Capmatinib hydrochlorideProduct ingredient for Capmatinib

Name
Capmatinib hydrochloride
Drug Entry
Capmatinib

Capmatinib is a small molecule kinase inhibitor targeted against c-Met (a.k.a. hepatocyte growth factor receptor [HGFR]), a receptor tyrosine kinase that, in healthy humans, activates signaling cascades involved in organ regeneration and tissue repair.2 Aberrant c-Met activation - via mutations, amplification, and/or overexpression - is known to occur in many types of cancer, and leads to overactivation of multiple downstream signaling pathways such as STAT3, PI3K/ATK, and RAS/MAPK.2 Mutations in MET have been detected in non-small cell lung cancer (NSCLC), and the prevalence of MET amplification in epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI)-naive patients with NSCLC has been reported to be 1.4% - 21%.2 This co-occurrence has made c-Met a desirable target in the treatment of NSCLC.

Manufactured by Novartis and marketed under the brand name Tabrecta, capmatinib was granted accelerated approval by the FDA on May 6, 2020,4 for the treatment of NSCLC in patients whose tumors have a mutation that leads to mesenchymal-epithelial transition (MET) exon 14 skipping.3 The presence of the mutation must be confirmed by an FDA-approved test, such as the FoundationOne CDx assay (manufactured by Foundation Medicine, Inc.), which was approved by the FDA on the same day.4 As this indication was granted under an accelerated approval, its continued approval is contingent upon verification of capmatinib's benefit in confirmatory trials.3 Capmatinib was approved by Health Canada on June 8, 2022.7

Accession Number
DBSALT002950
Structure
Synonyms
Capmatinib dihydrochloride monohydrate / Capmatinib HCl / Capmatinib hydrochloride / Capmatinib hydrochloride hydrate
External IDs
NVP-INC280-AAA
UNII
C2A374O70X
CAS Number
1865733-40-9
Weight
Average: 503.36
Monoisotopic: 502.1087075
Chemical Formula
C23H21Cl2FN6O2
InChI Key
COWBUPJEEDYWKD-UHFFFAOYSA-N
InChI
InChI=1S/C23H17FN6O.2ClH.H2O/c1-25-22(31)18-6-5-16(11-19(18)24)21-13-28-23-27-12-17(30(23)29-21)10-14-4-7-20-15(9-14)3-2-8-26-20;;;/h2-9,11-13H,10H2,1H3,(H,25,31);2*1H;1H2
IUPAC Name
2-fluoro-N-methyl-4-{7-[(quinolin-6-yl)methyl]imidazo[1,2-b][1,2,4]triazin-2-yl}benzamide hydrate dihydrochloride
SMILES
O.Cl.Cl.CNC(=O)C1=C(F)C=C(C=C1)C1=NN2C(CC3=CC4=C(C=C3)N=CC=C4)=CN=C2N=C1
ChemSpider
58791261
ChEMBL
CHEMBL3989937
Wikipedia
Capmatinib
Predicted Properties
PropertyValueSource
Water Solubility0.00529 mg/mLALOGPS
logP3.04ALOGPS
logP2.96Chemaxon
logS-4.9ALOGPS
pKa (Strongest Acidic)12.77Chemaxon
pKa (Strongest Basic)4.55Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count5Chemaxon
Hydrogen Donor Count1Chemaxon
Polar Surface Area85.07 Å2Chemaxon
Rotatable Bond Count4Chemaxon
Refractivity125.27 m3·mol-1Chemaxon
Polarizability42.1 Å3Chemaxon
Number of Rings5Chemaxon
Bioavailability1Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon