NVP-BVB808

NVP-BVB808 is a selective and ATP-competitive JAK2 inhibitor with an IC₅₀ of 0.35 nM. NVP-BVB808 binds to JAK2’s ATP-binding site, stabilizes JAK2’s active conformation, increases JAK2 activation loop phosphorylation, and blocks downstream kinase function. NVP-BVB808 exhibits antiproliferative and pro-apoptosis effects, suppresses constitutive STAT5a phosphorylation. NVP-BVB808 can be used for the research of cancer, such as leukemia^[1]. In Vitro:NVP-BVB808 (11 individual concentrations; 72 h) potently inhibits proliferation of JAK2-mutant CHRF-288-11, SET-2, and UKE-1 cells with GI₅₀ values of 0.15 μM, 0.25 μM, and 0.22 μM respectively after 72 hours, shows weaker activity against HEL cells (GI₅₀ = 2.13 μM), and inhibits proliferation of BCR-ABL-positive and JAK2 wild-type cell lines only at higher concentrations (GI₅₀ = 0.73-3.20 μM)^[1].
NVP-BVB808 (72 h) induces apoptosis in CHRF-288-11, SET-2, HEL, Lama-87, KU-812, BV173, K562, and KCL-22 cells, with the highest potency against CHRF-288-11 cells (IC₅₀ = 0.3 μM) and decreasing potency across the remaining cell lines^[1].
NVP-BVB808 (0-1 μM; 30 min) potently inhibits STAT5a phosphorylation in JAK2-mutant SET-2, and HEL cells at concentrations as low as 0.05 μM after 30 minutes, while showing minimal effect on BCR-ABL-positive K562 and KCL-22 cells^[1].