Asciminib hydrochlorideProduct ingredient for Asciminib
- Name
- Asciminib hydrochloride
- Drug Entry
- Asciminib
Asciminib is a tyrosine kinase inhibitor (TKI) used in the treatment of chronic-phase Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML). More specifically, it is an inhibitor of the ABL1 kinase activity of the BCR-ABL1 fusion protein6 which serves as a driver of CML proliferation in most patients with the disease.8 It has also shown benefit in Ph+ CML with the T315I mutation, which produces a mutant BCR-ABL1 which is typically treatment-resistant as compared to wild-type BCR-ABL1.
Existing inhibitors of ABL compete at the ATP binding sites of these proteins and can be classified into those that target the active conformation of the kinase domain (dasatinib, bosutinib) and those that target the inactive kinase domain (imatinib, nilotinib, ponatinib).5 Asciminib is unique in that it acts as an allosteric inhibitor, binding at the myristoyl pocket of the BCR-ABL1 protein and locking it into an inactive conformation.6,3
Asciminib received FDA approval on October 29, 2021 (Scemblix, Novartis AG).7
- Accession Number
- DBSALT003206
- Structure
- Synonyms
- Asciminib HCl / Asciminib hydrochloride
- External IDs
- ABL001-AAA
- UNII
- C5U34S9XFV
- CAS Number
- 2119669-71-3
- Weight
- Average: 486.3
Monoisotopic: 485.0833012 - Chemical Formula
- C20H19Cl2F2N5O3
- InChI Key
- HGCOOPLEWPBLOY-PFEQFJNWSA-N
- InChI
- InChI=1S/C20H18ClF2N5O3.ClH/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);1H/t14-;/m1./s1
- IUPAC Name
- N-[4-(chlorodifluoromethoxy)phenyl]-6-[(3R)-3-hydroxypyrrolidin-1-yl]-5-(1H-pyrazol-3-yl)pyridine-3-carboxamide hydrochloride
- SMILES
- Cl.[H][C@@]1(O)CCN(C1)C1=C(C=C(C=N1)C(=O)NC1=CC=C(OC(F)(F)Cl)C=C1)C1=NNC=C1
- External Links
- ChemSpider
- 81367937
- ChEMBL
- CHEMBL4297220
- Predicted Properties
Property Value Source Water Solubility 0.0554 mg/mL ALOGPS logP 3.08 ALOGPS logP 3.86 Chemaxon logS -3.9 ALOGPS pKa (Strongest Acidic) 14.24 Chemaxon pKa (Strongest Basic) 3.98 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 6 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 103.37 Å2 Chemaxon Rotatable Bond Count 6 Chemaxon Refractivity 104.56 m3·mol-1 Chemaxon Polarizability 43.2 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon