ARQ-531 (ARQ531) is a potent, reversible, orally available inhibitor of both wild type and C481S-mutant BTK kinase with IC50 of 0.85 and 0.39 nM, respectively; also ptently inhibits 45 kinases with >50% inhibition at 200 nM (TEC, BMX, LCK, TRK family kinases etc.); does not require the C481S residue to bind to BTK, inhibits CD69 expression on CD20+ B-cells with IC50 of 42 nM (Ibrutinib, IC50=3 nM); ARQ-531 inhibits proliferation of malignant cells both sensitive and resistant to ibrutinib (SUDHL6 Cell GI50=80 nM), ARQ 531 is superior to Ibrutinib in a TCL1 highly predictive adoptive transfer model of CLL.

>98%

Store at -20℃ for one year（Powder）；Store at 2-4℃ for two weeks；Store at -20℃ for six months after dissolution.

MK-1026

solid powder

DMSO : ≥ 50 mg/mL (104.40 mM)

BTK,BRK,LCK

ARQ 531 potently inhibited BTK (IC50 = 0.85 nM), the binding potency was accompanied by long residence time (51 min). ARQ 531 selectively inhibits BCR signaling dependent PI3K/AKT/mTOR, Ras/Raf/Erk and Rap-GTPase-Cofilin pathways in TMD8 cells. It potently inhibits proliferation of hematological malignant cell lines both sensitive and resistant to ibrutinib addicted to BCR signaling. Unlike ibrutinib, ARQ 531 suppressed both the upstream activating signals (via inhibition of a select member of Src kinase family) and the downstream signaling pathways (via pAKT and pERK kinases). In GCB-DLBCL cell lines (SUDHL-4 and DOHH-2), ARQ 531 potently suppressed expression of anti-apoptotic c-Myc and BCL6 oncoproteins in a dose dependent fashion, and concomitantly induced apoptotic cleavage of PARP protein.

ARQ 531 has potent anti-tumor activity was observed in both ABC-DLBCL and GCB-DLBCL mouse xenograft models[1]. ARQ 531 crosses the blood, brain-barrier. In a single oral dose study of 10mg/kg in monkeys, the bioavailability of ARQ 531 is 72.4% with a Cmax of 9 μM and a half-life greater than 24 hours.