Uses
BMS 935177 is a potent and selective reversible inhibitor of Bruton’s tyrosine kinase (Btk) with an IC50 of 3 nM.
Biological Activity
BMS-935177 is a potent and reversible BTK inhibitor with IC50 of 2.8 nM and good kinase selectivity. It is more potent and 5-67 times more selective against BTK than other kinases such as TEC, BMX, ITK, and TXK.
in vitro
BMS-935177 is more than 50-fold selective for BTK over SRC kinase family members. In Ramos B cells, it inhibits calcium flux; in peripheral blood B lymphocytes stimulated with anti-IgM and anti-IgG, it inhibits the cell surface expression of CD69. However, BMS-935177 had no effect on CD69 expression in B cells stimulated by CD40 receptor and ligand. In PBMCs, it can effectively inhibit the production of TNF-α with IC50 of 14 nM.
in vivo
Among the various tested species, BMS-935177 is highly bound to plasma proteins, with a free drug ratio of less than 1% in humans. In preclinical tests, it had good oral activity whether administered as a suspension or solution, despite its poor water solubility. When administered in solution, it has an oral bioavailability of 84%-100% in rats, mice, dogs, and cynomolgus monkeys, while in a single intravenous administration experiment, it has a lower in vivo bioavailability clearance rate. The T
1/2 of it was 4 h and 5.1 h by intravenous injection in mice and rats at a dose of 2 mg/kg, respectively.
target
| Target | Value |
BTK
(Cell-free assay) | 2.8 nM |
TEC
(Cell-free assay) | 13 nM |
< td style="border-bottom: 1px dotted #ccc;padding: 5px;"> BLK
(Cell-free assay) 20 nM |
BMX
(Cell-free assay) | 24 nM |
TrkA
(Cell-free assay) | 30 nM |
