Tivantinib (ARQ 197)

Catalog No.S2753

For research use only.

Tivantinib (ARQ 197) is the first non-ATP-competitive c-Met inhibitor with Ki 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.

Tivantinib (ARQ 197) Chemical Structure

CAS No. 905854-02-6

Selleck's Tivantinib (ARQ 197) has been cited by 37 publications

Purity & Quality Control

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Biological Activity

Description Tivantinib (ARQ 197) is the first non-ATP-competitive c-Met inhibitor with Ki 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.
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 Km of ATP, exposure of c-Met to 0.5 μM ARQ-197 decreased the Vmax of c-Met by approximately 3-fold. The ability of ARQ-197 to decrease the Vmax 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 Ki 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 M1zue2tqdmG|ZTDhd5NigQ>? MXT+NVAh|ryP NHTDPWtqdmirYnn0d{BkNU2ndDDwbI9{eGixconsZZRqd25iYX7kJIRwf26|dILlZY0h[y2PZYSgd4lodmGuaX7nJJBifGi5YYnz MWmyNFQ5PDBzOB?=
HT29 NHG4XnFMcW6jc3WgZZN{[Xl? NVXIfZFIhjFyIN88US=> M{\nRYlvcGmkaYTzJIMuVWW2IIDoc5NxcG:{eXzheIlwdiCjbnSg[I94dnO2cnXhcUBkNU2ndDDzbYdv[WyrbnegdIF1cHejeYO= NU\xZWRMOjB2OESwNVg>
MDA-MB-231 NUTZSnBDU2mwYYPlJIF{e2G7 MWL+NVAh|ryP MoC1bY5pcWKrdIOgZ{1O\XRicHjvd5Bpd3K7bHH0bY9vKGGwZDDkc5dve3S{ZXHtJIMuVWW2IIPp[45idGmwZzDwZZRpf2G7cx?= MV6yNFQ5PDBzOB?=
NCI-H441 M2frSWtqdmG|ZTDhd5NigQ>? MWj+NVAh|ryP M1TEfYlvcGmkaYTzJIMuVWW2IIDoc5NxcG:{eXzheIlwdiCjbnSg[I94dnO2cnXhcUBkNU2ndDDzbYdv[WyrbnegdIF1cHejeYO= MnPSNlA1QDRyMUi=
SK-MEL-28 MljvS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl? M2OxPVM{KM7:TR?= M1K1ZmlEPTB-M{Og{txO MYmyNFQ5PDBzOB?=
NCI-H661 MnvBS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl? NEH1fVM{OyEQvF2= MnjlTWM2OD5|MzFOwG0> NY\XOIIzOjB2OESwNVg>
NCI-H446 MUnHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>? M4nLU|M{KM7:TR?= MlzWTWM2OD15IN88US=> MX6yNFQ5PDBzOB?=
MDA-MB-231 NIrxblhIem:5dHigbY5pcWKrdH;yfUBie3OjeR?= M4X1OFM{KM7:TR?= M3TUbGlEPTB;MD61OUDPxE1? MlLUNlA1QDRyMUi=
DLD-1 NVf5flhOT3Kxd4ToJIlvcGmkaYTvdpkh[XO|YYm= NEfBTVE{OyEQvF2= MVrJR|UxRTBwNUOg{txO M3eyNVIxPDh2MEG4
A549 NYPPOVhmT3Kxd4ToJIlvcGmkaYTvdpkh[XO|YYm= M{fCbVM{KM7:TR?= MYrJR|UxRTBwNUmg{txO NVO1WZo6OjB2OESwNVg>
SK-OV-3 Ml\PS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl? M33FdlM{KM7:TR?= NHzyTGNKSzVyPUCuOlYh|ryP M2\BeVIxPDh2MEG4
NCI-H460 NUf2fnB1T3Kxd4ToJIlvcGmkaYTvdpkh[XO|YYm= MVSzN{DPxE1? NVnVSotIUUN3ME2wMlYh|ryP M2LVWVIxPDh2MEG4
A375 NGe2UXpIem:5dHigbY5pcWKrdH;yfUBie3OjeR?= NVm5e4lmOzNizszN NVfPOFBNUUN3ME2wMlQzKM7:TR?= MojlNlA1QDRyMUi=
NCI-H441 NWG0XJpRT3Kxd4ToJIlvcGmkaYTvdpkh[XO|YYm= MUCzN{DPxE1? M3TjZWlEPTB;MD6zJO69VQ>? NYr2THpbOjB2OESwNVg>
HT29 MVLHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>? MYqzN{DPxE1? MlnyTWM2OD1yLkS5JO69VQ>? NGH5VI8zODR6NECxPC=>
MKN-45 MUDHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>? NF\qOno{OyEQvF2= M1jmbmlEPTB;MD61PEDPxE1? MmW3NlA1QDRyMUi=
HT29 MXzBdI9xfG:|aYOgZZN{[Xl? M1n2bp4yOCEQvF2= NIixO2p{cWewaX\pZ4FvfGy7IHnu[JVk\XNiYYDvdJRwe2m|IHL5JFgxNTlyJT6= M3Xo[FIxPDh2MEG4
MKN-45 NFz4O2dCeG:ydH;zbZMh[XO|YYm= MkXJglExKM7:TR?= NH;GXnR{cWewaX\pZ4FvfGy7IHnu[JVk\XNiYYDvdJRwe2m|IHL5JFgxNTlyJT6= NVW2OJZnOjB2OESwNVg>
MDA-MB-231 Mn\jRZBweHSxc3nzJIF{e2G7 NF[2dYF,OTBizszN M3q3WI1w\GW|dHz5JIlv\HWlZYOgZZBweHSxc3nzJIJ6KDN3JT6= M1exeVIxPDh2MEG4
MDA-MB-231/TGL M{\5W2dzd3e2aDDpcohq[mm2b4L5JIF{e2G7 MkXyglExOCEQvF2= MX7HTVUxRTFwMjFOwG0> NFvaNVEzOjB{N{[5NC=>
1833/TGL Ml\LS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl? Ml3PglExOCEQvF2= M4fzTGdKPTB;Mz63JO69VQ>? M17leFIzODJ5Nkmw
EBC1 M{T6XGN6fG:2b4jpZ:Kh[XO|YYm= M1jObp4yOCEQvF2= MVrpcohq[mm2czD0bIUh[2WubDDndo94fGhw MYGyN|U6QDJ5Nh?=
SNU638 NF3WWI5EgXSxdH;4bYPDqGG|c3H5 MWn+NVAh|ryP MVHpcohq[mm2czD0bIUh[2WubDDndo94fGhw MnvINlM2QTh{N{[=
A549 MXfDfZRwfG:6aXRCpIF{e2G7 MnvYglExKM7:TR?= NFPQT5Bvd3RiYX\m[YN1 MW[yN|U6QDJ5Nh?=
H460 NYjtZWxbS3m2b4TvfIlkyqCjc4PhfS=> NW[wR3VLhjFyIN88US=> Mnvkco91KGGoZnXjeC=> MVmyN|U6QDJ5Nh?=
HCC827 Mk\CR5l1d3SxeHnjxsBie3OjeR?= MVX+NVAh|ryP NYX2TWdkdm:2IHHm[oVkfA>? NU[4bYhbOjN3OUiyO|Y>
A549 MmLzSpVv[3Srb36gZZN{[Xl? NUiwNpBGOTBizszN MWXkbZNzfXC2czDtbYNzd3S3YoXs[S=> NH[2VJozOzV7OEK3Oi=>
EBC1 MVLGeY5kfGmxbjDhd5NigQ>? M2D6SFExKM7:TR?= NGP2XZVlcXO{dYD0d{BucWO{b4T1ZpVt\Q>? MYWyN|U6QDJ5Nh?=
H460 Mn;ySpVv[3Srb36gZZN{[Xl? MlL5NVAh|ryP M4\Vd4lvcGmkaYTzJJR2[nWuaX6gdI9tgW2ncnn6ZZRqd25? NEDEU4kzPTNzM{CxNC=>
K562/VCR MluyR5l1d3SxeHnjxsBie3OjeR?= NHzDW3h,OTBizszN M1nSZ5Npd3e|IHP5eI91d3irYzDhZ5Rqfmm2eR?= MmDPNlU{OTNyMUC=
CEM/VBL Mk\WR5l1d3SxeHnjxsBie3OjeR?= M2rFWp4yOCEQvF2= M4TROZNpd3e|IHP5eI91d3irYzDhZ5Rqfmm2eR?= NFHJcVMzPTNzM{CxNC=>
U266 M1fYTGN6fG:2b4jpZ:Kh[XO|YYm= NYDGNGZThjNizszNxsA> NUHpZ4pbUUN3ME2xMlEh|ryP M3zUdVI2QDFyMEGz
OPM-2 NXTXenpwS3m2b4TvfIlkyqCjc4PhfS=> MnXqglMh|ryPwrC= MVjJR|UxRTFwODFOwG0> NUHJcGVIOjV6MUCwNVM>
MM.1S MXrDfZRwfG:6aXRCpIF{e2G7 M3PXfp4{KM7:TdMg NFfuZ4hKSzVyPUGuOkDPxE1? M3fnRVI2QDFyMEGz
MM.1R MV7Hdo94fGhiaX7obYJqfG:{eTDhd5NigQ>? MmHDN{DPxE4EoB?= Mlq1bY5pcWKrdIOgZ4VtdCCpcn;3eIgh[nliNEml MV6yOVgyODBzMx?=
RPMI-8226 MVzDfZRwfG:6aXRCpIF{e2G7 M4K0UZ4{KM7:TdMg NGTqe3dKSzVyPUCuPUDPxE1? NFHQVpgzPThzMECxNy=>
ANBL-6 NFrx[45EgXSxdH;4bYPDqGG|c3H5 NVi5eIpLOSEQvF5CpC=> M3G0WIlv\HWlZYOgZ4VtdCCmZXH0bEBjgSCvb4LlJJRp[W5iNUCl NETTfJkzPThzMECxNy=>
ANLB-6/V10R NXrlNWNGS3m2b4TvfIlkyqCjc4PhfS=> NHOzWVcyKM7:TdMg MXXpcoR2[2W|IHPlcIwh\GWjdHigZpkhdW:{ZTD0bIFvKDVyJR?= NGjMO5EzPThzMECxNy=>
KAS-6/1 MkfGR5l1d3SxeHnjxsBie3OjeR?= MYGxJO69VcLi MX\pcoR2[2W|IHPlcIwh\GWjdHigZpkhdW:{ZTD0bIFvKDVyJR?= NWnpeos6OjV6MUCwNVM>
KAS-6/V10R M3nDW2N6fG:2b4jpZ:Kh[XO|YYm= MYqxJO69VcLi NFe1SW5qdmS3Y3XzJINmdGxiZHXheIgh[nlibX;y[UB1cGGwIEWwKS=> NF3EOnkzPThzMECxNy=>
KAS-6/R10R NGnJfnNEgXSxdH;4bYPDqGG|c3H5 MnPuNUDPxE4EoB?= NH;JbnZqdmS3Y3XzJINmdGxiZHXheIgh[nlibX;y[UB1cGGwIEWwKS=> MkfxNlU5OTByMUO=
8226/S NISxc|NIem:5dHigbY5pcWKrdH;yfUBie3OjeR?= NGDObng{KM7:TdMg NX;SOmpbcW6qaXLpeJMh[2WubDDndo94fGhiYomgOVQm MoCwNlU5OTByMUO=
8226/LR-5 M3LVTWdzd3e2aDDpcohq[mm2b4L5JIF{e2G7 NXLl[pdwOyEQvF5CpC=> Ml\zbY5pcWKrdIOgZ4VtdCCpcn;3eIgh[nliNUSl MUKyOVgyODBzMx?=
Huh7 NXK0U|RGS3m2b4TvfIlkyqCjc4PhfS=> M{TaVp41NjhizszNxsA> MlvDSG1UVw>? MoW2TWM2OD17Lkmgcm0> MmrZNlYzPTl{NUC=
Hep3B MWXDfZRwfG:6aXRCpIF{e2G7 NYrk[lVohjRwODFOwG3DqA>? M2X3PGROW09? Mlq3TWM2OD12NEiuO{BvVQ>? NXHLPVdUOjZ{NUmyOVA>
HepG2 MYTDfZRwfG:6aXRCpIF{e2G7 MkXhglQvQCEQvF5CpC=> NV7FfHJVTE2VTx?= NEHvOVFKSzVyPUGzPU44PyCwTR?= NH\YOoczPjJ3OUK1NC=>
Chang MmPQR5l1d3SxeHnjxsBie3OjeR?= Ml7lglQvQCEQvF5CpC=> M3;zUGROW09? MVzJR|UxRTR2OD63JI5O MoPMNlYzPTl{NUC=
Huh7 NFnNeI5HfW6ldHnvckBie3OjeR?= M3z4WlEvPiEQvF5CpC=> NHz4b|VFVVOR MmnKZ4F2e2W|IHGgS|IwVSClZXzsJIN6[2ynIHHydoV{fA>? NEeyRmkzPjJ3OUK1NC=>
Hep3B NIHQc3lHfW6ldHnvckBie3OjeR?= MYSxMlYh|ryPwrC= M3PJWWROW09? MlH6Z4F2e2W|IHGgS|IwVSClZXzsJIN6[2ynIHHydoV{fA>? MVGyOlI2QTJ3MB?=
HepG2 NF7MS3hHfW6ldHnvckBie3OjeR?= NIW1TpcyNjZizszNxsA> MlvwSG1UVw>? M1jWb4NifXOnczDhJGczN01iY3XscEBkgWOuZTDhdpJme3R? MW[yOlI2QTJ3MB?=
Chang MYjGeY5kfGmxbjDhd5NigQ>? NGTj[|kyNjZizszNxsA> M3fQTmROW09? M3jQ[INifXOnczDhJGczN01iY3XscEBkgWOuZTDhdpJme3R? NUS3PYVyOjZ{NUmyOVA>
MHCC97L NH\uW4pIem:5dHigbY5pcWKrdH;yfUBie3OjeR?= MWn+NVAh|ryP MnrMSG1UVw>? NWjyNng2UUN3ME2zNVUhdk1? NF;zTHIzPjR3OEm1Ny=>
MHCC97H M2XKcGdzd3e2aDDpcohq[mm2b4L5JIF{e2G7 M1nneZ4yOCEQvF2= NGC1TnNFVVOR MWXJR|UxRTN4OPMAjUBvVQ>? MkH5NlY1PTh7NUO=
Huh7 MoT3S5Jwf3SqIHnubIljcXSxcomgZZN{[Xl? MVj+NVAh|ryP NWDufHlrTE2VTx?= NYXa[2kzUUN3ME2yOlUhdk1? Mo\FNlY1PTh7NUO=
HepG2 NHW2bplIem:5dHigbY5pcWKrdH;yfUBie3OjeR?= M2\GW54yOCEQvF2= M3HtRWROW09? M1vsb2lEPTB;M{myJI5O NFrXUXczPjR3OEm1Ny=>
MHCC97L MX3GeY5kfGmxbjDhd5NigQ>? Mnq4NUDPxE4EoB?= NYrTNJN1TE2VTx?= NYjyboUzcW6mdXPld{BucWO{b4T1ZpVt\XNiZHXwc4x6dWW{aYrheIlwdg>? MYWyOlQ2QDl3Mx?=
Huh7 M132R2Z2dmO2aX;uJIF{e2G7 M2nZNFEh|ryPwrC= NGGwbFZFVVOR MnO3bY5lfWOnczDtbYNzd3S3YoXs[ZMh\GWyb3z5cYVzcXqjdHnvci=> M4i1TVI3PDV6OUWz
MHCC97L NE\qTmFCeG:ydH;zbZMh[XO|YYm= M2XjTVEh|ryPwrC= MkHCSG1UVw>? MYHpcoR2[2W|IHHwc5B1d3Orcx?= M2rOOVI3PDV6OUWz
Huh7 M1\SNWFxd3C2b4Ppd{Bie3OjeR?= MVixJO69VcLi Mn7LSG1UVw>? MVvpcoR2[2W|IHHwc5B1d3Orcx?= NUPEdGpGOjZ2NUi5OVM>
C3H 10T1/2 mouse fibroblasts M3WwNmtqdmG|ZTDhd5NigQ>? Mn:zNlUh|ryP MVHEUXNQ MVry[YR2[2W|IFjpd5RwdmViSEOgZY5lKEh2IHHj[ZR6dGG2aX;uJIxmfmWuc9Mg Ml;lNlA2OzR|NEW=
H23 NU[3c|V4T3Kxd4ToJIlvcGmkaYTvdpkh[XO|YYm= NEjGfnIzPSEQvF2= MVTEUXNQ M3XMXpNq\26rZnnjZY51dHliaX7obYJqfHNiY3XscEBoem:5dHiu MkXzNlA2OzR|NEW=
WM35 M3nPSGdzd3e2aDDpcohq[mm2b4L5JIF{e2G7 NXPVZ3d2OTBizszN MX3EUXNQ MU\zbYdvcW[rY3HueIx6KGmwaHnibZR{KGOnbHyg[5Jwf3SqLh?= MYSyNFU{PDN2NR?=
NIH 3T3 NFrYTmlIem:5dHigbY5pcWKrdH;yfUBie3OjeR?= NEX1XFEyOCEQvF2= MX\EUXNQ MkTa[I9meyCwb4SgbIF3\SCjIIPp[45q\mmlYX70JIlvcGmkaYTvdpkh\W[oZXP0 NGm1[WIzODV|NEO0OS=>
H838 MoL6S5Jwf3SqIHnubIljcXSxcomgZZN{[Xl? MXyxNEDPxE1? NHPVZ2JFVVOR MUDkc4V{KG6xdDDoZZZmKGFic3nncolncWOjboSgbY5pcWKrdH;yfUBm\m[nY4S= NV[1XFd2OjB3M{SzOFU>
H1395 MUTHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>? NUXIbnJ[OTBizszN NYq3fIJ1TE2VTx?= MWTkc4V{KG6xdDDoZZZmKGFic3nncolncWOjboSgbY5pcWKrdH;yfUBm\m[nY4S= MU[yNFU{PDN2NR?=
Quiescent S2 Mn\RT4lv[XOnIHHzd4F6 M4\6bFMxKM7:TR?= NYqwfopbTE2VTx?= M{noZYNwdXCuZYTlcJkh[WK{b3fheIV{KFSVQT3pcoR2[2WmIHj5dIVz[WOndInsZZRqd25ib3[gTFNMPG2nMzDobZN1d26ncx?= NH74TGEzOTVzOEmxOS=>
PC3 M{TOO2Fxd3C2b4Ppd{Bie3OjeR?= M17TW|IxKM7:TR?= M{D4emROW09? MorwbY5lfWOnczDhdI9xfG:|aYO= NWDHbo9TOjF5MEmxN|A>
Du145 MUPBdI9xfG:|aYOgZZN{[Xl? NHLLOoEzOCEQvF2= MYHEUXNQ MkL0bY5lfWOnczDhdI9xfG:|aYO= NHrCenczOTdyOUGzNC=>
LNCaP M322V2Fxd3C2b4Ppd{Bie3OjeR?= MXGyNEDPxE1? MX7EUXNQ MWnpcoR2[2W|IHHwc5B1d3Orcx?= NXKydW5KOjF5MEmxN|A>
LAPC-4 MWrBdI9xfG:|aYOgZZN{[Xl? NETYRZMzOCEQvF2= NVLEUVRHTE2VTx?= NFm3TlRqdmS3Y3XzJIFxd3C2b4Ppdy=> MX[yNVcxQTF|MB?=
LNCaP NFXreHpHfW6ldHnvckBie3OjeR?= MXyyNEDPxE1? NHi3TVdFVVOR M{iwToRm[3KnYYPld{BRW0Fic3XjdoV1cW:wIHHu[EBxPjViZYjwdoV{e2mxbjDs[ZZmdHN? NWGyeWppOjF5MEmxN|A>
LAPC-4 M4eyR2Z2dmO2aX;uJIF{e2G7 NUi0V5lNOjBizszN NHTZeVVFVVOR MmPj[IVkemWjc3XzJHBUSSC|ZXPy[ZRqd25iYX7kJJA3PSCneIDy[ZN{cW:wIHzleoVtew>? M1XXT|IyPzB7MUOw
Kasumi-1 MWrHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>? NHfCfJd,PTBizszN M2rCfWROW09? MXXpcohq[mm2czDj[YxtKHC{b3zp[oVz[XSrb36= MlzsNlM{QTB3M{[=
SKNO-1 NGr6OnhIem:5dHigbY5pcWKrdH;yfUBie3OjeR?= NIn3TpJ,PTBizszN NFH1eIhFVVOR MUXpcohq[mm2czDj[YxtKHC{b3zp[oVz[XSrb36= M{\l[VI{OzlyNUO2
Kasumi-1 M4jZbmtqdmG|ZTDhd5NigQ>? MYT+NVAh|ryP NH;TOY5FVVOR NF\EbYJz\WS3Y3XzJIV5eHKnc4Ppc44hd2ZiYXPleJlt[XSnZDDobZN1d26nIFizMOKh[y2taYVCpIFv\MLiYnPsMVI> NHqx[YEzOzN7MEWzOi=>
SKNO-1 MXfLbY5ie2ViYYPzZZk> MYD+NVAh|ryP MmLsSG1UVw>? NEPC[3Fz\WS3Y3XzJIV5eHKnc4Ppc44hd2ZiYXPleJlt[XSnZDDobZN1d26nIFizMOKh[y2taYVCpIFv\MLiYnPsMVI> MVyyN|M6ODV|Nh?=
A549 NWHRTHhKTnWwY4Tpc44h[XO|YYm= MXexNEDPxE1? MUXEUXNQ M{LTOIVvcGGwY3XzJI1qfG:2aXOgZ4F1[XO2cn;wbIU> MmLsNlQ4PDZ3N{S=
NRK-52E MofzSpVv[3Srb36gZZN{[Xl? M3i1flExKM7:TR?= MkHESG1UVw>? Ml\EbY5pcWKrdIOgRY5oKEmLLXnu[JVk\WRiU2TBWFMhdnWlbHXhdkB1emGwc3zvZ4F1cW:wIHHu[EB1cGViZYjwdoV{e2mxbjDv[kBVT0ZvzsKxMEBkd2yuYXflckBKXiCjbnSg[oljem:wZXP0bY4> M{m0R|I2ODh6MECy
PC12 M3r5Omdzd3e2aDDpcohq[mm2b4L5JIF{e2G7 MlTMglEzNjVizszN MmrQSG1UVw>? NF2zUYxxemW4ZX70d{BVW0FvaX7keYNm\CCwZYXybZRmKG[xcn3heIlwdg>? NYfRO|dCOjVzMkizPFY>
HPMCs NXnJXoIyTnWwY4Tpc44h[XO|YYm= NHPle5Jz\X[ncoPld{BmeGm2aHXsbYFtKHSxIH3ld4Vv[2i7bXHsJJRz[W6|aYTpc44hd2ZiaIXtZY4heGW{aYTvcoVidCCvZYPveIhmdGmjbDDj[Yxtew>? MljtNlYxPDV5OEC=
A549 MV3GeY5kfGmxbjDhd5NigQ>? MmjDglUxKM7:TR?= NFfyfIpFVVOR MorFZYZn\WO2czD0bIUhfmm{YXygcIln\SCleXPs[UBidmRiaH;zeEBz\XOyb37z[S=> NYPNU|dyOjZ5MUG3OFg>
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BT474 MlTYS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl? MlPINVAh|ryP NF[4SnhFVVOR M{XBemlEPTB;OE[gcm0> MonGNVg{QDF2NES=
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MDA-MB-231 NXrHeJNuT3Kxd4ToJIlvcGmkaYTvdpkh[XO|YYm= MWOxNEDPxE1? M3PlR2ROW09? NWO0[HJCUUN3ME6xNEwxODBibl2= NEXPNIoyQDN6MUS0OC=>
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SKOV-3 M{fBSmdzd3e2aDDpcohq[mm2b4L5JIF{e2G7 MVixNEDPxE1? M1u3TWROW09? NF7iUIZKSzVyPUKxNlYhdk1? MWqxPFM5OTR2NB?=
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697 MoL0S5Jwf3SqIHnubIljcXSxcomgZZN{[Xl? MUixNEDPxE1? NYXNN5Q4TE2VTx?= MW\FR|UxRTN|ODDuUS=> NIjEeFUyQTB4NEezNC=>
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MHH-CALL–3 M3Lt[mdzd3e2aDDpcohq[mm2b4L5JIF{e2G7 Mln6NVAh|ryP M{\0d2ROW09? MkHGSWM2OD16MUKgcm0> MVWxPVA3PDd|MB?=
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J.Cam1.6 NWnKbYhsT3Kxd4ToJIlvcGmkaYTvdpkh[XO|YYm= MX[xNEDPxE1? NX\RU4xJTE2VTx?= M2jX[GVEPTB;N{mgcm0> M4e5R|E6ODZ2N{Ow
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Jurkat NHvZe49Iem:5dHigbY5pcWKrdH;yfUBie3OjeR?= M3H1U|ExKM7:TR?= M4rldmROW09? M{W1SGVEPTB;MkK1JI5O M4fGXlE6ODZ2N{Ow
MOLT-4 MUnHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>? M3;yOVExKM7:TR?= NFXQcWhFVVOR M33mUmVEPTB;MkOyJI5O NFjQdlEyQTB4NEezNC=>
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CEM/C3 NV3KTXhjT3Kxd4ToJIlvcGmkaYTvdpkh[XO|YYm= MoPjNVAh|ryP MlfNSG1UVw>? M3\q[GVEPTB;MkW3JI5O MoC1NVkxPjR5M{C=
CEM/C2 M3XTbmdzd3e2aDDpcohq[mm2b4L5JIF{e2G7 M1HDclExKM7:TR?= NWLJWIpCTE2VTx?= M3\ofmVEPTB;MkexJI5O M4LMVVE6ODZ2N{Ow
CCRFCEM NV3o[plxT3Kxd4ToJIlvcGmkaYTvdpkh[XO|YYm= NUnkb5FKOTBizszN NVTrfYg5TE2VTx?= M{nMZmVEPTB;M{K3JI5O NYm0UIUzOTlyNkS3N|A>
CEM/C1 M{X1eGdzd3e2aDDpcohq[mm2b4L5JIF{e2G7 M1Lvc|ExKM7:TR?= NEjvWFZFVVOR MofOSWM2OD1|OEKgcm0> M2O3XFE6ODZ2N{Ow
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I 2.1 MVfBdI9xfG:|aYOgZZN{[Xl? Mn\tNVAh|ryP NHL6NFdFVVOR MV3pcoR2[2W|IHHwc5B1d3Orcx?= MnjNNVkxPjR5M{C=
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Rh41 MXHHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>? M{K2PVExKM7:TR?= NHS4UItKSzVyPUOzMlghdk1? MUKyNFc1ODZ{Mx?=
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BT-12 M{HTOWdzd3e2aDDpcohq[mm2b4L5JIF{e2G7 M1GzdFExKM7:TR?= NXXUbYl4UUN3ME6xNEDPxE1? NUHt[VB{OjB5NEC2NlM>
CHLA-266 M4jsfWdzd3e2aDDpcohq[mm2b4L5JIF{e2G7 NE\NfpAyOCEQvF2= MV3JR|UxRTFwMkKg{txO NWTOU4VZOjB5NEC2NlM>
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CHLA-10 MYjHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>? MXmxNEDPxE1? NIDIWFdKSzVyPUGwNkBvVQ>? MUiyNFc1ODZ{Mx?=
CHLA-258 NX;IXHhuT3Kxd4ToJIlvcGmkaYTvdpkh[XO|YYm= MUexNEDPxE1? NFrOXJhKSzVyPUGuNFUh|ryP NI[3bI8zODd2ME[yNy=>
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NB-1643 M4LNXGdzd3e2aDDpcohq[mm2b4L5JIF{e2G7 NYPxT2c4OTBizszN NYDVWllOUUN3ME21MlQh|ryP NUmwfox2OjB5NEC2NlM>
NB-Ebc1 NXrEfI5OT3Kxd4ToJIlvcGmkaYTvdpkh[XO|YYm= NYX1TpVkOTBizszN NFfNc25KSzVyPkGwJO69VQ>? NFnkVZEzODd2ME[yNy=>
CHLA-90 M{D4Nmdzd3e2aDDpcohq[mm2b4L5JIF{e2G7 NFrSb5EyOCEQvF2= NYnNcFB7UUN3ME6xNEDPxE1? NWWzO|NQOjB5NEC2NlM>
CHLA-136 NYr3[YNmT3Kxd4ToJIlvcGmkaYTvdpkh[XO|YYm= NFu2RngyOCEQvF2= NUjWXWNXUUN3ME6xNEDPxE1? NIDsUFgzODd2ME[yNy=>
NALM-6 NHn6VYZIem:5dHigbY5pcWKrdH;yfUBie3OjeR?= M4qyZ|ExKM7:TR?= M{X6UGlEPTB;Mk[1JI5O NGXBW3kzODd2ME[yNy=>
COG-LL-317 M1nXfWdzd3e2aDDpcohq[mm2b4L5JIF{e2G7 MlLLNVAh|ryP MVnJR|UxRTZwNEmgcm0> MUOyNFc1ODZ{Mx?=
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MOLT-4 NFLLTnhIem:5dHigbY5pcWKrdH;yfUBie3OjeR?= NH3M[owyOCEQvF2= MmrKTWM2OD12MDDuUS=> NHPjSW0zODd2ME[yNy=>
CCRF-CEM NWPybFNjT3Kxd4ToJIlvcGmkaYTvdpkh[XO|YYm= MVKxNEDPxE1? NFnBd5VKSzVyPUK2PEBvVQ>? MoLXNlA4PDB4MkO=
Kasumi-1 MUnHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>? MmTFNVAh|ryP MVPJR|UxRTFyNzDuUS=> MVqyNFc1ODZ{Mx?=
Karpas-299 MnzPS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl? M4[xUlExKM7:TR?= M37VTWlEPTB;Mj65N{DPxE1? MXmyNFc1ODZ{Mx?=
Ramos-RA1 NFqzcoxIem:5dHigbY5pcWKrdH;yfUBie3OjeR?= M2TyeVExKM7:TR?= MUXJR|UxRTdwM{Wg{txO NEn2[oIzODd2ME[yNy=>
H1299 NYS3SVAzU2mwYYPlJIF{e2G7 MXqxNEDPxE1? MULpcohq[mm2czDJT2JMTS2rbnT1Z4VlKEGtdDDBZ5RqfmG2aX;u NXLpZ4lIOjF7MEi2NVY>
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)

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
2 years -80°C in solvent
Smiles C1CC2=C3C(=CC=C2)C(=CN3C1)C4C(C(=O)NC4=O)C5=CNC6=CC=CC=C65

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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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