BMS-935177是有效，选择性，可逆的布鲁顿酪氨酸激酶(Btk)抑制剂，IC50值为3nM。
CAS：1231889-53-4
分子式：C31H26N4O3
分子量：502.56
纯度：98%
存储：Store at -20°C

Background:

BMS-935177 is a potent and selective reversible inhibitor of Bruton’s tyrosine kinase (Btk) with an IC50 of 3 nM.

In B cells stimulated through the BCR, BMS-935177 selectively inhibits several different readouts. BMS-935177 inhibits calcium flux in human Ramos B cells (IC50=27 nM) and inhibits CD69 surface expression in peripheral B cells stimulated with antiIgM and anti-IgG. However, BMS-935177 has no effect on CD69 surface expression in B cells stimulated through the CD40 receptor with CD40 ligand. Against IgG-containing immune complexdriven low affinity activating Fcγ receptor (FcγRIIa and FcγRIII) end points in peripheral blood mononuclear cells (PBMCs), BMS-935177 effectively inhibits TNFα production with an IC50 value of 14 nM. BMS-935177 shows mean IC50 values of 550±100 (n=11) and 2060±240 nM (n=3) in human and mouse whole blood, respectively[1].

When dosed orally once daily at 5, 20, and 45 mg/kg to mice, BMS-935177 inhibits anti-KLH antibodies of the IgG isotype at day 14, with statistically significant reductions at all doses. In satellite mice from this study dosed with 6 at 5 mg/kg, the plasma concentration is maintained above the mouse whole blood BCR-stimulated CD69 IC50 value of 2 μM for only approximately 5 h. At once daily oral doses of 10, 20, and 30 mg/kg beginning on the day of primary immunization, BMS-935177 provides a clear dose-dependent reduction in both the severity and incidence of clinically evident disease in this rodent model of RA. At 10 mg/kg of BMS-935177, disease severity is reduced about 40% compared to vehicle treatment, and the percentage of animals showing any signs of disease is reduced by a third[1].

[1]. De Lucca GV, et al. Small Molecule Reversible Inhibitors of Bruton’s Tyrosine Kinase (BTK): Structure-Activity Relationships Leading to the Identification of 7-(2-Hydroxypropan-2-yl)-4-[2-methyl-3-(4-oxo-3,4-dihydroquinazolin-3-yl)phenyl]-9H-carbazole-1-carboxamide (BMS-935177). J Med Chem. 2016 Sep 8;59(17):7915-35.