Crenolanib is a potent and selective inhibitor of PDGFRα/β, FLT3 with Kd of 2.1 nM/3.2 nM, 0.74 nM, respectively, sensitive to D842V mutation not V561D mutation, and > 100-fold more selective for PDGFR than c-Kit, VEGFR-2, TIE-2, FGFR-2, EGFR, erbB2, and Src.
CAS Number: 670220-88-9
Molecular Weight: 443.54
Chemical Name: 1-(2-(5-((3-methyloxetan-3-yl)methoxy)-1H-benzo[d]imidazol-1-yl)quinolin-8-yl)piperidin-4-amine.
Appearance: Solid Power
Purity: ≥98% (or refer to the Certificate of Analysis)
Solubility: 10 mM in DMSO
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis
Storage Condition: Dry, dark and -20 oC for 1 year or refer to the Certificate of Analysis.
Shelf Life: ≥12 months if stored properly.
Stock Solution Storage: 0 - 4 oC for 1 month or refer to the Certificate of Analysis.
Drug Formulation: To be determined.
HS Tariff Code: 382200
How to use
Crenolanib has 25-fold more affinity for PDGFRA/B compared with KIT, and is approximately 135-fold more potent than imatinib for inhibiting the PDGFRA D842V mutation. The IC50 for crenolanib for a KIT exon 11 deletion mutant kinase is greater than 1, 000 versus 8 nM for imatinib. Crenolanib has low nanomolar potency against the V561D + D842V-mutant kinase that is similar to its potency against the isolated D842V mutation. Both imatinib and crenolanib potently inhibit the kinase activity of the fusion oncogene with IC50 values of 1 and 21 nM, respectively, and inhibits PDGFRA activation in this cell line with IC50 values of 93 and 26 nM, respectively. HL60/VCR and K562/ABCB1 cells, overexpressing ABCB1, are 6.9- and 3.6-fold resistant to crenolanib, respectively, in relation to parental HL60 and K562 cells. PSC-833 fully reverses resistance to crenolanib in both HL60/VCR and K562/ABCB1 cells. Crenolanib (1 nM-10 μM) stimulates ABCB1 ATPase activity in a concentration-dependent manner. Crenolanib treatment does not increase the cell surface expression of ABCB1. Crenolanib inhibits [125I]-IAAP photocrosslinking of ABCB1 at high concentrations, with 50 % inhibition at 10 μM, but has little effect at lower concentrations, below 1 μM. Crenolanib decreases NSCLC cell viability, induces apoptosis in NSCLC cells, and inhibits cell migration in NSCLC cells.
Crenolanib (10 mg/kg and 20 mg/kg) suppresses non-small-cell lung cancer tumor growth in vivo and induces tumor cell apoptosis, and the dosage of crenolanib applied is well tolerated by recipient mice.
- Heinrich MC, et al.Crenolanib inhibits the drug-resistant PDGFRA D842V mutation associated with imatinib-resistant gastrointestinal stromal tumors. Clin Cancer Res, 2012, Jun 27.
- Mathias TJ, et al. The FLT3 and PDGFR inhibitor crenolanib is a substrate of the multidrug resistance protein ABCB1 but does not inhibit transport function at pharmacologically relevant concentrations. Invest New Drugs. 2015 Apr;33(2):300-9.
- Wang P, et al. Crenolanib, a PDGFR inhibitor, suppresses lung cancer cell proliferation and inhibits tumor growth in vivo. Onco Targets Ther. 2014 Sep 26;7:1761-8.
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