Novel Adamantanyl-Based Thiadiazolyl Pyrazoles Targeting EGFR in Triple-Negative Breast Cancer.

ABSTRACT: The epidermal growth factor receptor (EGFR) is a validated therapeutic target for triple-negative breast cancer (TNBC). In the present study, we synthesize novel adamantanyl-based thiadiazolyl pyrazoles by introducing the adamantane ring to thiazolopyrazoline. On the basis of loss of cell viability in TNBC cells, 4-(adamantan-1-yl)-2-(3-(2,4-dichlorophenyl)-5-phenyl-4,5-dihydro-1H-pyrazol-1-yl)thiazole (APP) was identified as a lead compound. Using a Parzen-Rosenblatt Window classifier, APP was predicted to target the EGFR protein, and the same was confirmed by surface plasmon resonance. Further analysis revealed that APP suppressed the phosphorylation of EGFR at Y992, Y1045, Y1068, Y1086, Y1148, and Y1173 in TNBC cells. APP also inhibited the phosphorylation of ERK at Y204 and of S

SUBMITTER: Sebastian A 

PROVIDER: S-EPMC6044684 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature