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 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=>
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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

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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Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

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Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

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

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

Mass Concentration Volume Molecular Weight

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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