| Molecular Formula | C25H23ClN4O4
|
| Molar Mass | 478.93 |
| Density | 1.406±0.06 g/cm3(Predicted) |
| Appearance | Powder |
| pKa | 11.06±0.50(Predicted) |
| Storage Condition | -20℃ |
| Use | ARQ 531 is an ATP-competitive tyrosine kinase inhibitor targeting BTK with an IC50 of 0.85 nM. It has clear kinase selectivity and strong inhibitory activity against several key oncogenic factors such as some family members in TEC, Trk and Src. |
| In vitro study | ARQ 531 effectively inhibited BTK with an IC50 of 0.85 nM and a longer residence time (51 min). In TMD8 cells, ARQ531 selectively inhibits the PI3K/AKT/mTOR, Ras/Raf/Erk and Rap-GTPase-Cofilin signaling pathways that are dependent on BCR signaling. ARQ531 can inhibit the proliferation of BCR signaling-addicted hematologic malignancies cell lines, whether ibrutinib-sensitive or drug-resistant. Unlike ibrutinib, ARQ 531 inhibits upstream activation signals (by inhibiting certain members of the Src kinase family) and downstream signaling pathways (by pAKT and pERK kinases). In GCB-DLBCL cell lines (SUDHL-4 and DOHH-2), ARQ 531 effectively inhibited the expression of anti-apoptotic c-Myc and Bcl6 Oncogene proteins in a concentration-dependent manner while inducing apoptotic cleavage of the PARP protein. |
| In vivo study | ARQ 531 had potent antitumor activity in ABC-DLBCL and GCB-DLBCL mouse xenograft models. ARQ 531 can cross the blood-brain barrier. Monotherapy was administered orally to monkeys at a concentration of 10 mg/kg with an oral availability of 531 for ARQ 72.4%, a Cmax of 9 μm and a half-life of greater than 24 hours. |
