The Novel Small-Molecule SR18662 Efficiently Inhibits the Growth of Colorectal Cancer In Vitro and In Vivo.

ABSTRACT: Krüppel-like factor 5 (KLF5), a member of the SP/KLF family of zinc finger transcription factors, is overexpressed in human colorectal cancer specimens, and this overabundance is associated with aggressive cancer development and progression. We demonstrated that mice haploinsufficient for Klf5 had reduced intestinal tumor burden in the background of germline mutation in Apc, a gatekeeper of intestinal tumorigenesis. Based on a high-throughput screening strategy, we developed ML264, a small-molecule compound that inhibits KLF5, and showed that it inhibits growth of colorectal cancer in vitro and in vivo Through optimization efforts based on the structure of ML264, we have now identified a new lead compound, SR18662. We find that treatment with SR18662 significant

SUBMITTER: Kim J 

PROVIDER: S-EPMC6825545 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature