Asciminib

SKU: orb1302024

Description

Asciminib (ABL001) is a highly potent and selective allosteric Bcr-Abl inhibitor with sub-nanomolar binding affinity. It is widely used in research for chronic myeloid leukemia (CML), demonstrating efficacy in both cellular assays and in vivo models to study resistance mechanisms and therapeutic strategies.

Research Area

Cardiovascular Research, Signal Transduction

Key Properties

• CAS Number: 1492952-76-7
• MW: 449.84
• Purity: 99.70% (May vary between batches)
• Formula: C₂₀H₁₈ClF₂N₅O₃
• SMILES: C(NC1=CC=C(OC(Cl)(F)F)C=C1)(=O)C2=CC(=C(N=C2)N3CC[C@@H](O)C3)C=4C=CNN4
• Target: Bcr-Abl
• Solubility: H2O:Insoluble;DMSO:245 mg/mL (544.64 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (4.45 mM)

Bioactivity

• Target IC50:
  Abl-1:0.45 nM
• In Vivo:
  Single doses of 7.5, 15 and 30mg kg1 ABL001, administered to mice bearing KCL22 xenografts, inhibited pSTAT5 (Tyr694), which returned to baseline at 10, 12 and 16–20h after administration of the dose, respectively. In mice implanted with KCL-22 tumours, the minimum dose of ABL001 required for complete regression was 7.5mg/kg twice a day (BID) or 30mg/kg once a day (QD), and was tolerated at doses up to 250mg kg1 BID. Similarly, in xenografts derived from patients with Ph+ ALL, treatment with 7.5 and 30mg/kg ABL001 led to regressions that were maintained during dosing .
• In Vitro:
  In Asciminib-transformed Ba/F3 cells grown without IL-3, ABL001 had an anti-proliferative IC50 value of 0.25nM. By contrast, the addition of IL-3 to bypass Asciminib dependence renders these cells insensitive to ABL001. In the CML blast-phase cell line KCL-22, ABL001 inhibited phosphorylation of both STAT5 (Tyr694; pSTAT5) and Asciminib (Tyr245; pAsciminib) after 1h using concentrations that correlate with those required for inhibition of cell proliferation . K562-Dox and K562-ABCG2 cells demonstrated increased LD50 (asciminib) vs K562 control cells: 256 and 299 nM respectively vs 24 nM. Sensitivity was completely restored with specific inhibitors cyclosporine (ABCB1) and Ko143 (ABCG2): K562-Dox LD50 (asciminib+cyclosporine) = 13 nM, K562-ABCG2 LD50 (asciminib+Ko143) = 15 nM .
• Cell Research:
  Cells were resuspended in fresh culture media before culture in 24-well plates in the presence of TKI or asciminib at a density of 2 × 105 cells/mL. Plates were seeded with 1 mL of cell suspension and incubated for 72 h before cell viability determination with 7-aminoactinomycin (7-AAD) and Phycoerythrin (PE)-conjugated Annexin V. Flow cytometric analysis was conducted with a BD LSRFortessa X-20 and FACSDiva software. The lethal dose of asciminib (LD50 asciminib), imatinib (LD50 IM), nilotinib (LD50 NIL) and dasatinib (LD50 DAS) required to cause 50% death of cells was calculated .
• Animal Research:
  Asciminib efficacy in three patient-derived ALL systemic xenograft models (ALL-7015, AL-7119 and AL-7155) is assessed by FACS monitoring of the percentage of CD45+ cells per live cell in blood samples taken at varying time points after dosing with either 7.5 mg/kg BID (group 2) or 30 mg/kg BID (group 3) asciminib for 3 weeks .

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Bcr-Abl, BcrAbl, Asciminib, ABL 001, ABL001, ABL-001, Abl1, inhibit, Inhibitor

Compound Identifiers

PubChem CID

72165228