Design, Synthesis and Biological Evaluation of Noncovalent Inhibitors of Human CD38 NADase

ChemMedChemVolume 7, Issue 2 p. 223-228 Communication Design, Synthesis and Biological Evaluation of Noncovalent Inhibitors of Human CD38 NADase Dr. Yi Zhou, Dr. Yi Zhou State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191 (China)Search for more papers by this authorKai Yiu Ting, Kai Yiu Ting Department of Physiology, University of Hong Kong, Faculty of Medicine Building, 21 Sassoon Road, Hong Kong (China)Search for more papers by this authorConnie Mo Ching Lam, Connie Mo Ching Lam Department of Physiology, University of Hong Kong, Faculty of Medicine Building, 21 Sassoon Road, Hong Kong (China)Search for more papers by this authorAnna Ka Yee Kwong, Anna Ka Yee Kwong Department of Physiology, University of Hong Kong, Faculty of Medicine Building, 21 Sassoon Road, Hong Kong (China)Search for more papers by this authorJie Xia, Jie Xia State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191 (China)Search for more papers by this authorDr. Hongwei Jin, Dr. Hongwei Jin State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191 (China)Search for more papers by this authorDr. Zhenming Liu, Dr. Zhenming Liu State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191 (China)Search for more papers by this authorProf. Liangren Zhang, Corresponding Author Prof. Liangren Zhang liangren@bjmu.edu.cn State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191 (China)State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191 (China)Search for more papers by this authorProf. Hon Cheung Lee, Prof. Hon Cheung Lee Department of Physiology, University of Hong Kong, Faculty of Medicine Building, 21 Sassoon Road, Hong Kong (China)Search for more papers by this authorProf. Lihe Zhang, Prof. Lihe Zhang State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191 (China)Search for more papers by this author Dr. Yi Zhou, Dr. Yi Zhou State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191 (China)Search for more papers by this authorKai Yiu Ting, Kai Yiu Ting Department of Physiology, University of Hong Kong, Faculty of Medicine Building, 21 Sassoon Road, Hong Kong (China)Search for more papers by this authorConnie Mo Ching Lam, Connie Mo Ching Lam Department of Physiology, University of Hong Kong, Faculty of Medicine Building, 21 Sassoon Road, Hong Kong (China)Search for more papers by this authorAnna Ka Yee Kwong, Anna Ka Yee Kwong Department of Physiology, University of Hong Kong, Faculty of Medicine Building, 21 Sassoon Road, Hong Kong (China)Search for more papers by this authorJie Xia, Jie Xia State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191 (China)Search for more papers by this authorDr. Hongwei Jin, Dr. Hongwei Jin State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191 (China)Search for more papers by this authorDr. Zhenming Liu, Dr. Zhenming Liu State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191 (China)Search for more papers by this authorProf. Liangren Zhang, Corresponding Author Prof. Liangren Zhang liangren@bjmu.edu.cn State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191 (China)State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191 (China)Search for more papers by this authorProf. Hon Cheung Lee, Prof. Hon Cheung Lee Department of Physiology, University of Hong Kong, Faculty of Medicine Building, 21 Sassoon Road, Hong Kong (China)Search for more papers by this authorProf. Lihe Zhang, Prof. Lihe Zhang State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191 (China)Search for more papers by this author First published: 03 January 2012 https://doi.org/10.1002/cmdc.201100487Citations: 19Read the full textAboutPDF 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Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract Shoot the messenger! CD38 is a multifunctional enzyme responsible for the generation of calcium ion messengers. A structural optimization was carried out to develop noncovalent CD38 inhibitors based on hit compound S125 (top) (IC50=86 μM). The best compound inhibited CD38 NADase with an IC50 value of 4.7 μM (bottom). Molecular modeling was used to predict potentially important interactions between the inhibitor and enzyme. Citing Literature Supporting Information Detailed facts of importance to specialist readers are published as "Supporting Information". Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Filename Description cmdc_201100487_sm_miscellaneous_information.pdf675.9 KB miscellaneous_information Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. Volume7, Issue2February 6, 2012Pages 223-228 RelatedInformation