Pamufetinib (TAS-115) mesylate

InvivoChem Cat #:V4131CAS #:1688673-09-7 Purity >=98%

Description: TAS-115 mesylate is a novel potent inhibitor of VEGFR and hepatocyte growth factor receptor (MET)-targeted kinase with an improved safety profile and with IC50s of 30 and 32 nM for rVEGFR2 and rMET, respectively. VEGF receptor (VEGFR) signaling plays a key role in tumor angiogenesis. Although some VEGFR signal-targeted drugs have been approved for clinical use, their utility is limited by associated toxicities or resistance to such therapy. To overcome these limitations, TAS-115 was developed to inhibit the kinase activity of both VEGFR2 and MET and their signal-dependent cell growth as strongly as other known VEGFR or MET inhibitors. The kinase selectivity of TAS-115 was more specific than that of sunitinib and TAS-115 produced relatively weak inhibition of growth (GI50 > 10 umol/L) in VEGFR signal- or MET signal-independent cells. Furthermore, TAS-115 induced less damage in various normal cells than did other VEGFR inhibitors. These data suggest that TAS-115 is extremely selective and specific, at least in vitro. In in vivo studies, TAS-115 completely suppressed the progression of MET-inactivated tumor by blocking angiogenesis without toxicity when given every day for 6 weeks, even at a serum-saturating dose of TAS-115. The marked selectivity of TAS-115 for kinases and targeted cells was associated with improved tolerability and contributed to the ability to sustain treatment without dose reduction or a washout period. Furthermore, TAS-115 induced marked tumor shrinkage and prolonged survival in MET-amplified human cancer-bearing mice. These data suggest that TAS-115 is a unique VEGFR/MET-targeted inhibitor with improved antitumor efficacy and decreased toxicity. In additoin, it has been reported that the triple inhibition of EGFR, HGF/Met, and VEGF/VEGF receptor 2, by either a triplet of clinical drugs or TAS-115 combined with erlotinib, may be useful for controlling progression of EGFR-mutant lung cancer by reversing EGFR-TKI resistance and for inhibiting angiogenesis.

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References: Mol Cancer Ther. 2013 Dec; 12(12):2685-96; J Thorac Oncol. 2014 Jun; 9(6):775-83.

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Related CAS#: 1190836-34-0 (free base)

-20C for 3 years in powder form

Synonym: TAS115 mesylate; TAS-115; TAS 115;
IUPAC/Chemical Name: 4-(2-fluoro-4-(3-(2-phenylacetyl)thioureido)phenoxy)-7-methoxy-N-methylquinoline-6-carboxamide methanesulfonate
InChi Key: NUYQWFCUOAVQAL-UHFFFAOYSA-N
InChi Code: InChI=1S/C27H23FN4O4S.CH4O3S/c1-29-26(34)19-14-18-21(15-24(19)35-2)30-11-10-22(18)36-23-9-8-17(13-20(23)28)31-27(37)32-25(33)12-16-6-4-3-5-7-16; 1-5(2, 3)4/h3-11, 13-15H, 12H2, 1-2H3, (H, 29, 34)(H2, 31, 32, 33, 37); 1H3, (H, 2, 3, 4)
SMILES Code: O=C(C1=C(OC)C=C2N=CC=C(OC3=CC=C(NC(NC(CC4=CC=CC=C4)=O)=S)C=C3F)C2=C1)NC.OS(=O)(C)=O