCLQ{WwJI9nKDF3MDDuUS=>	M363clE5OzhzNES0
LNCaP	MkewT4lv[XOnIHHzd4F6	MWSxNEDPxE1?	MYHEUXNQ	M1jaT4lvcGmkaYTzJJBIW0t\|zsKge4l1cCCLQ{WwJI9nKDR\|IH7N	NUL1TWU{OTh\|OEG0OFQ>
PC3	NFLSeWJMcW6jc3WgZZN{[Xl?	NIX5VmQyOCEQvF2=	M3;ZemROW09?	MV7pcohq[mm2czDwS3NMO87{IIfpeIghUUN3MDDv[kA1QSCwTR?=	MoTVNVg{QDF2NES=
KARPAS-231	MUjHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?	NUTobJB5OTBizszN	MVjEUXNQ	M4r1[2VEPTB;NEGgcm0>	NWjhVoFZOTlyNkS3N\|A>
CCRFSB	M{TvfWdzd3e2aDDpcohq[mm2b4L5JIF{e2G7	MofsNVAh\|ryP	M1HFe2ROW09?	M2fGRmVEPTB;MUW1JI5O	M2fRT\|E6ODZ2N{Ow
SUP B15	MWPHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?	MUOxNEDPxE1?	NWDTRYdbTE2VTx?=	NUTGRox3TUN3ME2xPVchdk1?	M1\HdlE6ODZ2N{Ow
SD-1	NIflO\|hIem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	M2fIXVExKM7:TR?=	NXq4T5BsTE2VTx?=	NYGyfWYxTUN3ME2zNlAhdk1?	M4n0NVE6ODZ2N{Ow
RS4;11	MkToS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	MV[xNEDPxE1?	MXLEUXNQ	MYnFR\|UxRTZ3NDDuUS=>	NH3ISoIyQTB4NEezNC=>
MN-60	MXvHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?	NYnjWFlPOTBizszN	MmLrSG1UVw>?	NYHneJJXTUN3ME2zOlAzKG6P	M4rTWFE6ODZ2N{Ow
Tanoue	NYHGZ2ZoT3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	MXGxNEDPxE1?	NIrPeFJFVVOR	MXTFR\|UxRTR3MUegcm0>	NH;EbFUyQTB4NEezNC=>
RCH-ACV	NVHSUYZPT3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	M3\helExKM7:TR?=	MnPwSG1UVw>?	NVS2NWZETUN3ME2xOVIhdk1?	NIHGVmQyQTB4NEezNC=>
SEM	NIX2dYZIem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	Mkf6NVAh\|ryP	MmjVSG1UVw>?	NH25dG5GSzVyPUKwNkBvVQ>?	NWjLd41IOTlyNkS3N\|A>
KASUMI-2	MWDHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?	Mn\VNVAh\|ryP	Ml73SG1UVw>?	NFnLZ21GSzVyPUKyOUBvVQ>?	NXTqWopUOTlyNkS3N\|A>
REH	MkHFS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	NFjFTHgyOCEQvF2=	MW\EUXNQ	NH24SHpGSzVyPUK4PEBvVQ>?	M1zJb\|E6ODZ2N{Ow
697	NFnxXGxIem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	MljONVAh\|ryP	M3n3TGROW09?	NWHDPWRTTUN3ME2zN\|ghdk1?	MVmxPVA3PDd\|MB?=
NALM-6	M3rRR2dzd3e2aDDpcohq[mm2b4L5JIF{e2G7	MmPDNVAh\|ryP	M{TXNGROW09?	MnXYSWM2OD12MkGgcm0>	NXzKT4NxOTlyNkS3N\|A>
MHH-CALL–3	NXL6cI9CT3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	MXKxNEDPxE1?	M1SyS2ROW09?	M4i5UmVEPTB;OEGyJI5O	Mnj3NVkxPjR5M{C=
MHH-CALL–2	MnP2S5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	NYLZR2E6OTBizszN	MnnUSG1UVw>?	M13Yb2VEPTB;MkGxOEBvVQ>?	MkHzNVkxPjR5M{C=
J.GAMMA-1	NV7VVG81T3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	NX3DPXkyOTBizszN	M4rIXGROW09?	MnK5SWM2OD14NTDuUS=>	MUOxPVA3PDd\|MB?=
JR45.01	MmPKS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	NV3lZ4xWOTBizszN	M{\LWmROW09?	MkfuSWM2OD14ODDuUS=>	MkjTNVkxPjR5M{C=
A3	MU\Hdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?	MkfXNVAh\|ryP	NVPXZY05TE2VTx?=	MYnFR\|UxRTZ7IH7N	M3rM[lE6ODZ2N{Ow
I 2.1	M1j2Nmdzd3e2aDDpcohq[mm2b4L5JIF{e2G7	NYP2PJpTOTBizszN	M1PWe2ROW09?	NFPTNnZGSzVyPUezJI5O	MoTDNVkxPjR5M{C=
MOLT-3	MonlS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	MlzzNVAh\|ryP	NFjyVWZFVVOR	MX3FR\|UxRTd2IH7N	MYGxPVA3PDd\|MB?=
P116	MVTHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?	NWCxNmFYOTBizszN	NIjNR3BFVVOR	M2jOVGVEPTB;N{igcm0>	NVfnW41xOTlyNkS3N\|A>
J.Cam1.6	MXLHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?	NX;sV4N{OTBizszN	MX3EUXNQ	NHPGZ2hGSzVyPUe5JI5O	MVOxPVA3PDd\|MB?=
I 9.2	M1;t[Wdzd3e2aDDpcohq[mm2b4L5JIF{e2G7	MVmxNEDPxE1?	MXzEUXNQ	MXHFR\|UxRThyIH7N	NVHYT282OTlyNkS3N\|A>
LOUCY	NYTvPHVGT3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	NIrTdJkyOCEQvF2=	MnXMSG1UVw>?	M3PTRWVEPTB;MUG3JI5O	NGfORZAyQTB4NEezNC=>
J.RT3-T3.5	M3TMOWdzd3e2aDDpcohq[mm2b4L5JIF{e2G7	MYKxNEDPxE1?	NXLsXWVXTE2VTx?=	NH7uUVlGSzVyPUGyN{BvVQ>?	NITjSnEyQTB4NEezNC=>
800000	MWXHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?	M2\yVlExKM7:TR?=	MV;EUXNQ	MUTFR\|UxRTF4MzDuUS=>	MmXuNVkxPjR5M{C=
Jurkat	MlHvS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	M2\1blExKM7:TR?=	MYrEUXNQ	NEPWbWNGSzVyPUKyOUBvVQ>?	NGDUWYQyQTB4NEezNC=>
MOLT-4	M1TXe2dzd3e2aDDpcohq[mm2b4L5JIF{e2G7	MlvONVAh\|ryP	MoPsSG1UVw>?	M{XxUWVEPTB;MkOyJI5O	NUnCbpQ1OTlyNkS3N\|A>
Molt-16	MYLHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?	NEPC[FQyOCEQvF2=	M4TBbGROW09?	Ml3kSWM2OD1{NEGgcm0>	MmHWNVkxPjR5M{C=
CEM/C3	NILFSZFIem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	MVqxNEDPxE1?	MlHpSG1UVw>?	M2P0TWVEPTB;MkW3JI5O	NI\XbW4yQTB4NEezNC=>
CEM/C2	NFTvXmhIem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	NWPPVYJyOTBizszN	NIO3bllFVVOR	MVzFR\|UxRTJ5MTDuUS=>	MUexPVA3PDd\|MB?=
CCRFCEM	MkXpS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	NXLGfIZUOTBizszN	Mm\LSG1UVw>?	MXvFR\|UxRTN{NzDuUS=>	M33Ib\|E6ODZ2N{Ow
CEM/C1	NV\DO4pKT3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	NYjMNXdtOTBizszN	M1;pWmROW09?	NVqzZWZJTUN3ME2zPFIhdk1?	NIHvZYkyQTB4NEezNC=>
SUPTI[VB]	MmHzS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	MYOxNEDPxE1?	M1HsdmROW09?	MXHFR\|UxRTZzOTDuUS=>	NF60TpkyQTB4NEezNC=>
CCRF–HSB-2	NHvxRWZIem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	MX6xNEDPxE1?	NFjQelRFVVOR	MljySWM2OD1{MUG3JI5O	M{PYfVE6ODZ2N{Ow
I 2.1	M3fQUWFxd3C2b4Ppd{Bie3OjeR?=	MnPpNVAh\|ryP	NWrFRVZVTE2VTx?=	Mn3LbY5lfWOnczDhdI9xfG:\|aYO=	M{\2WFE6ODZ2N{Ow
I 9.2	Mkj5RZBweHSxc3nzJIF{e2G7	NX\2OpZtOTBizszN	NXHrNVg6TE2VTx?=	MkPNbY5lfWOnczDhdI9xfG:\|aYO=	M2PZ[\|E6ODZ2N{Ow
A3	MoPzRZBweHSxc3nzJIF{e2G7	M2fVclExKM7:TR?=	NXzUdY9kTE2VTx?=	NYOyPYJMcW6mdXPld{BieG:ydH;zbZM>	M4jicFE6ODZ2N{Ow
RD	NWe3dI5OT3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	M2D2bVExKM7:TR?=		NYnsVmltUUN3ME6xNEDPxE1?	MlnTNlA4PDB4MkO=
Rh41	MYPHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?	M{\XZVExKM7:TR?=		NGLo[nRKSzVyPUOzMlghdk1?	MoX6NlA4PDB4MkO=
Rh18	Mn7rS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	MVSxNEDPxE1?		M3XSUGlEPTB;M{CzJI5O	M1TYZVIxPzRyNkKz
Rh30	NGfGT5dIem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	Moj0NVAh\|ryP		NWjBTmJ4UUN3ME20MlgyKM7:TR?=	M3q4cVIxPzRyNkKz
BT-12	NYTX[VZ7T3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	M3jrUFExKM7:TR?=		MVHJR\|UxRjFyIN88US=>	MUiyNFc1ODZ{Mx?=
CHLA-266	NH7OUnBIem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	M3PkOlExKM7:TR?=		MUPJR\|UxRTFwMkKg{txO	M{\HTlIxPzRyNkKz
TC-71	NXXod3FmT3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	NV\HZnZKOTBizszN		NVfBdWROUUN3ME2yMlUzKM7:TR?=	MlfQNlA4PDB4MkO=
CHLA-9	NF;seGlIem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	NIHnVIoyOCEQvF2=		NGS0fnhKSzVyPUW5NUBvVQ>?	NIK0VGozODd2ME[yNy=>
CHLA-10	M{fjdGdzd3e2aDDpcohq[mm2b4L5JIF{e2G7	MoTJNVAh\|ryP		MV3JR\|UxRTFyMjDuUS=>	NYfEWHhEOjB5NEC2NlM>
CHLA-258	NXjJdnA5T3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	NUf5bWpbOTBizszN		MU\JR\|UxRTFwMEWg{txO	M{O3[\|IxPzRyNkKz
GBM2	NUjMc3QxT3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	NHvZUGoyOCEQvF2=		M3\aPWlEPTB;OT6xOUDPxE1?	M3X6WFIxPzRyNkKz
NB-1643	MlnBS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	NV3vN2VDOTBizszN		M1yybGlEPTB;NT60JO69VQ>?	NVOzd2FCOjB5NEC2NlM>
NB-Ebc1	MVzHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?	MkDSNVAh\|ryP		NUfTNJhOUUN3ME6xNEDPxE1?	M3O2OVIxPzRyNkKz
CHLA-90	NUfISmpyT3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	NXPmcI43OTBizszN		NH3iV4hKSzVyPkGwJO69VQ>?	NX70TIlMOjB5NEC2NlM>
CHLA-136	MVHHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?	NYn2[3l4OTBizszN		NYKxV4x7UUN3ME6xNEDPxE1?	MknXNlA4PDB4MkO=
NALM-6	MnLXS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	NV;j[ZJPOTBizszN		MWLJR\|UxRTJ4NTDuUS=>	NXrHXHFJOjB5NEC2NlM>
COG-LL-317	NWrtT3lET3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	M2nwO\|ExKM7:TR?=		NYH5cmdVUUN3ME22MlQ6KG6P	NUXCbHByOjB5NEC2NlM>
RS4;11	NI\LZ3dIem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	MYKxNEDPxE1?		NEXC[HVKSzVyPUG0O{BvVQ>?	MWKyNFc1ODZ{Mx?=
MOLT-4	MV7Hdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?	NX\TcFZ2OTBizszN		MWLJR\|UxRTRyIH7N	NHnpWYczODd2ME[yNy=>
CCRF-CEM	NWDhTVNOT3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	MYSxNEDPxE1?		MofLTWM2OD1{Nkigcm0>	NIL1bYIzODd2ME[yNy=>
Kasumi-1	MXfHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?	MYixNEDPxE1?		MlLvTWM2OD1zMEegcm0>	NWX3[WxOOjB5NEC2NlM>
Karpas-299	NVyyWVNpT3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	M{fwTVExKM7:TR?=		NFTjfYVKSzVyPUKuPVMh\|ryP	MlLVNlA4PDB4MkO=
Ramos-RA1	NHfZcY5Iem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	MXyxNEDPxE1?		MVrJR\|UxRTdwM{Wg{txO	MXeyNFc1ODZ{Mx?=
H1299	MYPLbY5ie2ViYYPzZZk>	MYmxNEDPxE1?		NXLidWVscW6qaXLpeJMhUUuES1WtbY5lfWOnZDDBb5QhSWO2aY\heIlwdg>?	M4jMT\|IyQTB6NkG2

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. (Only for Reference)
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 (Only for Reference)

References

Solubility (25°C)

In vitro	DMSO	73 mg/mL (197.6 mM)
	Water	Insoluble
	Ethanol	Insoluble

* 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	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)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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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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