313504-89-1Relevant articles and documents
Tumor-Activated Benzothiazole Inhibitors of Stearoyl-CoA Desaturase
Williams, Noelle S.,Gonzales, Stephen,Naidoo, Jacinth,Rivera-Cancel, Giomar,Voruganti, Sukesh,Mallipeddi, Prema,Theodoropoulos, Panayotis C.,Geboers, Sophie,Chen, Hong,Ortiz, Francisco,Posner, Bruce,Nijhawan, Deepak,Ready, Joseph M.
, p. 9773 - 9786 (2020)
A series of N-acyl benzothiazoles shows selective and potent cytotoxicity against cancer cell lines expressing cytochrome P450 4F11. A prodrug form is metabolized by cancer cells into an active inhibitor of stearoyl-CoA desaturase (SCD). Substantial variation on the acyl portion of the inhibitors allowed the identification of (R)-27, which balanced potency, solubility, and lipophilicity to allow proof-of-concept studies in mice. The prodrugs were activated inside the tumor, where they can arrest tumor growth. Together, these observations offer promise that a tumor-activated prodrug strategy might exploit the essentiality of SCD for tumor growth, while avoiding toxicity associated with systemic SCD inhibition.
