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A new class of proteasome inhibitors was synthesized using lithocholic acid as a scaffold. Modification at the C-3 position of lithocholic acid with a series of acid acyl groups yielded compounds with a range of potency on proteasome inhibition. Among them, the phenylene diacetic acid hemiester derivative (13) displayed the most potent proteasome inhibition with IC(50) = 1.9 μM. Enzyme kinetic analysis indicates that these lithocholic acid derivatives are noncompetitive inhibitors of the proteasome. Copyright © 2011 Elsevier Ltd. All rights reserved.


Zhao Dang, Andrew Lin, Phong Ho, Dominique Soroka, Kuo-Hsiung Lee, Li Huang, Chin-Ho Chen. Synthesis and proteasome inhibition of lithocholic acid derivatives. Bioorganic & medicinal chemistry letters. 2011 Apr 1;21(7):1926-8

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PMID: 21388808

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