ARQ 531

2095393-15-8

C25H23ClN4O4

DMSO : >= 50 mg/mL (104.40 mM)

Protein Tyrosine Kinase/RTK

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. IC50 & Target: IC50: 0.85 nM (WT-BTK), 0.39 nM (C481S-BTK)^[1]. In Vitro: 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. In Vivo: 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].