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• W2944051149 abstract "Despite advances in targeted anticancer therapies, there are still no small-molecule-based therapies available that specifically target colorectal cancer (CRC) development and progression, the second leading cause of cancer deaths. We previously disclosed the discovery of truncating adenomatous polyposis coli (APC)-selective inhibitor 1 (TASIN-1), a small molecule that specifically targets colorectal cancer cells lines with truncating mutations in the adenomatous polyposis coli (APC) tumor suppressor gene through inhibition of cholesterol biosynthesis. Here, we report a medicinal chemistry evaluation of a collection of TASIN analogues and activity against colon cancer cell lines and an isogenic cell line pair reporting on the status of APC-dependent selectivity. A number of potent and selective analogues were identified, including compounds with good metabolic stability and pharmacokinetic properties. The compounds reported herein represent a first-in-class genotype-selective series that specifically target apc mutations present in the majority of CRC patients and serve as a translational platform toward a targeted therapy for colon cancer." @default.
• W2944051149 created "2019-05-16" @default.
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• W2944051149 date "2019-05-09" @default.
• W2944051149 modified "2023-10-16" @default.
• W2944051149 title "Design and Synthesis of TASIN Analogues Specifically Targeting Colorectal Cancer Cell Lines with Mutant Adenomatous Polyposis Coli (APC)" @default.
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• W2944051149 doi "https://doi.org/10.1021/acs.jmedchem.9b00532" @default.
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• W2944051149 hasPublicationYear "2019" @default.
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