Characteristics
SAR131675 is a potent and selective VEGFR-3 tyrosine kinase inhibitor
Biological Activity
sar131675 is a selective inhibitor of vegfr-3 with ic50 value of 20nm [1].sar131675 is an atp-competitive inhibitor. it inhibits recombinant human vegfr-3 with ic50 value of 23nm and inhibits the kinase activity of vegfr-3 with ki value of 12nm. sar131675 is found to be cell permeable and inhibits vegfr-3 autophosphorylation in hek cells with ic50 values ranging from 30nm to 50nm. sar131675 shows ic50 values of >3μm and 235nm against vegfr-1 and vegfr-2, respectively. it also havs no inhibitory effect on a panel of 65 kinases, 107 nonkinase enzymes and receptors and on 21 ion channels. moreover, sar131675 inhibits lymphatic cell survival induced by vegfc and vegfd with ic50 values of 14nm and 17nm. on another hand, sar131675 exerts inhibition of the migration induced by vegfa or vegfc with ic50 values of 100nm and <30nm in hlmvec cells, respectively [1]..
in vitro
SAR131675 inhibits the proliferation of primary human lymph node cells induced by VEGFR-3 ligands VEGFC and VEGFD in a dose-dependent manner with IC50 of approximately 20 nM, and also inhibits the activity of rh-VEGFR-3–TK in a dose-dependent manner characteristic, IC50 of 23 nM. SAR131675 inhibits VEGFR-1–TK activity with IC50 greater than 3 μM and inhibits VEGFR-2–TK activity with IC50 of 235 nM.
in vivo
sar131675 abrogates lymphangiogenesis and angiogenesis induced by fgf2. it also shows antitumor activity in the mice models. treatment with sar131675 significantly reduces the tumor volume of 4t1 mammary carcinoma tumors [1]
References
[1] alam a, blanc i, gueguen-dorbes g, et al. sar131675, a potent and selective vegfr-3–tk inhibitor with antilymphangiogenic, antitumoral, and antimetastatic activities. molecular cancer therapeutics, 2012, 11(8): 1637-1649.
