李國菠，男，博士，四川大學華西藥學院副教授，碩士生導師。
基本介紹
- 中文名：李國菠
- 國籍：中國
- 畢業院校：四川大學
- 學位/學歷：博士
- 職務：四川大學碩士生導師
- 職稱：副教授
人物經歷,研究興趣,研究方向,科研項目,學術任職,獲獎記錄,發表論文,
人物經歷
2005年9月~2009年6月 西華大學生物工程學院，製藥工程專業，本科
2009年9月~2011年9月 四川大學華西藥學院，藥物化學專業，碩士研究生（導師：楊勝勇教授）
2011年9月~2014年6月 四川大學生物治療國家重點實驗室藥物化學專業，博士研究生（導師：楊勝勇教授）
2014年7月~2015年7月 四川大學生物治療國家重點實驗室，博士後（導師：楊勝勇教授、陳宇綜教授）
2015年7月~2016年8月 英國牛津大學化學研究實驗室，博士後（導師：Christopher J. Schofield教授、院士）
2016年9月~至今 四川大學華西藥學院藥物化學系，特聘副研究員、副教授
2009年9月~2011年9月 四川大學華西藥學院，藥物化學專業，碩士研究生（導師：楊勝勇教授）
2011年9月~2014年6月 四川大學生物治療國家重點實驗室藥物化學專業，博士研究生（導師：楊勝勇教授）
2014年7月~2015年7月 四川大學生物治療國家重點實驗室，博士後（導師：楊勝勇教授、陳宇綜教授）
2015年7月~2016年8月 英國牛津大學化學研究實驗室，博士後（導師：Christopher J. Schofield教授、院士）
2016年9月~至今 四川大學華西藥學院藥物化學系，特聘副研究員、副教授
研究興趣
主要從事藥物設計學、藥物化學、化學生物學等交叉學科研究工作。以創新藥物研發為導向，針對臨床上重要的藥物靶標，發展靶標特異性藥物分子設計、靶標識別、藥物篩選等新方法與技術，以發現新型先導化合物，進而開展結構最佳化、小分子探針等研究，並結合結構生物學、生物物理、分子生物學等技術手段闡明作用機制，以期最終獲得具有臨床套用前景的小分子候選化合物
研究方向
- 藥物分子設計、靶標識別等方法研究
- 靶向金屬蛋白酶的藥物發現、小分子探針設計及作用機制研究
科研項目
國家自然科學基金面上項目，2019-2022，負責人，在研
2.國家自然基金青年科學基金，2016-2018，負責人，在研
3.四川省國際合作項目，2018-2020，負責人，在研
4.四川大學中青年科技人才培育項目，2019-2022，負責人，在研
5.四川大學引進人才科研啟動經費資助項目， 2017-2019，負責人，在研
6.國家博士後科學基金一等面上項目，2015-2016，負責人，結題
2.國家自然基金青年科學基金，2016-2018，負責人，在研
3.四川省國際合作項目，2018-2020，負責人，在研
4.四川大學中青年科技人才培育項目，2019-2022，負責人，在研
5.四川大學引進人才科研啟動經費資助項目， 2017-2019，負責人，在研
6.國家博士後科學基金一等面上項目，2015-2016，負責人，結題
學術任職
2019年7月起擔任Chinese Chemical Letters雜誌青年編委
2019年3月起擔任藥學學報、Acta Pharmaceutica Sinica B雜誌青年編委
2019年3月起擔任藥學學報、Acta Pharmaceutica Sinica B雜誌青年編委
獲獎記錄
2018年獲世界華人藥化會議優秀報告獎
2017年獲中國藥物化學學術會議優秀報告獎
2016年獲教育部高等學校自然科學一等獎(排名第4)
2015年獲四川省科技進步獎一等獎(排名第5)
2017年獲中國藥物化學學術會議優秀報告獎
2016年獲教育部高等學校自然科學一等獎(排名第4)
2015年獲四川省科技進步獎一等獎(排名第5)
發表論文
1.Wang, Y.-L.; Liu, S.; Yu, Z.-J.; Lei, Y.; Huang, M.-Y.; Yan, Y.-H.; Ma, Q.; Zheng, Y.; Deng, H.; Sun, Y.; Wu, C.; Yu, Y.; Chen, Q.; Wang, Z.; Wu, Y.*; Li, G.-B.* Structure-Based Development of (1-(3'-Mercaptopropanamido)methyl)boronic Acid Derived Broad-Spectrum, Dual-Action Inhibitors of Metallo- and Serine-β-Lactamases. J. Med. Chem. 2019.
2.Yang, L.-L.; Xu, W.; Yan, J.; Su, H.-L.; Yuan, C.; Li, C.; Zhang, X.; Yu, Z.-J.; Yan, Y.-H.; Yu, Y.; Chen, Q.; Wang, Z.; Li, L.; Qian, S.*; Li, G.-B.* Crystallographic and SAR analyses reveal the high requirements needed to selectively and potently inhibit SIRT2 deacetylase and decanoylase. MedChemComm 2019, 10, 164-168.
3.Yang, L.-L.; Wang, H.-L.; Zhong, L.; Yuan, C.; Liu, S.-Y.; Yu, Z.-J.; Liu, S.; Yan, Y.-H.; Wu, C.; Wang, Y.; Wang, Z.; Yu, Y.; Chen, Q.*; Li, G.-B.*, X-ray crystal structure guided discovery of new selective, substrate-mimicking sirtuin 2 inhibitors that exhibit activities against non-small cell lung cancer cells. Eur. J. Med. Chem. 2018, 155, 806-823.
4.Liu, S.; Jing, L.; Yu, Z.-J.; Wu, C.; Zheng, Y.; Zhang, E.; Chen, Q.; Yu, Y.; Guo, L.; Wu, Y.*; Li, G.-B.*, ((S)-3-Mercapto-2-methylpropanamido)acetic acid derivatives as metallo-β-lactamase inhibitors: Synthesis, kinetic and crystallographic studies. Eur. J. Med. Chem. 2018, 145, 649-660.
5.Zhang, C.; Pu, Y.-c.; Yu, Z.-J.; Wu, C.-y.; Brem, J.; McDonough, M. A.; Schofield, C. J.; Li, G.-B.*; Wu, Y.*, Rh(iii)-Catalyzed directed C-H carbenoid coupling reveals aromatic bisphosphonates inhibiting metallo- and Serine-β-lactamases. Organic Chemistry Frontiers 2018, 5, 1288-1292.
6.Yu, Z.-J.; Zhang, C.; Li, J.-L.; Liu, Y.-Z.; Yu, X.-L.; Guo, L.; Li, G.-B.*; Wu, Y.*, Rh(III)-Catalyzed, 1,2,3-Triazole-Assisted Directed C-H Coupling with Diazo Diphosphonates. Tetrahedron Letters 2018, 59, 2816-2819.
7.Yu, Z.-J.; Liu, S.; Zhou, S.; Li, H.; Yang, F.; Yang, L.-L.; Wu, Y.; Guo, L.; Li, G.-B.*, Virtual target screening reveals rosmarinic acid and salvianolic acid A inhibiting metallo- and serine-β-lactamases. Bioorg. Med. Chem. Lett. 2018, 28, 1037-1042.
8.Yang, Z.; Zhang, Y.; Chen, X.; Li, W.; Li, G.-B.*; Wu, Y.*, Total Synthesis and Evaluation of B-Homo Palmatine and Berberine Derivatives as p300 Histone Acetyltransferase Inhibitors. European Journal of Organic Chemistry 2018, 2018, 1041-1052.
9.Zhou, S.#; Li, G.-B.#; Luo, L.; Zhong, L.; Chen, K.; Li, H.; Jiang, X.-J.; Fu, Q.; Long, X.; Bao, J.-k., Structure-based discovery of new maternal embryonic leucine zipper kinase inhibitors. Organic & Biomolecular Chemistry 2018, 16, 1489-1495. (co-first author)
10.Liu, S.; Ji, S.; Yu, Z.-J.; Wang, H.-L.; Cheng, X.; Li, W.-J.; Jing, L.; Yu, Y.; Chen, Q.; Yang, L.-L.; Li, G.-B.*; Wu, Y.*, Structure-based discovery of new selective small-molecule sirtuin 5 inhibitors. Chemical Biology & Drug Design 2018, 91, 257-268.
11.Yang, L.; Ma, X.; He, Y.; Yuan, C.; Chen, Q.; Li, G.B.*; Chen, X.*, Sirtuin 5: a review of structure, known inhibitors and clues for developing new inhibitors. Sci. China Life Sci. 2017, 60, 249-256.
12.Wang, H.-L.; Liu, S.; Yu, Z.-J.; Wu, C.; Cheng, L.; Wang, Y.; Chen, K.; Zhou, S.; Chen, Q.; Yu, Y.*; Li, G.-B.*, Interactions between sirtuins and fluorogenic small-molecule substrates offer insights into inhibitor design. RSC Adv. 2017, 7, 36214-36222.
13.Li, G.-B.*; Yu, Z.-J.; Liu, S.; Huang, L.-Y.; Yang, L.-L.; Lohans, C. T.; Yang, S.-Y., IFPTarget: A Customized Virtual Target Identification Method Based on Protein–Ligand Interaction Fingerprinting Analyses. J. Chem. Inf. Model. 2017, 57, 1640-1651.
14.Li, G.-B.; Brem, J.; Lesniak, R.; Abboud, M. I.; Lohans, C. T.; Clifton, I. J.; Yang, S.-Y.; Jimenez-Castellanos, J.-C.; Avison, M. B.; Spencer, J.; McDonough, M. A.; Schofield, C. J., Crystallographic analyses of isoquinoline complexes reveal a new mode of metallo-β-lactamase inhibition. Chem. Commun. 2017, 53, 5806-5809.
15.Li, G.-B.; Abboud, M. I.; Brem, J.; Someya, H.; Lohans, C. T.; Yang, S.-Y.; Spencer, J.; Wareham, D. W.; McDonough, M. A.; Schofield, C. J., NMR-filtered virtual screening leads to non-metal chelating metallo-β-lactamase inhibitors. Chem. Sci. 2017, 8, 928-937.
16.Li, G.-B.; Ma, S.; Yang, L.-L.; Ji, S.; Fang, Z.; Zhang, G.; Wang, L.-J.; Zhong, J.-M.; Xiong, Y.; Wang, J.-H.; Huang, S.-Z.; Li, L.-L.; Xiang, R.; Niu, D.; Chen, Y.-C.; Yang, S.-Y., Drug Discovery against Psoriasis: Identification of a New Potent FMS-like Tyrosine Kinase 3 (FLT3) Inhibitor, 1-(4-((1H-Pyrazolo[3,4-d]pyrimidin-4-yl)oxy)-3-fluorophenyl)-3-(5-(tert-butyl)isoxazol-3-yl)urea, That Showed Potent Activity in a Psoriatic Animal Model. J. Med. Chem. 2016, 59, 8293-8305.
17.Li, G.-B.; Huang, L.-Y.; Li, H.; Ji, S.; Li, L.-L.; Yang, S.-Y., Identification of new p300 histone acetyltransferase inhibitors from natural products by a customized virtual screening method. RSC Adv. 2016, 6, 61137-61140.
18.Li, G.-B.; Yang, L.-L.; Yuan, Y.; Zou, J.; Cao, Y.; Yang, S.-Y.; Xiang, R.; Xiang, M., Virtual screening in small molecule discovery for epigenetic targets. Methods 2015, 71, 158-166.
19.Li, G.-B.; Ji, S.; Yang, L.-L.; Zhang, R.-J.; Chen, K.; Zhong, L.; Ma, S.; Yang, S.-Y., LEADOPT: An automatic tool for structure-based lead optimization, and its application in structural optimizations of VEGFR2 and SYK inhibitors. Eur. J. Med. Chem. 2015, 93, 523-538.
20.Yang, L.-L.; Li, G.-B.; Ma, S.; Zou, C.; Zhou, S.; Sun, Q.-Z.; Cheng, C.; Chen, X.; Wang, L.-J.; Feng, S.; Li, L.-L.; Yang, S.-Y., Structure–activity relationship studies of pyrazolo [3, 4-d] pyrimidine derivatives leading to the discovery of a novel multikinase inhibitor that potently inhibits FLT3 and VEGFR2 and evaluation of its activity against acute myeloid leukemia in vitro and in vivo. J. Med. Chem. 2013, 56, 1641-1655.
21.Li, G.-B.; Yang, L.-L.; Xu, Y.; Wang, W.-J.; Li, L.-L.; Yang, S.-Y., A combined molecular docking-based and pharmacophore-based target prediction strategy with a probabilistic fusion method for target ranking. J. Mol. Graphics Modell. 2013, 44, 278-285.
22.Li, G.-B.; Yang, L.-L.; Wang, W.-J.; Li, L.-L.; Yang, S.-Y., ID-Score: a new empirical scoring function based on a comprehensive set of descriptors related to protein–ligand interactions. J. Chem. Inf. Model. 2013, 53, 592-600.
23.Yang, L.-L.; Li, G.-B.; Yan, H.-X.; Sun, Q.-Z.; Ma, S.; Ji, P.; Wang, Z.-R.; Feng, S.; Zou, J.; Yang, S.-Y., Discovery of N6-phenyl-1H-pyrazolo [3, 4-d] pyrimidine-3, 6-diamine derivatives as novel CK1 inhibitors using common-feature pharmacophore model based virtual screening and hit-to-lead optimization. Eur. J. Med. Chem. 2012, 56, 30-38.
24.Li, G.-B.; Yang, L.-L.; Feng, S.; Zhou, J.-P.; Huang, Q.; Xie, H.-Z.; Li, L.-L.; Yang, S.-Y., Discovery of novel mGluR1 antagonists: a multistep virtual screening approach based on an SVM model and a pharmacophore hypothesis significantly increases the hit rate and enrichment factor. Bioorg. Med. Chem. Lett. 2011, 21, 1736-1740
2.Yang, L.-L.; Xu, W.; Yan, J.; Su, H.-L.; Yuan, C.; Li, C.; Zhang, X.; Yu, Z.-J.; Yan, Y.-H.; Yu, Y.; Chen, Q.; Wang, Z.; Li, L.; Qian, S.*; Li, G.-B.* Crystallographic and SAR analyses reveal the high requirements needed to selectively and potently inhibit SIRT2 deacetylase and decanoylase. MedChemComm 2019, 10, 164-168.
3.Yang, L.-L.; Wang, H.-L.; Zhong, L.; Yuan, C.; Liu, S.-Y.; Yu, Z.-J.; Liu, S.; Yan, Y.-H.; Wu, C.; Wang, Y.; Wang, Z.; Yu, Y.; Chen, Q.*; Li, G.-B.*, X-ray crystal structure guided discovery of new selective, substrate-mimicking sirtuin 2 inhibitors that exhibit activities against non-small cell lung cancer cells. Eur. J. Med. Chem. 2018, 155, 806-823.
4.Liu, S.; Jing, L.; Yu, Z.-J.; Wu, C.; Zheng, Y.; Zhang, E.; Chen, Q.; Yu, Y.; Guo, L.; Wu, Y.*; Li, G.-B.*, ((S)-3-Mercapto-2-methylpropanamido)acetic acid derivatives as metallo-β-lactamase inhibitors: Synthesis, kinetic and crystallographic studies. Eur. J. Med. Chem. 2018, 145, 649-660.
5.Zhang, C.; Pu, Y.-c.; Yu, Z.-J.; Wu, C.-y.; Brem, J.; McDonough, M. A.; Schofield, C. J.; Li, G.-B.*; Wu, Y.*, Rh(iii)-Catalyzed directed C-H carbenoid coupling reveals aromatic bisphosphonates inhibiting metallo- and Serine-β-lactamases. Organic Chemistry Frontiers 2018, 5, 1288-1292.
6.Yu, Z.-J.; Zhang, C.; Li, J.-L.; Liu, Y.-Z.; Yu, X.-L.; Guo, L.; Li, G.-B.*; Wu, Y.*, Rh(III)-Catalyzed, 1,2,3-Triazole-Assisted Directed C-H Coupling with Diazo Diphosphonates. Tetrahedron Letters 2018, 59, 2816-2819.
7.Yu, Z.-J.; Liu, S.; Zhou, S.; Li, H.; Yang, F.; Yang, L.-L.; Wu, Y.; Guo, L.; Li, G.-B.*, Virtual target screening reveals rosmarinic acid and salvianolic acid A inhibiting metallo- and serine-β-lactamases. Bioorg. Med. Chem. Lett. 2018, 28, 1037-1042.
8.Yang, Z.; Zhang, Y.; Chen, X.; Li, W.; Li, G.-B.*; Wu, Y.*, Total Synthesis and Evaluation of B-Homo Palmatine and Berberine Derivatives as p300 Histone Acetyltransferase Inhibitors. European Journal of Organic Chemistry 2018, 2018, 1041-1052.
9.Zhou, S.#; Li, G.-B.#; Luo, L.; Zhong, L.; Chen, K.; Li, H.; Jiang, X.-J.; Fu, Q.; Long, X.; Bao, J.-k., Structure-based discovery of new maternal embryonic leucine zipper kinase inhibitors. Organic & Biomolecular Chemistry 2018, 16, 1489-1495. (co-first author)
10.Liu, S.; Ji, S.; Yu, Z.-J.; Wang, H.-L.; Cheng, X.; Li, W.-J.; Jing, L.; Yu, Y.; Chen, Q.; Yang, L.-L.; Li, G.-B.*; Wu, Y.*, Structure-based discovery of new selective small-molecule sirtuin 5 inhibitors. Chemical Biology & Drug Design 2018, 91, 257-268.
11.Yang, L.; Ma, X.; He, Y.; Yuan, C.; Chen, Q.; Li, G.B.*; Chen, X.*, Sirtuin 5: a review of structure, known inhibitors and clues for developing new inhibitors. Sci. China Life Sci. 2017, 60, 249-256.
12.Wang, H.-L.; Liu, S.; Yu, Z.-J.; Wu, C.; Cheng, L.; Wang, Y.; Chen, K.; Zhou, S.; Chen, Q.; Yu, Y.*; Li, G.-B.*, Interactions between sirtuins and fluorogenic small-molecule substrates offer insights into inhibitor design. RSC Adv. 2017, 7, 36214-36222.
13.Li, G.-B.*; Yu, Z.-J.; Liu, S.; Huang, L.-Y.; Yang, L.-L.; Lohans, C. T.; Yang, S.-Y., IFPTarget: A Customized Virtual Target Identification Method Based on Protein–Ligand Interaction Fingerprinting Analyses. J. Chem. Inf. Model. 2017, 57, 1640-1651.
14.Li, G.-B.; Brem, J.; Lesniak, R.; Abboud, M. I.; Lohans, C. T.; Clifton, I. J.; Yang, S.-Y.; Jimenez-Castellanos, J.-C.; Avison, M. B.; Spencer, J.; McDonough, M. A.; Schofield, C. J., Crystallographic analyses of isoquinoline complexes reveal a new mode of metallo-β-lactamase inhibition. Chem. Commun. 2017, 53, 5806-5809.
15.Li, G.-B.; Abboud, M. I.; Brem, J.; Someya, H.; Lohans, C. T.; Yang, S.-Y.; Spencer, J.; Wareham, D. W.; McDonough, M. A.; Schofield, C. J., NMR-filtered virtual screening leads to non-metal chelating metallo-β-lactamase inhibitors. Chem. Sci. 2017, 8, 928-937.
16.Li, G.-B.; Ma, S.; Yang, L.-L.; Ji, S.; Fang, Z.; Zhang, G.; Wang, L.-J.; Zhong, J.-M.; Xiong, Y.; Wang, J.-H.; Huang, S.-Z.; Li, L.-L.; Xiang, R.; Niu, D.; Chen, Y.-C.; Yang, S.-Y., Drug Discovery against Psoriasis: Identification of a New Potent FMS-like Tyrosine Kinase 3 (FLT3) Inhibitor, 1-(4-((1H-Pyrazolo[3,4-d]pyrimidin-4-yl)oxy)-3-fluorophenyl)-3-(5-(tert-butyl)isoxazol-3-yl)urea, That Showed Potent Activity in a Psoriatic Animal Model. J. Med. Chem. 2016, 59, 8293-8305.
17.Li, G.-B.; Huang, L.-Y.; Li, H.; Ji, S.; Li, L.-L.; Yang, S.-Y., Identification of new p300 histone acetyltransferase inhibitors from natural products by a customized virtual screening method. RSC Adv. 2016, 6, 61137-61140.
18.Li, G.-B.; Yang, L.-L.; Yuan, Y.; Zou, J.; Cao, Y.; Yang, S.-Y.; Xiang, R.; Xiang, M., Virtual screening in small molecule discovery for epigenetic targets. Methods 2015, 71, 158-166.
19.Li, G.-B.; Ji, S.; Yang, L.-L.; Zhang, R.-J.; Chen, K.; Zhong, L.; Ma, S.; Yang, S.-Y., LEADOPT: An automatic tool for structure-based lead optimization, and its application in structural optimizations of VEGFR2 and SYK inhibitors. Eur. J. Med. Chem. 2015, 93, 523-538.
20.Yang, L.-L.; Li, G.-B.; Ma, S.; Zou, C.; Zhou, S.; Sun, Q.-Z.; Cheng, C.; Chen, X.; Wang, L.-J.; Feng, S.; Li, L.-L.; Yang, S.-Y., Structure–activity relationship studies of pyrazolo [3, 4-d] pyrimidine derivatives leading to the discovery of a novel multikinase inhibitor that potently inhibits FLT3 and VEGFR2 and evaluation of its activity against acute myeloid leukemia in vitro and in vivo. J. Med. Chem. 2013, 56, 1641-1655.
21.Li, G.-B.; Yang, L.-L.; Xu, Y.; Wang, W.-J.; Li, L.-L.; Yang, S.-Y., A combined molecular docking-based and pharmacophore-based target prediction strategy with a probabilistic fusion method for target ranking. J. Mol. Graphics Modell. 2013, 44, 278-285.
22.Li, G.-B.; Yang, L.-L.; Wang, W.-J.; Li, L.-L.; Yang, S.-Y., ID-Score: a new empirical scoring function based on a comprehensive set of descriptors related to protein–ligand interactions. J. Chem. Inf. Model. 2013, 53, 592-600.
23.Yang, L.-L.; Li, G.-B.; Yan, H.-X.; Sun, Q.-Z.; Ma, S.; Ji, P.; Wang, Z.-R.; Feng, S.; Zou, J.; Yang, S.-Y., Discovery of N6-phenyl-1H-pyrazolo [3, 4-d] pyrimidine-3, 6-diamine derivatives as novel CK1 inhibitors using common-feature pharmacophore model based virtual screening and hit-to-lead optimization. Eur. J. Med. Chem. 2012, 56, 30-38.
24.Li, G.-B.; Yang, L.-L.; Feng, S.; Zhou, J.-P.; Huang, Q.; Xie, H.-Z.; Li, L.-L.; Yang, S.-Y., Discovery of novel mGluR1 antagonists: a multistep virtual screening approach based on an SVM model and a pharmacophore hypothesis significantly increases the hit rate and enrichment factor. Bioorg. Med. Chem. Lett. 2011, 21, 1736-1740
