Wang, Shaomeng - University of Michigan - Comprehensive Cancer Center

个人简介

Dr. Wang received his B.S. in Chemistry from Peking University in 1986 and his Ph.D. in Chemistry from Case Western Reserve University in 1992. Dr. Wang did his postdoctoral training in drug design at the National Cancer Institute, NIH between1992-1996. Dr. Wang was Assistant Professor at Georgetown University from 1996-2000 and Associate Professor from 2000-2001. Dr. Wang joined the faculty at the University of Michigan Medical School as a tenured Associate Professor in 2001 and was promoted to Professor in 2006. Dr. Wang was named the Warner-Lambert/Parke-Davis Professor in Medicine in 2007. Dr. Wang serves as the Co-Director of the Molecular Therapeutics Program at the University of Michigan Comprehensive Cancer Center and is the Director of the Cancer Drug Discovery Program at the University of Michigan. Dr. Wang is the Editor-in-Chief for Journal of Medicinal Chemistry, a premier international journal in medicinal chemistry and drug discovery by the American Chemical Society and serves on the editorial board for several international journals. Dr. Wang has published more than 200 papers in peer-reviewed scientific journals and 100+ meeting abstracts, and is an inventor on more than 40 patents and patent applications. In addition to his academic role, Dr Wang is a co-founder of Ascenta Therapeutics and Ascentage Pharma, which were established to develop innovative anticancer medicines with technologies licensed mainly from the University of Michigan.

研究领域

1. A small-molecule inhibitor (AT-101) which targets Bcl-2/Bcl-xL/Mcl-1 - Phase II clinical trials for the treatment of solid and non-solid human cancer. 2. An orally active small-molecule IAP antagonist (AT-406/Debio1143) - Phase II clinical trials (NCT02022098) for the treatment of solid and non-solid human cancer. 3. An MDM2 inhibitor (AA-115/APG-115) - Phase II clinical trials (NCT02935907) for the treatment of advanced solid tumors of lymphoma. 4. A small-molecule inhibitor (BM-1252/APG-1252) which targets Bcl-2/Bcl-xL/Mcl-1 - Phase I clinical trials (NCT03080311) for the treatment of SCLC and other solid tumors. 5. A small-molecule IAP antagonist (SM-1287/APG-1387) - Phase I clinical trials in China for the treatment of human cancers.

近期论文

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Zhou H, Lu J, Liu L, Bernard D, Yang CY, Fernandez-Salas E, Chinnaswamy K, Layton S, Stuckey J, Yu Q, Zhou W, Pan Z, Sun Y, Wang S. A potent small-molecule inhibitor of the DCN1-UBC12 interaction that selectively blocks cullin 3 neddylation. Nat Commun. 2017 Oct 27;8(1):1150. doi: 10.1038/s41467-017-01243-7. Karatas H, Li Y, Liu L, Ji J, Lee S, Chen Y, Yang J, Huang L, Bernard D, Xu J, Townsend EC, Cao F, Ran X, Li X, Wen B, Sun D, Stuckey JA, Lei M, Dou Y, Wang S. Discovery of a Highly Potent, Cell-Permeable Macrocyclic Peptidomimetic (MM-589) Targeting the WD Repeat Domain 5 Protein (WDR5)-Mixed Lineage Leukemia (MLL) Protein-Protein Interaction. J Med Chem. 2017 Jun 22;60(12):4818-4839. Zhao Y, Bai L, Liu L, McEachern D, Stuckey JA, Meagher JL, Yang CY, Ran X, Zhou B, Hu Y, Li X, Wen B, Zhao T, Li S, Sun D, Wang S. Structure-Based Discovery of 4-(6-Methoxy-2-methyl-4-(quinolin-4-yl)-9H-pyrimido[4,5-b]indol-7-yl)-3,5-dimethylisoxazole (CD161) as a Potent and Orally Bioavailable BET Bromodomain Inhibitor. J Med Chem. 2017 May 11;60(9):3887-3901. Wang X, Qiao Y, Asangani IA, Ateeq B, Poliakov A, Cieślik M, Pitchiaya S, Chakravarthi BVSK, Cao X, Jing X, Wang CX, Apel IJ, Wang R, Tien JC, Juckette KM, Yan W, Jiang H, Wang S, Varambally S, Chinnaiyan AM. Development of Peptidomimetic Inhibitors of the ERG Gene Fusion Product in Prostate Cancer. Cancer Cell. 2017 Apr 10;31(4):532-548.e7. Aguilar A, Lu J, Liu L, Du D, Bernard D, McEachern D, Przybranowski S, Li X, Luo R, Wen B, Sun D, Wang H, Wen J, Wang G, Zhai Y, Guo M, Yang D, Wang S. Discovery of 4-((3'R,4'S,5'R)-6″-Chloro-4'-(3-chloro-2-fluorophenyl)-1'-ethyl-2″-oxodispiro[cyclohexane-1,2'-pyrrolidine-3',3″-indoline]-5'-carboxamido)bicyclo[2.2.2]octane-1-carboxylic Acid (AA-115/APG-115): A Potent and Orally Active Murine Double Minute 2 (MDM2) Inhibitor in Clinical Development. J Med Chem. 2017 Apr 13;60(7):2819-2839. Zhou B, Hu J, Xu F, Chen Z, Bai L, Fernandez-Salas E, Lin M, Liu L, Yang CY, Zhao Y, McEachern D, Przybranowski S, Wen B, Sun D, Wang S. Discovery of a Small-Molecule Degrader of Bromodomain and Extra-Terminal (BET) Proteins with Picomolar Cellular Potencies and Capable of Achieving Tumor Regression. J Med Chem. 2017 Mar 24. doi: 10.1021/acs.jmedchem.6b01816. Wang X, Cao W, Zhang J, Yan M, Xu Q, Wu X, Wan L, Zhang Z, Zhang C, Qin X, Xiao M, Ye D, Liu Y, Han Z, Wang S, Mao L, Wei W, Chen W. A covalently bound inhibitor triggers EZH2 degradation through CHIP-mediated ubiquitination. EMBO J. 2017 May 2;36(9):1243-1260. Bai L, Zhou B, Yang CY, Ji J, McEachern D, Przybranowski S, Jiang H, Hu J, Xu F, Zhao Y, Liu L, Fernandez-Salas E, Xu J, Dou Y, Wen B, SunD, Meagher J, Stuckey J, Hayes DF, Li S, Ellis MJ, Wang S. Targeted Degradation of BET Proteins in Triple-Negative Breast Cancer. Cancer Res. 2017 May 1;77(9):2476-2487. Peterson LF, Lo MC, Liu Y, Giannola D, Mitrikeska E, Donato NJ, Johnson CN, Wang S, Mercer J, Talpaz M. Induction of p53 suppresses chronic myeloid leukemia. Leuk Lymphoma. 2017 Sep;58(9):1-14. N�r F, Warner KA, Zhang Z, Acasigua GA, Pearson AT, Kerk SA, Helman JI, Sant'Ana Filho M, Wang S, N�r JE. Therapeutic Inhibition of the MDM2-p53 Interaction Prevents Recurrence of Adenoid Cystic Carcinomas. Clin Cancer Res. 2017 Feb 15;23(4):1036-1048. Ashley SL, Sisson TH, Wheaton AK, Kim KK, Wilke CA, Ajayi IO, Subbotina N, Wang S, Duckett CS, Moore BB, Horowitz JC. Targeting Inhibitor of Apoptosis Proteins Protects from Bleomycin-Induced Lung Fibrosis. Am J Respir Cell Mol Biol. 2016 Apr;54(4):482-92. Liu L, Lei I, Karatas H, Li Y, Wang L, Gnatovskiy L, Dou Y, Wang S, Qian L, Wang Z. Targeting Mll1 H3K4 methyltransferase activity to guide Cardiac lineage specific reprogramming of fibroblasts. Cell Discov. 2016 Oct 11;2:16036. Ying ZX, Jin M, Peterson LF, Bernard D, Saiya-Cork K, Yildiz M, Wang S, Kaminski MS, Chang AE, Klionsky DJ, Malek SN. Recurrent Mutations in the MTOR Regulator RRAGC in Follicular Lymphoma. Clin Cancer Res. 2016 Nov 1;22(21):5383-5393. Fernandez-Salas E, Wang S, Chinnaiyan AM. Role of BET proteins in castration-resistant prostate cancer. Drug Discov Today Technol. 2016 Mar;19:29-38. Lu J, McEachern D, Li S, Ellis MJ, Wang S. Reactivation of p53 by MDM2 Inhibitor MI-77301 for the Treatment of Endocrine-Resistant Breast Cancer. Mol Cancer Ther. 2016 Dec;15(12):2887-2893. Xu J, Li L, Xiong J, denDekker A, Ye A, Karatas H, Liu L, Wang H, Qin ZS, Wang S, Dou Y. MLL1 and MLL1 fusion proteins have distinct functions in regulating leukemic transcription program. Cell Discov. 2016 May 17;2:16008. Swiecicki PL, Bellile E, Sacco AG, Pearson AT, Taylor JM, Jackson TL, Chepeha DB, Spector ME, Shuman A, Malloy K, Moyer J, McKean E, McLean S, Sukari A, Wolf GT, Eisbruch A, Prince M, Bradford C, Carey TE, Wang S, N�r JE, Worden FP. A phase II trial of the BCL-2 homolog domain 3 mimetic AT-101 in combination with docetaxel for recurrent, locally advanced, or metastatic head and neck cancer. Invest New Drugs. 2016 Aug;34(4):481-9. Feng FY, Zhang Y, Kothari V, Evans JR, Jackson WC, Chen W, Johnson SB, Luczak C, Wang S, Hamstra DA. MDM2 Inhibition Sensitizes Prostate Cancer Cells to Androgen Ablation and Radiotherapy in a p53-Dependent Manner. Neoplasia. 2016 Apr;18(4):213-22. Zhang H, Gayen S, Xiong J, Zhou B, Shanmugam AK, Sun Y, Karatas H, Liu L, Rao RC, Wang S, Nesvizhskii AI, Kalantry S, Dou Y. MLL1 Inhibition Reprograms Epiblast Stem Cells to Naive Pluripotency. Cell Stem Cell. 2016 Apr 7;18(4):481-94