Ya-Qiu Long is currently a Professor at College of Pharmaceutical Sciences, Soochow University. She gained her BA (Hons) in Chemistry (1990) from Sichuan University and obtained her MS in Organic Chemistry (1993) at Shanghai Institute of Organic Chemistry, CAS, where she also achieved her Ph.D. (1996) for the work on the hydrophobic interaction-driven self-assembly study of phospholipids. After 3 years' postdoctoral training in the field of medicinal chemistry and bioorganic chemistry at National Institutes of Health, USA (1997-2000), she joined the faculty at Shanghai Institute of Materia Medica as a Hundred Talent Award recipient from CAS, appointed to a full professor and principal investigator (2001-2017). From March of 2017, she moved to Soochow University as a distinguished professor and vice dean of the medical college. Since 2001, she has supervised 24 PhD students, 13 master students and 2 postdoctoral coworkers. This has been possible by attracting a research portfolio of 27 grants, resulting in the publication of more than 90 peer reviewed papers (including JACS, JMC, OL, JOC), and invitations to deliver ca. 27 international and national presentations. Notably, she has obtained several highly prestigious awards and fellowships. For example, she is awarded the esteemed National Science Fund for Distinguished Young Scholars from NSFC and a Chinese Youth Science and Technology Award form the central government.
Long group is focused on the design, synthesis and SAR study of bioactive small molecules and peptidomimetics that may lead to the development of chemotherapeutic agents for cancer, AIDS and diabetes, by targeting the crucial enzyme or receptor involved in the etiological pathways. Meanwhile, our SAR studies reveal the structural information of the target protein which in turn facilitates the rational design and structural optimization of the lead compounds. Furthermore, we are interested in developing novel metal-free C-H functionalization methodologies to construct privileged scaffolds efficiently and conveniently, then study the bioactivity diversity resulting from the chemical structure diversity. Consequently, our study has provided new structural scaffolds and pharmacophore models for further development of HIV-1 integrase inhibitors, CCR5/CXCR4 antagonists and pTyr-dependent cell signaling inhibitors, resulting in 31 patents applications, among which 17 patents were licensed. Several lead compounds have entered preclinical evaluation stage with promising drug-likeness.
EDUCATION
09/01/1986 – 06/30/1990 Department of Chemistry, Sichuan University, Chengdu 610064, China, B.S.
09/01/1990 – 06/30/1993 Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China, M.S.
07/01/1993 – 10/30/1993 Department of Chemical Science and Technology, Faculty of Engineering, Kyushu University, Japan, Exchange Student
09/01/1993 – 06/30/1996 Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China, Ph.D.
WORK EXPERIENCE
07/01/1996 – 07/30/1997,Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200031, China, Assistant Professor, Project Leader
08/10/1997 – 09/30/2000,National Cancer Institute, National Institutes of Health, Bethesda, MD, USA, Visiting Fellow
10/01/2000 – 12/31/2000,Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200031, China, Professor, Principal Investigator
01/01/2001 – 02/28/2017 Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China, Professor, Principal Investigator
03/01/201 - up to date,Medical College of Soochow University, Distinguished Professor, Principal Investigator
AWARDS
03/2011 Government Special Allowance, presented by the State Council of China;
12/2009 New Century National Hundred, Thousand and Ten Thousand Talent Award, presented by the Ministry of Human Resources and Social Security of China, the Ministry of Science and Technology, the Ministry of Education, the Ministry of Finance, National Development and Reform Commission, the National Science Foundation of China, and China Association for Science and Technology;
12/2007 Chinese Youth Science and Technology Award, presented by the Ministry of Central Organization of Chinese Community Party, the Ministry of Personnel of China, China Association for Science and Technology;
07/2006 Zhonghe Award for young peptide scientist, presented by Chinese Peptide Symposium-2006 Organizing Committee;
09/2004 Chinese Outstanding Young Female Scientist Award, presented by China Association for Science and Technology, All-China Women's Federation and Chinese National Commission for UNESCO;
06/2002 Rising Star Award, presented by Shanghai Municipal Committee of Science and Technology, China;
11/2000 Hundred Talent Award, presented by Chinese Academy of Sciences, China.
PROFESSIONAL ACTIVITIES
Editorial Board Member:
Frontiers in Chemistry (Chemical Biology Section) 2015 - present;
Current Cancer Drug Targets 2005 - present;
Current Molecular Pharmacology 2008 - present;
The Open Enzyme Inhibition Journal 2008 - present;
The Open Natural Product Journal 2008 - present;
Pharmaceutical Care and Research 2006 - present.
Professional Committees:
05/2008 - 2016:Member of the 4th and 5th council of Shanghai Municipal Scientific Rising Star Association;
01/2014 – up to date:Member of Female Chemists Committee of Chinese Chemical Society.
REPRESENTATIVE PUBLICATIONS (2010 - current)
1. Li, H.; Huang, Q.; Chen, C.; Xu, B.; Wang, H.-Y.*; Long, Y.-Q.* Discovery of Potent and Orally Bioavailable GPR40 Full Agonists Bearing Thiophen-2-ylpropanoic Acid Scaffold. J. Med. Chem. 2017, 60, 2697-2717.
2.Zhang, F.-H.; Debnath, B.; Xu, Z.-L.; Yang, L.-M.; Song, L.-R.; Zheng, Y.-T.; Neamati, N.* and Long, Y.-Q.* Discovery of novel 3-hydroxypicolinamides as selective inhibitors of HIV-1 integrase-LEDGF/p75 interaction. Eur. J. Med. Chem. 2017, 125, 1051-1063.
3.Liu, G.; Xue, D.; Yang, J.; Wang, J.; Liu, X.; Huang, W.; Li, J.; Long, Y.-Q.*; Tan, W.;* and Zhang, A.* Design, synthesis, and pharmacological Evaluation of 2?(2,5-Dimethyl-5,6,7,8-tetrahydroquinolin-8-yl)?N?aryl Propanamides as Novel Smoothened (Smo) Antagonists. J. Med. Chem. 2016, 59, 11050-11068.
4.Chen, C.; Li, H.; Long, Y.-Q.* GPR40 agonists for the treatment of type 2 diabetes mellitus: the biological characteristics and the chemical space. Bioorg. Med. Chem. Lett. 2016, 26(23), 5603-5612.
5.Cheng, Y.; Shen, J.; Peng, R.-Z.; Wang, G.-F.; Zuo, J.-P.*; Long, Y.-Q.* Structure-based optimization and derivatization of 2-substituted quinolone-based non-nucleoside HCV NS5B inhibitors with submicromolar cellular replicon potency. Bioorg. Med. Chem. Lett. 2016, 26, 2900-2906.
6.Gai, W.; Li, H.; Jiang, H.; Long, Y.*; Liu, D.* Crystal structures of SIRT3 reveal that the α2-α3 loop and α3-helix affect the interaction with long-chain acyl lysine. FEBS Letters 2016, 590, 3019-3028.
7.Hu, W.; Lin, J.-P.; Zhang, F.-H.; Song, L.-R.; Long, Y.-Q.* Direct Synthesis of 2-Aryl-4-quinolones via Transition Metal-free Intramolecular Oxidative C(sp3)-H/C(sp3)-H Coupling. Org. Lett. 2015, 17 (5), 1268–1271.
8.An, X.-D.; Liu, H.; Xu, Z.-L.; Jin, Y.; Peng, X.; Yao, Y.-M.*; Geng, M.*; Long, Y.-Q.* Discovery of Potent 1H-imidazo[4,5-b]pyridine-based c-Met Kinase Inhibitors via Mechanism-directed Structural Optimization. Bioorg. Med. Chem. Lett. 2015, 25, 708-716.
9.Qin, L.-H.; Li, X.G.; Wang, Z.L.; Yao, W.B.; Wang, H.; Xie, X.; Long, Y.-Q.* Pharmacophore Model-based Design and Synthesis of New Structure Small Molecule CCR2 Inhibitors. Acta Chimica Sinica 2015, 73 (7), 679-684.
10.Yang, C.; Zhang, Y.; Wang, J.; Li, L.; Wang, L.; Hu, M.; Xu, M.; Long, Y.-Q.; Rong. R.; Zhu, T. A Novel Cyclic Helix B Peptide Inhibits Dendritic Cell Maturation during Amelioration of Acute Kidney Graft Rejection. Cell Death & Disease 2015, 6, e1993, doi:10.1038/cddis.2015.338.
11.Yang, C.; Liu, J.; Li, L.; Hu, M.; Long, Y.-Q.; Liu, X.; Zhu, T.; Huang, X.,; Zhao, S.; Liu, S.; Rong, R. Proteome Analysis of Renoprotection Mediated by a Novel Cyclic Helix B Peptide in Acute Kidney Injury. Sci. Rep. 2015, 5, 18045. DOI: 10.1038/srep18045
12.Yang, C.; Cao, Y.; Zhang, Y.; Li, L.; Xu, M.; Long, Y.-Q.; Rong. R.; Zhu, T. Cyclic helix B peptide inhibits ischemia reperfusion?induced renal fibrosis via the PI3K/Akt/FoxO3a pathway. J. Transl. Med. 2015, 13, 355.
13.Yang, C.; Xu, Z.; Zhao, Z.; Li, L.; Zhao, T.; Peng, D.; Xu, M.; Rong, R.*; Long, Y.*; Zhu, T.* A Novel Proteolysis-resistant Cyclic Helix B Peptide Ameliorates Kidney Ischemia Reperfusion Injury. Biochim. Biophys. Acta-Mol. Basis Dis. 2014, 1842 (11), 2306–2317.. (IF: 5.089)
14.Lin, J.-P.; Zhang, F.-H.; Long, Y.-Q.* Solvent/oxidant-switchable synthesis of multisubstituted quinazolines and benzimidazoles via metal-free selective oxidative annulation of arylamidines. Org. Lett. 2014, 16, 2822-2825. (IF: 6.324)
15.Xue, D.; Long, Y.-Q.* Metal-Free TEMPO-Promoted C(sp3)–H Amination to Afford Multisubstituted Benzimidazoles. J. Org. Chem. 2014, 79, 4727-4734. (IF: 4.638)
16.Li, B.-W.; Zhang, F.-H.; Serrao, E.; Chen, H.; Sanchezc, T. W.; Yang, L.-M.; Neamati, N.; Zheng, Y.-T.; Wang, H.*; Long, Y.-Q.* Design and discovery of flavonoid-based HIV-1 integrase inhibitors targeting both the active site and the interaction with LEDGF/p75. Bioorg. Med. Chem. 2014, 22, 3146-3158. (IF: 2.951)
17.Zhi, Y.; Gao, L.-X.; Jin, Y.; Tang, C.-L.; Li, J.-Y.; Li, J.*; Long, Y.-Q.* 3-Carboxyl-4-quinolones as cell-permeable inhibitors of protein tyrosine phosphatase 1B. Bioorg. Med. Chem. 2014, 22, 3670-3683.
18.Wang, S.-F.; Lin, J.-P.; He, P.-L.; Zuo, J.-P.*; Long, Y.-Q.* 2-Aryl-3-carbonylquinolones: design, synthesis and biological evaulation of novel HCV NS5B polymerase inhibitors. Acta Chimica Sinica 2014, 72, 906-913 (Cover Paper). (IF: 0.874)
19.Serrao, E.; Xu, Z.-L.; Debnath, B.; Christ, F.; Debyser, Z.; Long, Y.-Q.* and Neamati, N.* Discovery of a novel 5-carbonyl-1H-imidazole-4-carboxamide class of inhibitors of the HIV-1 integrase-LEDGF/p75 interaction. Bioorg. Med. Chem. 2013, 21, 5963-5972.
20.Long, Y.-Q.*; Huang, S.-X.; Zawahir, Z.; Xu, Z.-L.; Li, H.-Y.; Sanchez, T.; Zhi, Y.; De Houwer, S.; Christ, F.; Debyser, Z.; Neamati, N.* Design of Cell-Permeable Stapled-Peptides as HIV-1 Integrase Inhibitors. J. Med. Chem. 2013, 56, 5601-5612. (IF: 5.480)
21.Lin, J.-P.; Long, Y.-Q.* Transition Metal-Free One-Pot Synthesis of 2-Substituted 3-Carboxy-4-Quinolone and Chromone Derivatives. Chem. Commun., 2013, 49 (46), 5313 - 5315. (IF: 6.718)
22.Xiaoxiao Sun, X. X.; Ai, M. D.; Wang, Y.; Shen, S. S.; Gu, Y.; Jin, Y.; Zhou, Z. Y.; Long, Y.-Q. and Yu, Q. Selective induction of tumor cell apoptosis by a novel P450-mediated reactive oxygen species (ROS) inducer methyl 3-(4-nitrophenyl) propiolate. J. Biol. Chem. 2013, 288, 8826-8837. (IF: 4.60)
23.Wang, Y.; Xu, Z.-L.; Ai, J.; Peng, X.; Lin, J.-P.; Ji, Y.-C.; Geng, M.-Y.*; Long, Y.-Q.* Investigation on the 1,6-naphthyridine motif: discovery and SAR study of 1H-imidazo[4,5-h][1,6]naphthyridin-2(3H)-one-based c-Met kinase inhibitors. Org. Biomol. Chem. 2013, 11 (9), 1545-1562. (IF: 3.487)
24.Peng, D. Xu, Z. L.; Yang, C. Rong, R.M.; Zhu, T.Y.*; Long, Y.Q.* Metabolically stabilized structural modification on the helix B surface peptide of erythropoietin: Design, synthesis and improved renoprotective effect. Scientia Sinica Chimica 2013, 43(8), 1033-1040. (in Chinese) (Cover paper)
25.Zeng, L.-F.; Wang, Y.; Kazemi, R.; Xu, S.; Xu, Z.-L.; Sanchez, T. W.; Yang, L.-M.; Debnath, B.; Odde, S.; Xie, H.; Zheng, Y.-T.; Ding, J.; Neamati, N. and Long, Y.-Q.* Repositioning HIV-1 integrase inhibitors for cancer therapeutics: 1,6-naphthyridine-7-carboxamide as a promising scaffold with drug-like properties. J. Med. Chem. 2012, 55(22), 9492-9509.
26.Cao, B.; Wang, Y.; Ding, K.; Neamati, N.; Long, Y.-Q.* Synthesis of the pyridinyl analogues of dibenzylideneacetone (pyr-dba) via an improved Claisen-Schmidt condensation, displaying diverse biological activities as curcumin analogues. Org. Biomol. Chem. 2012, 10, 1239-1245.
27.Liu, Z.-L.; Zhou, Z.-Y.; Tian, W.; Fan, X.; Xue, D.; Yu, Q.*; Long, Y.-Q.* Discovery of novel 2-N-aryl substituted benzenesulfonamidoacetamides: orally bioavailable tubulin polymerization inhibitors with marked antitumor activities. ChemMedChem 2012, 7(4), 680-693. (IF: 3.046)
28.Huang, S.-X.; Cao, B.; Morisseau, C.; Jin, Y.; Hammock, B. D.; Long, Y.-Q.* Structure-based optimization of the piperazino-containing 1,3-disubstituted ureas affording sub-nanomolar inhibitors of soluble epoxide hydrolase. Med. Chem. Commun. 2012, 3, 379-384. (IF: 2.626)
29.Huang, S.-X.; Wang, Y.; Long, Y.-Q.* Advances in the research of human soluble epoxide hydrolase inhibitors. Chinese J. Org. Chem. 2012, 32(5), 877-888 (in Chinese). (IF: 0.858)
30.Fan, X.; Zhang, F.-H.; Al-Safi, R. I.; Zeng, L.-F.; Shabaik, Y.; Debnath, B.; Sanchez, T. W.; Odde, S.; Neamati, N. and Long, Y.-Q.* Design of HIV-1 Integrase inhibitors targeting the catalytic domain as well as its interaction with LEDGF/p75: a scaffold hopping approach using salicylate and catechol groups. Bioorg. Med. Chem. 2011, 19(16), 4935-4952.
31.Peng, D.; Zhi, Y.; Xue, T.; Gao, H.-Y.; Long, Y.-Q.* The ligand-based structural optimization of Grb2-SH2 inhibitors: high affinity, low charge and reduced peptidic nature. Chinese J. Org. Chem. 2011, 31(12), 2019-2033 (in Chinese).
32.Wang, Y.; Long, Y.-Q.* Advances in Small-molecule Inhibitors of Protein Tyrosine Kinases. Chinese J. Org. Chem. 2011, 31(10), 1595-1606 (in Chinese).
33.Huang, S.-X.; Li, H.-Y.; Liu, J.-Y.; Morisseau, C.; Hammock, B. D. Long, Y.-Q.* Incorporation of piperazino functionality into 1,3-disubstituted urea as the tertiary pharmacophore affording potent inhibitors of soluble epoxide hydrolase with improved pharmacokinetic properties. J. Med. Chem. 2010, 53(23), 8376-8386.
34.Zhang, H.-S.; Feng, D.-Z.; Chen, L. and Long, Y.-Q.* Discovery of novel (S)-α-phenyl-γ-amino butanamide containing CCR5 antagonists via functionality inversion approach. Bioorg. Med. Chem. Lett. 2010, 20, 2219-2223. (IF: 2.331)
35.Fan, X.; Zhang, H.-S.; Chen, L. and Long, Y.-Q.* Efficient Synthesis and Identification of Novel Propane-1,3-diamino Bridged CCR5 Antagonists with Variation on the Basic Center Carrier. Eur. J. Med. Chem. 2010, 45(7), 2827-2840. (IF: 3.432)
36.Liu, J.-H.; Jin, Y.; Long, Y.-Q.* Synthesis of the C5-C30 fragment of cyclodidemniserinol trisulfate via I2-mediated deprotection and ring closure tandem reaction. Tetrahedron 2010, 66, 1267-1273. (IF: 2.817)
37.Tian, W.; Qin, L.; Song, Q.; He, L.; Ai, M.; Jin, Y.; Zhou, Z.; You, S.; Long, Y.-Q.; Yu, Q. A novel synthetic analog of 5, 8-disubstituted quinazolines blocks mitosis and induces apoptosis of tumor cells by inhibiting microtubule polymerization. PLoS ONE 2010, 5, e10499. (IF: 3.534)
