| Bioactivity | BIIB091 is a potent, selective, orally active and reversible BTK inhibitor, with an IC50 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[1]. | ||||||||||||
| Invitro | BIIB091 inhibits the phosphorylation of PLCγ2 in the Ramos human B-cell line, with an IC50 of 6.9 nM[1].BIIB091 blocks anti-IgM-stimulated CD69 activation in PBMCs with an IC50 of 6.9 nM[1].BIIB091 inhibits FcγR-induced ROS production in purified primary neutrophils, with an IC50 of 4.5 nM[1].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[1].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 IC50=82 nM, respectively) in the whole blood assays[1]. | ||||||||||||
| In Vivo | 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[1].Pharmacokinetics of BIIB091 in preclinical species[1]species | ||||||||||||
| Name | BIIB091 | ||||||||||||
| CAS | 2247614-80-6 | ||||||||||||
| Formula | C28H34N10O2 | ||||||||||||
| Molar Mass | 542.64 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
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| Reference | [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. |