Neamati, Nouri - University of Michigan

个人简介

Nouri Neamati is the John G. Searle Professor of Medicinal Chemistry at the University of Michigan College of Pharmacy. He obtained a Ph.D. in biomedical sciences from the University of Texas Graduate School of Biomedical Sciences and M.D. Anderson Cancer Center, Houston, Texas in 1995. From 1995 to 2000 he was a postdoctoral fellow and a research fellow at the National Institutes of Health. In September 2000, he joined the University of Southern California School of Pharmacy with a joint appointment at the Norris Comprehensive Cancer Center, rising to the rank of professor in 2011.   Dr. Neamati is the recipient of numerous awards including the NIH Technology Transfer Award in 2000, STOP CANCER Award in 2001, GlaxoSmithKline Drug Discovery Award in 2002, BCRP and LCRP Concept Awards from the Department of Defense (DOD) in 2005 and 2009, LUNGevity Discovery Award, American Lung Association, 2006, The Littlefield-AACR Award in Metastatic Colon Cancer Research, in 2006, the Idea Awards in Ovarian and Breast Cancer from the DOD in 2006 and 2010, and a Concept Award in 2012. He has published 200 peer-reviewed manuscripts, 18 book chapters, and over 30 patents in the area of drug design and discovery. He has recently edited the first comprehensive and authoritative book on “HIV-1 Integrase: Mechanism and Inhibitor Design.” He has served in numerous study sections for NIH and DOD. He was the founding editor-in-chief of Current Molecular Pharmacology, an associate editor of Current Anticancer Drug Targets, and an editorial advisory board member of several journals including Expert Opinion on Drug Discovery, Expert Opinion on Investigational Drugs, Hormones & Cancer, and the Journal of Medicinal Chemistry.

研究领域

Areas of primary interest to my laboratory include 1) structure- and ligand-based drug design, 2) cellular and molecular pharmacology, and 3) preclinical drug development. Recently, we have discovered a series of promising small-molecule compounds and are performing in-depth preclinical pharmacology evaluation in anticipation for their translation into clinical studies. In recent years, we have built a robust chemoinformatic platform that has allowed us to design a series of highly promising small-molecule drugs for the treatment of various cancers and HIV-1 infection. At the heart of our chemoinformatic platform is a database of small-molecules consisting of 10 million compounds readily searchable in two dimensions. We have calculated up to 200 conformations for each compound to generate approximately 2 billion structures that are fully searchable in three dimensions. In an effort to expedite the success rate for drug development, we have also calculated a host of 200 ADMET descriptors for each compound and are routinely simulating their PK/PD properties prior to their actual testing in vitro. An in-house library of 40,000 highly diverse drug-like compounds with desirable ADMET properties is being evaluated in a host of in vitro assays. We have in place several cell and animal models of various human cancers useful for mechanistic and preclinical studies. Elucidating the mechanism of action of highly valuable candidate compounds is a major focus of our laboratory. As a result, we have several promising drugs that are currently at various stages of development. RESEARCH INTERESTS Structure- and ligand-based drug design Cellular and molecular pharmacology Preclinical drug development Select targets of interest include: ER stress (GRP78 and PDI); DNA-binding proteins (HIV-1 integrase, APE-1); Protein-protein interactions (HIV-1 integrase-LEDGF/p75, integrin  v  3 , BCL2, MDM2-p53); GPCRs (CXCR2, CXCR4); Mitochonrial-targeted agents; Transcription factors (STAT3, Nrf2)

近期论文

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Shergalis, A.; Bankhead, A., 3rd; Luesakul, U.; Muangsin, N.; Neamati, N. Current challenges and opportunities in treating glioblastoma. Pharmacol Rev 2018, 70, 412-445. Xu, S.; Liu, Y.; Yang, K.; Wang, H.; Shergalis, A.; Kyani, A.; Bankhead III, A.; Tamura, S.; Yang, S.; Wang, X.; Wang, C.-C.; Rehemtulla, A.; Ljungman, M.; Neamati, N., Inhibition of protein disulfide isomerase in glioblastoma causes marked downregulation of DNA repair and DNA damage response genes. Theranostics 2019, 9, 2282-2298. Liu, Y.; Ji, W.; Shergalis, A.; Xu, J.; Delaney, A. M.; Calcaterra, A.; Pal, A.; Ljungman, M.; Neamati, N.; Rehemtulla, A. Activation of the unfolded protein response via inhibition of protein disulfide isomerase decreases the capacity for DNA repair to sensitize glioblastoma to radiotherapy. Cancer Res 2019, 79, 2923-2932. Sanna, V.; Nurra, S.; Pala, N.; Marceddu, S.; Pathania, D.; Neamati, N.; Sechi, M. Targeted nanoparticles for the delivery of novel bioactive molecules to pancreatic cancer cells. J Med Chem 2016, 59, 5209-5220 Xu, S.; Adisetiyo, H.; Tamura, S.; Grande, F.; Garofalo, A.; Roy-Burman, P.; Neamati, N. Dual inhibition of survivin and MAOA synergistically impairs growth of PTEN-negative prostate cancer. Br J Cancer 2015, 113, 242-51 Kuang, Y.; El-Khoueiry, A.; Taverna, P.; Ljungman, M.; Neamati, N. Guadecitabine (SGI-110) priming sensitizes hepatocellular carcinoma cells to oxaliplatin. Mol Oncol 2015, 9, 1799-814 Pathania, D.; Kuang, Y.; Sechi, M.; Neamati, N. Mechanisms underlying the cytotoxicity of a novel quinazolinedione-based redox modulator, QD232, in pancreatic cancer cells. Br J Pharmacol 2015, 172, 50-63 Ha, H.; Bensman, T.; Ho, H.; Beringer, P. M.; Neamati, N. A novel phenylcyclohex-1-enecarbothioamide derivative inhibits CXCL8-mediated chemotaxis through selective regulation of CXCR2-mediated signalling. Br J Pharmacol 2014, 171 (6), 1551-65 Ha, H.; Neamati, N. Pyrimidine-based compounds modulate CXCR2-mediated signaling and receptor turnover. Mol Pharmaceutics 2014, 11(7), 2431-41 Pathania, D.; Sechi, M.; Palomba, M.; Sanna, V.; Berrettini, F.; Sias, A.; Taheri, L.; Neamati, N., Design and discovery of novel quinazolinedione-based redox modulators as therapies for pancreatic cancer. Biochim Biophys Acta 2014, 1840 (1), 332-43 Kim, K.; Kim, J. M.; Kim, J. S.; Choi, J.; Lee, Y. S.; Neamati, N.; Song, J. S.; Heo, K.; An, W. VprBP has intrinsic kinase activity targeting histone H2A and represses gene transcription. Molecular Cell 2013, 52, 459-67 Xu, S.; Sankar, S.; Neamati, N. Protein disulfide isomerase: a promising target for cancer therapy. Drug Discov Today 2014, 19 (3), 222-40 Millard, M.; Gallagher, J. D.; Olenyuk, B. Z.; Neamati, N. A selective mitochondrial-targeted chlorambucil with remarkable cytotoxicity in breast and pancreatic cancers. J Med Chem 2013, 56, 9170-79 Xu, S.; Grande, F.; Garofalo, A.; Neamati, N. Discovery of a novel orally active small-molecule gp130 inhibitor for the treatment of ovarian cancer. Mol Cancer Ther. 2013, 12, 937-949 Xu, S.; Butkevich, A. N.; Yamada, R.; Zhou, Y.; Debnath, B.; Duncan, R.; Zandi, E.; Petasis, N. A.; Neamati, N. Discovery of an orally active small-molecule irreversible inhibitor of protein disulfide isomerase for ovarian cancer treatment. Proc Natl Acad Sci U S A 2012, 109, 16348-16353.