BIIB068 is a potent, selective, reversible and orally active BTK inhibitor with an IC50 of 1 nM and a Kd of 0.3 nM. BIIB068 shows more >400-fold selective for BTK than other kinases. BIIB068 has the potential for autoimmune diseases research.
IC50&Target
IC50: 1 nM (BTK)
Kd: 0.3 nM (BTK)
体外研究
BIIB068 (compound 1) improves the whole blood cell potency (human whole blood BTK phosphorylation (IC50 = 0.12 µM).
BIIB068 (compound 1; 30 µM,10 µM, 3.3 µM, and 1.1 µM) inhibits BCR mediated PLCγ2 phosphorylation in Ramos B cells (IC50= 0.4 µM), anti-IgD induced and anti-IgM BCR-induced B cell activation in human PBMCs (IC50 = 0.11 µM and 0.21 µM, respectively).
BIIB068 (compound 1) inhibits FcγR-mediated ROS production in neutrophils with an IC50 of 54 nM.
体内研究
BIIB068 (compound 1) is stable in the plasma of mouse, rat, beagle dog, and cynomolgus monkey (>95% parent compound remaining after 6 hours of incubation).
BIIB068 (compound 1) exhibits good drug-like properties (LLE = 5) which results in low in vivo clearance (CL %Qh = 6) and moderate oral bioavailability (%F = 48) when dosed in rats. BIIB068 (5 mg/kg; po) treatment shows the T1/2 of 1.2 hours, 2.1 hours and 0.9 hour for rats, dog and cynomolgus monkey, respectively. BIIB068 shows acceptable ADME (absorption, distribution, metabolism, and excretion) properties.
分子式
C23H29N7O2
分子量
435.52
CAS号
1798787-27-5
运输条件
Room temperature in continental US; may vary elsewhere.