- THERAPEUTICS TARGETING MUTANT ADENOMATOUS POLYPOSIS COLI (APC) FOR THE TREATMENT OF CANCER
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The present disclosure reports an extensive medicinal chemistry evaluation of a large collection of Truncating APC-Selective Inhibitor (TASIN) compounds. The compounds were evaluated for activity against a series of colon cancer cell lines with and withou
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Paragraph 00435; 00437; 00441; 00443-00444
(2020/07/04)
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- Design and Synthesis of TASIN Analogues Specifically Targeting Colorectal Cancer Cell Lines with Mutant Adenomatous Polyposis Coli (APC)
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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.
- Wang, Wentian,Zhang, Lu,Morlock, Lorraine,Williams, Noelle S.,Shay, Jerry W.,De Brabander, Jef K.
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p. 5217 - 5241
(2019/05/28)
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- NOVEL ANALGESIC THAT BINDS FILAMIN A
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A compound, composition and method are disclosed that can provide analgesia. A contemplated compound has a structure that corresponds to Formula I, wherein R1 and R2 are substituents, and n, W, X and Y are defined within.
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Page/Page column 34
(2010/12/29)
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