ARQ 531 - 98%, high purity , CAS No.2095393-15-8, Inhibitor of BLK proto-oncogene; Src family tyrosine kinase;Inhibitor of BMX non-receptor tyrosine kinase;Inhibitor of Bruton tyrosine kinase;Inhibitor of tec protein tyrosine kinase;Inhibitor of YES proto-oncogene 1; Src family tyrosine kinase

Item Number

A414128

• Synonyms: ARQ 531|2095393-15-8|ARQ-531|nemtabrutinib|JTZ51LIXN4|MK-1026|ARQ531|(2-Chloro-4-phenoxyphenyl)(4-(((3R,6S)-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl)amino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl)methanone|(2-chloro-4-phenoxyphenyl)-[4-[[(3R,6S)-6-(hydroxymethyl
• Specifications & Purity: 98%
• Storage Temp: Store at -20°C
• Shipped In: Ice chest + Ice pads
• Action Type: INHIBITOR
• Mechanism of action: Inhibitor of BLK proto-oncogene; Src family tyrosine kinase;Inhibitor of BMX non-receptor tyrosine kinase;Inhibitor of Bruton tyrosine kinase;Inhibitor of tec protein tyrosine kinase;Inhibitor of YES proto-oncogene 1; Src family tyrosine kinase

Product Description

Information

ARQ 531 ARQ 531 is an ATP-competitive tyrosine kinase inhibitor designed to target BTK with an IC50 of 0.85 nM. It also has a distinct kinase selectivity profile with strong inhibitory activity against several key oncogenic drivers from TEC, Trk and Src family kinases.

Targets

BTK (Cell-free assay); BRK (Cell-dree); BRK (Cell-free assay); LCK (Cell-free); LCK (Cell-free assay) 29927,0.85 nM; 2.45 nM; 2.45 nM; 3.86 nM; 3.86 nM

In vitro

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.

In vivo

ARQ 531 has potent anti-tumor activity was observed in both ABC-DLBCL and GCB-DLBCL mouse xenograft models. 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.

Cell Research(from reference)

Cell lines：CLL cells 

Concentrations：0.1 μM, 1.0 μM, or 10.0 μM 

Incubation Time：72 h