EAI045

Research use only, not for human use.

EAI045, an allosteric inhibitor, targets towards drug-resistant EGFR mutants but avoids the wild-type receptor.

EAI045 ia a potent and selective EGFR inhbitor. EAI045 targets selected drug-resistant EGFR mutants but spares the wild-type receptor. EAI045 inhibits L858R/T790M-mutant EGFR with low-nanomolar potency in biochemical assays.

EAI045 potently inhibits EGFR Y1173 phosphorylation in H1975 cells (EC50=2 nM), but not in HaCaT cells. EAI045 is an inhibitor of the L858R/T790M mutant with 1000-fold selectivity versus wild type EGFR at 1 mM ATP. Profiling of EAI045 against a panel of 250 protein kinases reveals exquisite selectivity; no other kinases are inhibited by more than 20% at 1 μM EAI045. EAI045 has high potency and selectivity for L858R/T790M mutation. In L858R/T790M-mutant NSCLC cell line H1975 cells, EAI045 decreases but does not completely abolish the EGFR autophosphorylation. In stably transfected NIH-3T3 cells harboring the L858R/T790M EGFR mutant, EAI045 shows the same activity. In L858R-mutant H3255 cells, EAI045 exhibits moderate activity. In the HaCaT cells, a keratinocyte cell line with wild-type EGFR, EAI045 does not show any activity of inhibiting EGFR phosphorylation. It confirms the selectivity of EAI045 for mutant EGFR.

In a genetically engineered mouse model of L858R/T790Mmutant-driven lung cancer , remarkable tumor regression is observed in L858R/T790M-mutant mice treated with the combination of EAI045 and cetuximab. No response is seen in those mice treated with EAI045 alone. The same effect is seen in both L858R/T790M/C797S- engineered Ba/F3 cells and in mice carrying the L858R/T790M/C797S tumor xenografts. These assays clearly show that EAI045 can overcome resistance from acquired T790M and C797S mutations.

EAI045 | EAI-045 | EAI 045

MAPK/ERK Signaling

p38 MAPK

EGFR mutants

Cancer

——

1942114-09-1

383.4

C19H14FN3O3S

>98% (HPLC)

DMSO : ≥ 28 mg/mL; 73.03 mM

c1ccc2c(c1)CN(C2=O)C(C(=O)Nc1sccn1)c1cc(ccc1O)F

2-(5-fluoro-2-hydroxyphenyl)-2-(3-oxo-1H-isoindol-2-yl)-N-(1,3-thiazol-2-yl)acetamide

(-20℃)

With Ice Pack

≥ 2 years