BIIB091 是一种有效，选择性，具有口服活性和可逆的 BTK 抑制剂，IC₅₀ 值 <0.5 nM。BIIB091 与 BTK 蛋白结合，将 Tyr-551 隔离成具有出色亲和力的非活性构象。 BIIB091 可用于多发性硬化症的研究。

BIIB091 is a potent, selective, orally active and reversible BTK inhibitor, with an IC 50 of <0.5 nM. BIIB091 binds the BTK protein to sequester TYR-551 into an inactive conformation with excellent affinity. BIIB091 can be used for the research of multiple sclerosis.

Solid

BIIB091 inhibits the phosphorylation of PLCγ2 in the Ramos human B-cell line, with an IC50 of 6.9 nM.
BIIB091 blocks anti-IgM-stimulated CD69 activation in PBMCs with an IC50 of 6.9 nM.
BIIB091 inhibits FcγR-induced ROS production in purified primary neutrophils, with an IC50 of 4.5 nM.
BIIB091 inhibits FcγRI and FcγRIII-mediated TNFα secretion upon simulation with FcγR agonists such as coated human IgG (all FcγR, IC50=5.6 nM), anti-CD16 (FcγRIII, IC50=8.0 nM), anti-CD64 (FcγRI IC50=3.1 nM), and cross-linked anti-CD16 (FcγRIII IC50=1.3 nM) in human monocytes.
BIIB091 inhibits the phosphorylation of BTK (IC50=24 nM) and blocks both BCR mediated B cell and FcεR-induced basophil activation as measured by inhibition of CD69 and CD63 expression (IC50=71 nM and IC5

BIIB091 (0.03-30 mg/kg; p.o. twice daily for 10 d) reduces the anti-NP IgM antibody titers (88%, 77%, 59%, 59%, 44%, 34%, and 22%) in the TI-2 immunization model.

Pharmacokinetics of BIIB091 in preclinical species

species IV (1 mg/kg) PO (5 mg/kg) in HMPC/Tween

Room temperature in continental US; may vary elsewhere.

Powder -20°C 3 years；4°C 2 years

[1]. Hopkins BT, et al. Discovery and Preclinical Characterization of BIIB091, a Reversible, Selective BTK Inhibitor for the Treatment of Multiple Sclerosis. J Med Chem. 2021 Nov 4.

In Vitro: DMSO : 125 mg/mL (230.36 mM; Need ultrasonic)配制储备液