ARQ531是BTK可逆的非共价抑制剂，其对WT-BTK和C481S-BTK的IC50值分别为0.85nM和0.39nM。
CAS：2095393-15-8
分子式：C25H23ClN4O4
分子量：478.93
纯度：98%
存储：Store at -20°C

Background:

ARQ 531 is a reversible non-covalent inhibitor of Bruton’s Tyrosine Kinase (BTK), with IC50s of 0.85 nM and 0.39 nM for WT-BTK and C481S-BTK, respectively.

ARQ 531 shows strong target inhibition in TMD8 cell line. The IC50 values are 0.85 nM and 0.39 nM for WT-BTK and C481S-BTK, respectively, in biochemical assay. Additionally, ARQ 531 also shows strong inhibition of TEK kinases with IC50s of 5.23 nM (BMX), 5.80 nM (TEC), 36.4 nM (TXK). The IC50s of ARQ 531 for SRC kinases are 3.86 nM (LCK), 4.22 nM (YES), 9.71 nM (BLK), 18.3 nM (HCK), 18.8 nM (LYNa), 25.9 nM (FGR), 32.2 nM (FYN), 48.0 nM (FRK) and for TRK kinases are 11.7 nM (TrkB), 13.1 nM (TrkA), 19.1 nM (TrkC). ARQ 531 inhibits proliferation of diverse types of cell lines (TMD8: GI50=1.7 nM, REC1: GI50=0.55 nM) and shows potency in cell lines that are addict to BCR, Src-family kinase and PI3K/AKT pathways.

ARQ 531 is efficacious in TMD-8 tumor xenograft model. ARQ 531 causes complete tumor regression after 14 days of treatment. ARQ 531 is also efficacious in collagen induced arthritis model. ARQ 531 demonstrates potent efficacy against arthritis in mouse model. In the BTK driven TMD8 xenograft mouse model, ARQ 531 demonstrates excellent anti-tumor activity with durable response. ARQ 531 demonstrates in vivo efficacy in a mouse collagen-induced arthritis (CIA) model[1].

[1]. S Eathiraj, et al. Targeting Ibrutinib-Resistant BTK-C481S Mutation with ARQ 531, a Reversible Non-Covalent Inhibitor of BTK. Clinical Lymphoma Myeloma & Leukemia, 2016, 16: S47-S48.