DJ-Dior
DJ-Dior
Zhang Ao, male, doctor, researcher of Shanghai Institute of pharmacy, Chinese Academy of Sciences, doctoral supervisor, winner of national fund for Distinguished Young Scholars, winner of "100 Talents Program" of Chinese Academy of Sciences and excellent award of Shanghai "Pujiang talent program". Now he is the distinguished professor of School of life science and technology, Shanghai University of science and technology.
Mainly engaged in chemical biology and pharmaceutical chemistry research, especially for neuropsychiatric and cancer two major difficult diseases, targeting G-protein coupled receptor (GPCR) and receptor tyrosine kinase (RTK), which are of great significance and challenge in drug research, systematically developed efficient synthesis, structural optimization and construction of focused compound library based on drug like dominant skeleton More than 100 active compounds were obtained.
Character experience
Education experience 1988 / 09 – 1992 / 07, Department of chemistry, West China Normal University, Sichuan, Bachelor 1992 / 09 – 1995 / 06, Nankai University, Tianjin, Institute of elemental organic chemistry, master 1995 / 07 – 1997 / 08, Shanghai Institute of organic chemistry, Chinese Academy of Sciences, Research Intern 1997 / 09 – 2000 / 10, Shanghai Institute of organic chemistry, Chinese Academy of Sciences, doctor 2001 / 02 – 2002 / 03, medical school, Georgetown University, USA From April 2002 to February 2006, he worked in Harvard Medical School, McLean branch. He was the instructor of Harvard Medical School, the consultant mentor of graduate class of Harvard Medical School, and the assistant director of Pharmaceutical Chemistry Research Office of McLean branch from 2006 to 2006. He worked in Shanghai Institute of pharmacy, Chinese Academy of Sciences, and won the preferential support of "100 talents plan" of Chinese Academy of Sciences.
Research direction
1. Design, synthesis and optimization of molecular targeted drugs acting on tyrosine kinase or GPCR, focusing on drug-resistance. 2. Discovery of new structure and mechanism of small molecule drugs based on total synthesis of natural products and new synthetic methods. 3. Mainly engaged in chemical biology and pharmaceutical chemistry research, especially for neuropsychiatric and cancer two major difficult diseases, targeting G-protein coupled receptor (GPCR) and receptor tyrosine kinase (RTK), which are of great significance and challenge in drug research, systematically carried out efficient synthesis, structural optimization and construction of focused compound library based on drug like dominant skeleton Construction research.
Main contributions
More than 100 active compounds have been obtained. Among them, atpm-et, a kappa receptor agonist designed for the high addiction of existing central analgesics, has entered the preclinical research system as a new type of low addictive analgesics. Aiming at the disadvantage that selective dopamine receptor agonist anti Parkinson drugs are prone to dyskinesia, atpm-et is the first in the world to carry out dual drug therapy with D2 and 5-HT1A receptors Mcl-135, as a low toxicity and effective new anti Parkinson drug candidate, is undergoing early preclinical research. It is the first time to complete the synthesis of the basic skeleton of marmycina, a natural product, in the world, and construct a library of carbazole based dominant skeleton compounds by inserting the dominant pharmacophore of kinase inhibitor Targeting tyrosine kinase c-met specific inhibitors, we also obtained high activity inhibitors of PARP1, which have strong anti-tumor activity in vivo and in vitro. It has entered the preclinical systematic efficacy and safety evaluation, and has great development prospects. More than 90 SCI papers have been published, including 12 papers published in < I > Journal of pharmaceutical chemistry < / I > and 35 domestic and international patents applied by the first applicant. He has been invited to write reviews and prospects for chemrev, medresrev, jmedchem, etc. on new drug discovery strategies, new ideas and related drug R & D progress, and act as reviewer of many international journals. presided over and completed the major special projects of national major new drug creation and development in the 11th five year plan, National Natural Science Foundation and other projects; is presided over the major special projects of national major new drug creation and development in the 12th Five Year Plan, national outstanding youth projects and other important projects. in recent years, we have carried out in-depth and systematic research work around the basic and applied subjects of pharmaceutical chemistry. We have developed a series of efficient and rapid synthesis methods for the active compound skeleton, and optimized the structure of the discovered lead compounds by using the concept of pharmaceutical chemistry, and obtained many candidate compounds with good activity and high medicinal properties. Among them: < br > 1 Adv.Syn.Catal (I > 2014), palladium catalyzed intramolecular cyclization to synthesize cinnoline (< I > 2014) Chem.Commun (I > 2014) and palladium catalyzed oxidative addition of alkynyl to synthesize edaravone amino derivatives (< I > 2014) Org.Lett (I > 2014), indium catalyzed sugar ring rearrangement Response (< I > 0 Org.Lett The synthesis of tetrahydroisoquinoline (< I > 2013) by iron induced ring condensation of benzodiazepine Chem.Eur J. < / I > 2009), silver catalyzed free radical decarboxylation and alkylation to synthesize naphthoquinone (J Org.Chem (I > 2009), iridium catalyzed asymmetric hydrogenation of acrylic acid and polysubstituted acrylamide (< I > 2009) Chem.Commun One pot three-step synthesis of carbazole derivatives (< I > 2010) Adv.Syn.Catal .(2010) and other methods, which are original scientific research achievements and highly praised and cited by international peers;
2. In terms of new methods and new concepts of drug optimization design, based on the matching properties of drug-target interaction characteristics and drug drug drug-forming advantages, aiming at the two major difficult diseases of neuropsychiatric and tumor, we took the lead in carrying out molecular targeting with G-protein coupled receptor and tyrosine kinase in China Small molecule drug research, including: < br > (1) design and found that 5-HT 1A receptor agonists have good anti anxiety effect (< I > J Med.Chem (2) according to the multiple causes of Parkinson's disease, we designed and synthesized the candidate drugs targeting dopamine and serotonin dual agonists (< I > J Med.Chem (I > 2011); < br > (3) from the structure of natural products The specific tyrosine kinase c-met inhibitor was obtained and showed good antitumor activity in vitro and in vivo (< I > J Med.Chem (4) according to the synergetic lethal mechanism, we designed and found that PARP inhibitors targeting at Poly (adenosine diphosphate ribose) polymerase have obvious antitumor potential (< I > J Med.Chem (I > 2013); < br > (5) the relationship between gene mutation and drug resistance The aim of this study was to design and find a novel inhibitor of ALK, which has significant antitumor activity against wild-type and mutant ALK (< I > J Med.Chem .2014)。
All these works are international research hotspots in corresponding fields and play a leading role in China. 3. In the aspect of new drug discovery, a class of low addictive analgesics targeting к receptor has been developed in view of the high addiction of existing opioid receptor agonists, and the candidate compound atpm-et has entered the preclinical study of the system; and a novel compound with dual action mechanism of D2 and 5-HT1A receptor has been designed and synthesized in view of the disadvantage that classic antiparkinsonian drugs are prone to produce dyskinesia The candidate compound mcl-135, as a low toxicity and effective new anti Parkinson drug, is under early preclinical research; ③ as a class I anti-tumor drug candidate, somcl-9112, a targeted poly (ADP ribose polymerase) PARP inhibitor, is under systematic preclinical research, and is expected to complete the clinical trial application by the end of 2015. so far, he has published more than 90 SCI papers and cited more than 1000 times, including 12 papers published in the Journal of pharmaceutical chemistry. The first applicant applied for 35 domestic and international patents. Invited to write reviews for chemical reviews, medical research reviews, etc. He has presided over more than 10 projects of NSFC, Ministry of science and technology, Chinese Academy of Sciences and Shanghai Science and Technology Commission. He has rich research background in the field of pharmaceutical chemistry, and his research team has made outstanding achievements in the design and synthesis of molecular targeted drugs. The research work will greatly promote the development of pharmaceutical chemistry and new drug research in China, and promote the development of pharmaceutical industry in China. project undertaken
1. Major national science and technology project for new drug creation in the 12th Five Year Plan, research on the drug properties of tyrosine kinase c-met specific inhibitors, 2011-2014, host < br > 2. National Fund for Distinguished Young Scholars, basic research on medicinal chemistry in new drug discovery, 2
Chinese PinYin : Zhang Ao
DJ-Dior
