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 40 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 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=>
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MDA-MB-468 Mo\3S5Jwf3SqIHnubIljcXSxcomgZZN{[Xl? NITDT20yOCEQvF2= M{LvT2ROW09? Mlf0TWM2OD1|MkC4JI5O MmTKNVg{QDF2NES=
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MDA-MB-231 MVzHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>? NEnzT|IyOCEQvF2= M{PJ[GROW09? MkXtTWM2OD5zMDywNFAhdk1? NVnzZlVDOTh|OEG0OFQ>
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SKOV-3 MXzHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>? NVTTcWdtOTBizszN Mn7qSG1UVw>? NF[xXHpKSzVyPUKxNlYhdk1? M2PVd|E5OzhzNES0
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PANC-1 NHPkRo1Iem:5dHigbY5pcWKrdH;yfUBie3OjeR?= MlTJNVAh|ryP Moq1SG1UVw>? NGDuUI5KSzVyPUi2PFEhdk1? NHfnd5UyQDN6MUS0OC=>
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DU145 NHvxXWdIem:5dHigbY5pcWKrdH;yfUBie3OjeR?= NWnPNllqOTBizszN NV;pXI1QTE2VTx?= M3rrO2lEPTB;M{ixNkBvVQ>? NIfsTIwyQDN6MUS0OC=>
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BT474 NWS4XVl6U2mwYYPlJIF{e2G7 NX7KNZIxOTBizszN M1LyeGROW09? MV\pcohq[mm2czDwS3NMO87{IIfpeIghUUN3MDDv[kAyPjBibl2= MmPMNVg{QDF2NES=
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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
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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=>
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

Solubility (25°C)

In vitro

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

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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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