For research use only. Not for therapeutic Use.
CHMFL-EGFR-202 is a potent, irreversible inhibitor of epidermal growth factor receptor (EGFR) mutant kinase, with IC50s of 5.3 nM and 8.3 nM for drug-resistant mutant EGFR T790M and WT EGFR kinases, respectively. CHMFL-EGFR-202 exhibits ～10-fold selectivity for EGFR L858R/T790M against the EGFR wild-type in cells. CHMFL-EGFR-202 adopts a covalent “DFG-in-C-helix-out” inactive binding conformation with EGFR, with strong antiproliferative effects against EGFR mutant-driven nonsmall-cell lung cancer (NSCLC) cell lines[1].
CHMFL-EGFR-202 potently inhibits EGFR primary mutants (L858R, del19) and drug-resistant mutant L858R/T790M[1].
CHMFL-EGFR-202 displays strong binding affinities against wild-type, G719C/S, L858R, L858R/T790M, L861Q, and T790M among EGFR wild-type and mutant kinases[1].
CHMFL-EGFR-202 also exhibits strong binding affinities against BLK, BMX, BTK, ERBB2, ERBB4, LOK, MEK1, and MEK5 kinases (percent of control score less than 1% at 1 μM)[1].
CHMFL-EGFR-202 trongly inhibits BLK, BTK, ERBB2 and ERBB4 with IC50s of 8.1 nM, 24.5 nM, 8.1 nM and 3.2 nM, respectively[1].
CHMFL-EGFR-202 moderately inhibits BMX and MEK1 kinases with IC50 of 111.0 nM and 161.0 nM[1].
| Catalog Number | I018769 |
| CAS Number | 2089381-40-6 |
| Synonyms | 1-[(3R)-3-[4-amino-3-[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]prop-2-en-1-one |
| Molecular Formula | C25H24ClN7O2 |
| Purity | ≥95% |
| InChI | InChI=1S/C25H24ClN7O2/c1-2-21(34)32-11-5-7-18(13-32)33-25-22(24(27)29-15-30-25)23(31-33)16-8-9-20(19(26)12-16)35-14-17-6-3-4-10-28-17/h2-4,6,8-10,12,15,18H,1,5,7,11,13-14H2,(H2,27,29,30)/t18-/m1/s1 |
| InChIKey | RVCKMZIQUFKZFD-GOSISDBHSA-N |
| SMILES | C=CC(=O)N1CCCC(C1)N2C3=NC=NC(=C3C(=N2)C4=CC(=C(C=C4)OCC5=CC=CC=N5)Cl)N |
| Reference | [1]. Wang A, et al. Discovery of (R)-1-(3-(4-Amino-3-(3-chloro-4-(pyridin-2-ylmethoxy)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one (CHMFL-EGFR-202) as a Novel Irreversible EGFR Mutant Kinase Inhibitor with a Distinct Binding Mode. |
