Asciminib hydrochloride

SKU: orb1940871

Description

Asciminib (ABL001) hydrochloride binds to the myristoyl pocket of ABL1 and induces the formation of an inactive kinase conformation.Asciminib hydrochloride binds potently (dissociation constant=0.5-0.8 nM) and selectively to the myristoyl pocket of ABL1 and induces the inactive C-terminal helix conformation. Asciminib hydrochloride exhibits the same non-ATP-competitive biochemical kinetics as the BCR–ABL inhibitor GNF-2 but with approximately 100-fold greater potency.Asciminib hydrochloride lacks activity against more than 60 kinases, including SRC, and is similarly inactive against G-protein-coupled receptors, ion channels, nuclear receptors and transporters.

Key Properties

• CAS Number: 2119669-71-3
• MW: 486.3
• Purity: >98% (HPLC)
• Formula: C₂₀H₁₉Cl₂F₂N₅O₃
• SMILES: O=C(NC1=CC=C(C=C1)OC(Cl)(F)F)C2=CC(C3=NNC=C3)=C(N=C2)N4C[C@@H](CC4)O.[H]Cl
• Target: Bcr-Abl
• Solubility: DMSO : 100 mg/mL (205.63 mM; Need ultrasonic);H2O : < 0.1 mg/mL (ultrasonic) (insoluble)

Bioactivity

• In Vivo:
  Single doses of 7.5, 15 and 30 mg/kg Asciminib, administered to mice bearing KCL-22 xenografts, inhibits pSTAT5 (Tyr694), which return to baseline at 10, 12 and 16-20 h after administration of the dose, respectively. In mice implanted with KCL-22 tumors, the minimum dose of Asciminib required for complete regression is 7.5 mg/kg twice a day (BID) or 30 mg/kg once a day (QD), and is tolerated at doses up to 250 mg/kg BID.
• In Vitro:
  Asciminib (ABL001) hydrochloride binds to the myristoyl pocket of ABL1 and induces the formation of an inactive kinase conformation. Asciminib hydrochloride binds potently (dissociation constant=0.5-0.8 nM) and selectively to the myristoyl pocket of ABL1 and induces the inactive C-terminal helix conformation. Asciminib hydrochloride exhibits the same non-ATP-competitive biochemical kinetics as the BCR-ABL inhibitor GNF-2 but with approximately 100-fold greater potency. Asciminib hydrochloride lacks activity against more than 60 kinases, including SRC, and is similarly inactive against G-protein-coupled receptors, ion channels, nuclear receptors and transporters. In BCR-ABL1-transformed Ba/F3 cells grown without IL-3, Asciminib hydrochloride has an anti-proliferative with IC50 value of 0.25 nM. In the CML blast-phase cell line KCL-22, Asciminib hydrochloride inhibits phosphorylation of both STAT5 (Tyr694; pSTAT5) and BCR-ABL1 (Tyr245; pBCR-ABL1) after 1 h using concentrations that correlate with those required for inhibition of cell proliferation. Asciminib hydrochloride is selectively active against all BCR-ABL1 lines (IC50 value of 1-20 nM), irrespective of the presence of either the p210 or the p190 BCR-ABL1 isoform.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Quick Database Links

Gene Symbol

Bcr-Abl