BGB-8035

BGB-8035 is an orally active, highly selective bruton's tyrosine kinase (BTK) inhibitor with IC50s of 1.1 nM, 99 nM, 621 nM for BTK, TEC, EGFR, respectively. BGB-8035 has antitumor and anti-arthritis activity. BGB-8035 has the potential for B-cell malignancies and autoimmune diseases research[1].

Research Areas >> Cancer

Research Areas >> Inflammation/Immunology

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> Btk

IC50: 1.1 nM (BTK), 99 nM (TEC), and 621 nM (EGFR)[1]

BGB-8035 对 HEK293 和 Ramos 细胞基本无毒 (IC50>10 μM)[1]。

BGB-8035 (7.5, 15, 30 mg/kg; 灌胃给药; 每天两次; 16 天) 表现出剂量依赖性抗肿瘤活性[1]。 BGB-8035 (1, 3, 10, 30 mg/kg; 灌胃给药; 每天两次; 13 天) 在 8-9 周大的 Lewis 大鼠CIA 模型中以剂量依赖的方式抑制关节炎，并防止 CIA 模型相关的体重减轻[1]。 Pharmacokinetic Parameters of BGB-8035 in Rats and Dogs[1]. Rats (IV; 1 mg/kg) Rats (PO; 5 mg/kg) Dogs (IV; 1 mg/kg) Dogs (PO; 2.5 mg/kg) T1/2 (h) 1.0 2.5 CL (mL/min/kg) 24.4 6.89 Vss (L/kg) 0.9 0.74 Tmax (h) 0.25 0.42 Cmax (ng/mL) 667 1246 AUCinf (h∗ng/mL) 964 2645 F (%) 26.4 43 Animal Model: Female NOD/SCID mice at 9 weeks of age with REC-1 MCL xenografts[1] Dosage: 7.5, 15, 30 mg/kg Administration: PO; BID; 16 days Result: Demonstrated dose-dependent antitumor activity, with TGI values of 64.1, 73.6, and 79.9%, respectively.

[1]. Yunhang Guo, et al. Discovery of BGB-8035, a Highly Selective Covalent Inhibitor of Bruton's Tyrosine Kinase for B-Cell Malignancies and Autoimmune Diseases. J Med Chem. 2023 Mar 23;66(6):4025-4044.