EGFR-IN-11

EGFR-IN-11 is a selective inhibitor of EGFR-tyrosine kinase and induces cell apoptosis. EGFR-IN-11 inhibits triple mutant EGFRL858R/T790M/C797S with an IC50 of 18 nM and arrests cell cycle at G0/G1.

EGFR HER2-IN-11 (compound 20), an orally active dual inhibitor targeting human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR), demonstrates IC50 values of 7.7 nM and 22 nM, respectively. This compound shows strong antitumor efficacy, specifically inhibiting the proliferation of BT-474 cancer cells with a GI50 of 601 nM [1].

MS 154 is a potent and selective cereblon-recruiting Degrader (PROTAC®) of mutant epidermal growth factor receptor (EGFR), comprising a cereblon-binding moiety joined by a linker to gefitinib(Iressa). MS 154 decreases EGFR protein levels, inhibits downstream signaling in and inhibits proliferation of mutant EGFR-bearing lung cancer cells (DC50values are 11 and 25 nM in HCC-827 and H3255 cells, respectively; Dmax> 95% at 50 nM), but not in WT-EGFR-bearing ovarian and lung cancer cells lines. Bioavailable in mice following ip administration.

HSP90-IN-11 is a potent inhibitor of HSP90 and induces significant accumulation of the sub-G1 population. HSP90-IN-11 has a potent HSP90α inhibitory effect comparable to that of AUY-922 (Luminespib). In CRC and NSCLC cells, HSP90-IN-11 exhibited significant anti-proliferative activity in the double-digit nM range.HSP90-IN-11 was able to rapidly degrade client proteins EGFR and Akt in NSCLC cells.

Afatinib impurity 11 is a byproduct of Afatinib, an irreversible EGFR family inhibitor with IC50 values of 0.5 nM, 0.4 nM, 10 nM, and 14 nM for EGFRwt, EGFRL858R, EGFRL858R T790M, and HER2, respectively[1].