4-Pyridylanilinothiazoles that selectively target von Hippel-Lindau deficient renal cell carcinoma cells by inducing autophagic cell death.

ABSTRACT: Renal cell carcinomas (RCC) are refractory to standard therapy with advanced RCC having a poor prognosis; consequently treatment of advanced RCC represents an unmet clinical need. The von Hippel-Lindau (VHL) tumor suppressor gene is mutated or inactivated in a majority of RCCs. We recently identified a 4-pyridyl-2-anilinothiazole (PAT) with selective cytotoxicity against VHL-deficient renal cells mediated by induction of autophagy and increased acidification of autolysosomes. We report exploration of structure-activity relationships (SAR) around this PAT lead. Analogues with substituents on each of the three rings, and various linkers between rings, were synthesized and tested in vitro using paired RCC4 cell lines. A contour map describing the relative spatial contributions of different ch

SUBMITTER: Hay MP 

PROVIDER: S-EPMC2838715 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature