BIIB068

• CAT Number: I023385
• CAS Number: 1798787-27-5
• Molecular Formula: C23H29N7O2
• Molecular Weight: 435.52
• Purity: ≥95%
• Synonyms: N-[[2-methyl-4-[2-[(1-methylpyrazol-4-yl)amino]pyrimidin-4-yl]phenyl]methyl]-3-propan-2-yloxyazetidine-1-carboxamide
• InChI: InChI=1S/C23H29N7O2/c1-15(2)32-20-13-30(14-20)23(31)25-10-18-6-5-17(9-16(18)3)21-7-8-24-22(28-21)27-19-11-26-29(4)12-19/h5-9,11-12,15,20H,10,13-14H2,1-4H3,(H,25,31)(H,24,27,28)
• InChIKey: BMWMKGNVAMXXCH-UHFFFAOYSA-N
• SMILES: CC1=C(C=CC(=C1)C2=NC(=NC=C2)NC3=CN(N=C3)C)CNC(=O)N4CC(C4)OC(C)C

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[1].
BIIB068 (compound 1) improves the whole blood cell potency (human whole blood BTK phosphorylation (IC50 = 0.12 µM)[1].
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)[1].
BIIB068 (compound 1) inhibits FcγR-mediated ROS production in neutrophils with an IC50 of 54 nM[1].
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)[1].
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[1].

Reference

[1]. Bin Ma, Tonika Bohnert, et al. Discovery of BIIB068: A Selective, Potent, Reversible Bruton’s Tyrosine Kinase Inhibitor as an Orally Efficacious Agent for Autoimmune Diseases. J Med Chem. 2020 Jul 22.
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