ABL-001

• CAT Number: I002918
• CAS Number: 1492952-76-7
• Molecular Formula: C₂₀H₁₈ClF₂N₅O₃
• Molecular Weight: 449.84
• Purity: ≥95%
• Target: BCR-ABL inhibitor
• Solubility: Soluble in DMSO, not in water
• Storage: 0 - 4°Cfor short term (days to weeks), or -20 °C for long term (months).
• InChI: InChI=1S/C20H18ClF2N5O3/c21-20(22,23)31-15-3-1-13(2-4-15)26-19(30)12-9-16(17-5-7-25-27-17)18(24-10-12)28-8-6-14(29)11-28/h1-5,7,9-10,14,29H,6,8,11H2,(H,25,27)(H,26,30)/t14-/m1/s1
• InChIKey: VOVZXURTCKPRDQ-CQSZACIVSA-N
• SMILES: C1CN(CC1O)C2=NC=C(C=C2C3=CC=NN3)C(=O)NC4=CC=C(C=C4)OC(F)(F)Cl

Asciminib, also known as ABL001, is a potent allosteric inhibitor of BCR-ABL. ABL001 prevents emergence of resistant disease when administered in combination with nilotinib in an in vivo murine model of chronic myeloid leukemia. Cell proliferation studies demonstrate that ABL001 selectively inhibited the growth of CML and Ph+ ALL cells with potencies ranging from 1-10nM range. ABL001 was tested for activity against clinically observed mutations and found to be active in the low nM range. In the KCL-22 mouse xenograft model, ABL001 displayed potent anti-tumor activity with complete tumor regression observed and a clear dose-dependent correlation with pSTAT5 inhibition.

Reference

1:Wylie AA, Schoepfer J, Jahnke W, Cowan-Jacob SW, Loo A, Furet P, Marzinzik AL, Pelle X, Donovan J, Zhu W, Buonamici S, Hassan AQ, Lombardo F, Iyer V, Palmer M, Berellini G, Dodd S, Thohan S, Bitter H, Branford S, Ross DM, Hughes TP, Petruzzelli L, Vanasse KG, Warmuth M, Hofmann F, Keen NJ, Sellers WR.The allosteric inhibitor ABL001 enables dual targeting of BCR-ABL1.Nature. 2017 Mar 30;543(7647):733-737. doi: 10.1038/nature21702.PMID: 28329763