罗海彬 博士、海南大学二级教授、药学院院长,目前为国家重大人才工程获得者(2021年)、政府特殊津贴专家(2023)、 海南省B类人才(2021年)、广东医学-(2018年)、国家重点研发计划首席科学家(2017年)、广东省珠江学者(2016 年)、国家-(2015年)。2021年11月荣获国际超算“戈登贝尔”提名奖(药学界首次入围该奖,戈登贝尔奖是国际上高性能 计算应用领域的最高学术奖项),2019年荣获中国化学会青年计算化学家奖和2014年荣获中国药学会施维雅青年药物化学奖。20 20年11月荣获民革中央的“抗击新冠肺炎疫情新冠肺炎疫情先进个人”称号和广东民革省委会的“抗击新冠肺炎疫情先进个人”称号。1999年7月本科 毕业于厦门大学,2002年7月硕士毕业于厦门大学、2005年10月博士毕业于香港浸会大学,2006年12月-2020年12月工作于中山大学药 学院,先后担任副教授、教授和副院长。2021年1月起任海南大学药学院首任院长,筹建海南大学新药筛选与评价平台。多年来 主要从事新药研发工作(包括药物设计、有机合成、药物筛选和靶标验证等),已创制新冠肺炎治疗药物双嘧达莫和2个临床前 候选药物(已实现了成果转化)。
E-Mail:hbluo@hainanu.edu.cn, 20817504@qq.com
1.教育背景
1995.09 - 2002.07 | 厦门大学化学系,学士、硕士 |
2002.10 - 2005.12 | 香港浸会大学化学系,博士 |
2.教学情况
主讲计算机辅助药物设计
3.科研情况
面向突发重大公共疫情和国家/军队的重大需求,聚焦于药物设计新方法、肺部炎症性疾病、皮肤类疾病新药研发,构建了基于自由能微扰的药/靶结合强度预测等核心算法,实现部分方法的新突破及国产化,成功应用于新冠肺炎、缺氧性肺动脉高压和肺纤维化等肺部炎症性疾病新药研发。创制了新冠肺炎治疗药物双嘧达莫、两个靶向磷酸二酯酶PDE临床前候选新药1607和LW33(两个均实现成果转化)、十个PDEs成药性候选分子。在Cell、Nat Sci Rev、PNAS、Acta Pharm Sin B、J Med Chem等国内外权威期刊发表150多篇论文;申请专利30多项;获批1项国家重点研发计划和6项国自然基金,科研经费超过3000万。
4.研究领域
药物设计新方法、PDE靶向药物
5.社会兼职
中国化学会计算机化学专业委员会委员
广东药学会药物化学专业委员会副主委兼秘书长
6.代表性项目
国家自然科学基金面上项目:新型磷酸二酯酶PDE1选择性抑制剂的发现、成药性优化和抗肺纤维化作用研究,2021.01-2024.12
国家自然科学基金面上项目:特异性识别磷酸二酯酶PDE8的黄嘌呤类衍生物:设计、抗血管性痴呆活性及作用机制研究,2019.01-2022.12
国家重点研发计划:基于E 级高性能计算生物医药应用软件系统研制及应用 2017.07-2020.12
国自然优秀青年基金,药物设计与发现,2016.01-2018.12
广东省“珠江学者”特聘教授项目,2016.10-2021.09
广州市科技机会科学研究重点项目,抗肺动脉高压首创药物2058对磷酸二酯酶PDE5变构位点的调节机制、结构优化和成药性研究,2019.04-2022.03,
7.代表性成果
2000年后,在Cell、Natl Sci Rev、PNAS、ACS Nano、ACS Catalysis、Acta Pharm Sin B、J Med Chem等国内外杂志发表论文150多篇(*表示为通讯作者)。
1)Discovery of novel phosphodiesterase-1 inhibitors for curing vascular dementia: Suppression of neuroinflammation by blocking NF-κB transcription regulation and activating cAMP/CREB axis. Zhou Q, Le M, Yang Y, Wang W, Huang Y, Wang Q, Tian Y, Jiang M, Rao Y,* Luo, H.-B*., Wu Y.* Acta Pharm. Sin. B. 2023, 13(3): 1180-1191.
2)Structure-based discovery of orally efficient inhibitors via unique interactions with H-pocket of PDE8 for the treatment of vascular dementia. Wu XN, Zhou Q, Huang YD, Xie X, Li Z, Wu Y*, Luo, H.-B*. Acta Pharm. Sin. B. 2022,12(7):3103-3112.
3)Structural Modifications of Nimodipine Lead to Novel PDE1 Inhibitors with Anti-pulmonary Fibrosis Effects. Huang MX, Tian YJ, Han C, Liu RD, Xie X, Yuan Y, Yang YY, Li Z, Chen J*, Luo, H.-B*., Wu Y.* J. Med. Chem. 2022, 65(12):8444-8455.
4)Wu D, Zheng X, Liu R, Li Z, Jiang Z, Zhou Q, Huang Y, Wu XN, Zhang C, Huang YY*, Luo, H.-B*. Free energy perturbation (FEP)-guided scaffold hopping. Acta Pharm. Sin. B. 2022,12(3):1351-1362.
5)Xie G, Wu XN, Ling Y, Rui Y, Wu D, Zhou J, Li J, Lin S, Peng Q, Li Z, Wang H*, Luo, H.-B*. A novel inhibitor of N 6-methyladenosine demethylase FTO induces mRNA methylation and shows anti-cancer activities. Acta Pharm. Sin. B. 2022 12(2):853-866.
6)Li, Z.; Li, H.; Yu, K.*; Luo, H.-B*. Perspective of drug design with high-performance computing. Natl. Sci. Rev. 2021, 8(12), nwab105.
7)Huang YY, Deng J, Tian YJ, Liang J, Xie X, Huang Y, Zhu J, Zhu Z, Zhou Q, He X,* Luo H.-B.* Mangostanin Derivatives as Novel and Orally Active Phosphodiesterase 4 Inhibitors for the Treatment of Idiopathic Pulmonary Fibrosis with Improved Safety. J. Med. Chem. 2021, 64(18):13736-13751.
8)Wu Y, Wang Q, Jiang MY, Huang YY, Zhu Z, Han C, Tian YJ, Zhang B, Luo, H.-B*. Discovery of Potent Phosphodiesterase-9 Inhibitors for the Treatment of Hepatic Fibrosis. J. Med. Chem. 2021, 64(13):9537-9549.
9)Guo L, Wei RX, Sun R, Yang Q, Li GJ, Wang LY*, Luo H-B*, Feng M*. "Cytokine-microfactories" recruit DCs and deliver tumor antigens via gap junctions for immunotherapy. J. Control. Release. 2021, 337:417-430.
10)Li, Z.; Li X.; Huang, Y.Y.; Wu, Y.; Liu, R.; Zhou, L.; Lin, Y.; Wu, D.; Zhang, L.; Liu, H.; Xu, X.; Yu, K.; Zhang, Y.; Cui. J*.; Zhan, C.G*.; Wang, X*.; Luo, H.-B*. Identify potent SARS-CoV-2 main protease inhibitors via accelerated free energy perturbation-based virtual screening of existing drugs. Proc. Natl. Acad. Sci. U S A. 2020, 117(44): 27381-27387. 高被引论文。
11)Wu, Y.; Li, Z.; Zhao, Y.S.; Huang, Y.Y.; Jiang, M.Y.; Luo, H.-B*. Therapeutic targets and potential agents for the treatment of COVID-19. Med. Res. Rev. 2021, 41(3):1775-1797.
12)Sun J, Xiao Z, Haider A, Gebhard C, Xu H, Luo H-B, Zhang HT, Josephson L, Wang L, Liang SH. Advances in Cyclic Nucleotide Phosphodiesterase-Targeted PET Imaging and Drug Discovery. J. Med. Chem. 2021, 64(11): 7083-7109.
13)Gao Y, Huang J, Zhou Q, Liu R, Zhang S, Zhang C, Huang YY, Li Z, Huang L, Wu D, Wu Y, Xiao L, Guo L*, Luo H-B.* Discovery of Highly Specific Catalytic-Site-Targeting Fluorescent Probes for Detecting Lysosomal PDE10A in Living Cells. ACS Chem. Biol. 2021, 16(5):857-863.
14)Yang Y, Zhang S, Zhou Q, Zhang C, Gao Y, Wang H, Li Z, Wu D, Wu Y, Huang YY*, Guo L*, Luo H-B.* Discovery of highly selective and orally available benzimidazole-based phosphodiesterase 10 inhibitors with improved solubility and pharmacokinetic properties for treatment of pulmonary arterial hypertension. Acta Pharm. Sin. B. 2020,10(12):2339-2347.
15)Huang, Y.; Wu, X.N.; Zhou, Q.; Wu. Y.; Zheng. D, Li, Z.; Guo, L.; Luo, H.-B*. Rational Design of 2-Chloroadenine Derivatives as Highly Selective Phosphodiesterase 8A Inhibitors. J. Med. Chem. 2020, 63(24): 15852-15863.
16)Zhang T, Lai Z, Yuan S, Huang YY, Dong G, Sheng C*, Ke H*, Luo H.-B.* Discovery of Evodiamine Derivatives as Highly Selective PDE5 Inhibitors Targeting a Unique Allosteric Pocket. J. Med. Chem. 2020, 63(17):9828-9837.
17)Wu Y, Tian YJ, Le ML, Zhang SR, Zhang C, Huang MX, Jiang MY, Zhang B, Luo H-B.* Discovery of Novel Selective and Orally Bioavailable Phosphodiesterase-1 Inhibitors for the Efficient Treatment of Idiopathic Pulmonary Fibrosis. J. Med. Chem. 2020, 63(14): 7867-7879.
18)Jinhao Liang, Yi-You Huang, Qian Zhou, Yuqi Gao, Zhe Li, Deyan Wu, Si Yu, Lei Guo, Zhen Chen, Ling Huang, Steven H Liang, Xixin He*, Ruibo Wu*, Hai-Bin Luo.* Discovery and optimization of α-mangostin derivatives as novel PDE4 inhibitors for the treatment of vascular dementia, J. Med. Chem. 2020, 63, 3370-3380
19)Xiaoyan Liu; Zhe Li; Shuai Liu; Jing Sun; Zhanghua Chen; Min Jiang; Qingling Zhang; Yinghua Wei; Xin Wang; Yi-You Huang; Yinyi Shi; Yanhui Xu; Huifang Xian; Fan Bai; Changxing Ou; Bei Xiong; Andrew M Lew; Jun Cui; Rongli Fang; Hui Huang; Jincun Zhao*; Xuechuan Hong*; Yuxia Zhang*; Fuling Zhou*; Hai-Bin Luo.* Potential therapeutic effects of dipyridamole to the severely ill , patients with COVID-19(12家机构参加本研究)Acta Pharm. Sin. B 2020, 10(7):1205-1215. 高被引论文。
20)Ma, Y.; Ye, Z.; Zhang, C.; Wang, X.; Li, H.W.; Wong, M.S.; Luo, H.-B.*; Xiao, L.* Deep Red Blinking Fluorophore for Nanoscopic Imaging and Inhibition of β-Amyloid Peptide Fibrillation. ACS Nano. 2020 ,14(9):11341-11351.
21)Li Z.; Zhao, Y.; Huifang Zhou, H.; Luo, H-B*.; Zhan, C.G.* Catalytic Roles of Coenzyme Pyridoxal-5′-phosphate (PLP) in PLP-Dependent Enzymes: Reaction Pathway for Methionine-γ-Lyase-Catalyzed l-Methionine Depletion. ACS Catalysis 2020, 10, 2198-2210.
22)Fan Zhang, Tianyue An, Xiaowen Tang, Jiachen Zi*, Hai-Bin Luo*, Ruibo Wu*. Enzyme Promiscuity versus Fidelity in Two Sesquiterpene Cyclases (TEAS versus ATAS). ACS Catalysis 2020, 10, 1470-1484.
23)Li, Z.; Huang, Y.; Wu, Y.; Chen, J.; Wu, D.; Zhan, C.G.*; Luo, H.-B*. Absolute Binding Free Energy Calculation and Design of a Subnanomolar Inhibitor of Phosphodiesterase-10. J. Med. Chem. 2019, 62, 2099-2111.
24)Wu, Y.; Zhou, Q.; Zhang,T.; Li, Z.; Chen, Y.P.; Zhang, P.; Yu, Y.F.; Geng, H.; Tian, Y.J.; Zhang, C.; Wang, Y.; Chen, J.W.*; Chen, Y. *; Luo, H.-B.* Discovery of Potent, Selective, and Orally Bioavailable Inhibitors against Phosphodiesterase-9, a Novel Target for the Treatment of Vascular Dementia. J. Med. Chem. 2019, 62, 4218-4224.
25)Huang, Y.Y.; Yu, Y.; Zhang, C.; Chen, Y.; Zhou, Q.; Li, Z.; Zhou, S.; Li, Z.; Guo, L.; Wu, D.*; Wu, Y.*; Luo, H-B*. Validation of Phosphodiesterase-10 as a Novel Target for Pulmonary Arterial Hypertension via Highly Selective and Subnanomolar Inhibitors. J. Med. Chem. 2019, 62, 3707-3721.
26)Senling Feng; Huifang Zhou; Deyan Wu; Dechong Zheng; Biao Qu; Ruiming; Liu; Chen Zhang; Zhe Li; Ying Xie;* Hai-Bin Luo.* Nobiletin and its derivatives overcome multidrug resistance (MDR) in cancer: total synthesis and discovery of potent MDR reversal agents. Acta Pharm. Sin. B. 2020, 10, 327-343.
27)Wu, D.W.; Huang Y.; Chen, Y.; Huang, Y.; Geng, H.; Zhang, T.; Zhang, C.; Li, Z.; Guo, L.; Chen, J. W.; Luo, L.-B.* Optimization of Chromeno[2,3-c]pyrrol-9(2H)-ones as Highly Potent, Selective, and Orally Bioavailable PDE5 Inhibitors: Structure-Activity Relationship, X-ray Crystal Structure, and Pharmacodynamic Effect on Pulmonary Arterial Hypertension. J. Med. Chem., 2018, 61, 8468-8473.
28)Wu, D.W.; Zhang, T.H.; Chen, Y.; Huang, Y.; Geng, H.; Yu, Y.; Zhang, C., Lai, Z.W.; Wu, Y.; Guo, X.; Chen, J. W.*; Luo, L.-B.* Discovery and Optimization of Chromeno[2,3-c]pyrrol-9(2H)-ones as Novel Selective and Orally Bioavailable Phosphodiesterase 5 Inhibitors for the Treatment of Pulmonary Arterial Hypertension. J. Med. Chem. 2017, 60(15): 6622-6637.
29)Wu, Y.; Li, Z.; Huang, Y.-Y.; Wu, D.Y.; Luo, L.-B.* Novel Phosphodiesterase Inhibitors for Cognitive Improvement in Alzheimer's Disease. J. Med. Chem. 2018, 61 (13), 5467–5483.
30)Wu, X.N.; Huang, Y.D.; Li, J.X.; Yu, Y.F.; Qian, Z.; Zhang, C.; Wu Y*.; Luo H.-B.* Structure-based design, synthesis, and biological evaluation of novel pyrimidinone derivatives as PDE9 inhibitors. Acta Pharm. Sin. B 2018, 8(4), 615-628.
31)Huang, Y.; Liu, X.; Wu, D.; Tang, G.; Lai, Z.; Zheng, X. *; Yin. S. *; Luo, H.-B. * The discovery, complex crystal structure, and recognition mechanism of a novel natural PDE4 inhibitor from Selaginella pulvinata. Biochem. Pharmacol. 2017, 130, 51-59.
32)Zhang, C.; Feng, L.J.; Huang, Y.; Wu, D.; Li, Z.; Zhou, Q.; Wu, Y. *; Luo, H.-B.* Discovery of Novel Phosphodiesterase-2A Inhibitors by Structure-Based Virtual Screening, Structural Optimization, and Bioassay. J. Chem. Inf. Model. 2017, 57, 355-364.
33)Li, Z.; Wu, Y., Feng, L.J.; Wu, R.*; Luo, H.-B.* Ab Initio QM/MM Study Shows a Highly Dissociated SN2 Hydrolysis mechanism for the cGMP-specific phosphodiesterase-5. J. Chem. Theory Comput. 2015, 10, 5448-5457.
34)Shao, Y.X.; Huang, M.; Cui, W.; Feng, L.J.; Wu, Y.; Cai, Y.; Li, Z.; Zhu, X.; Liu, P.; Wan, Y.;* Ke, H.*; Luo, H.-B.* Discovery of a phosphodiesterase-9A inhibitor as a potential hypoglycemic agent. J. Med. Chem. 2014, 57, 10304-130313.
35)Shang, N.N.; Shao, Y.X.; Cai, Y.H.; Guan, M.; Huang, M.; Cui, W.; He, L.; Yu, Y.J.; Huang, L.; Li, Z.; Bu, X. Z.*; Ke, H.*; Luo, H.-B.* Discovery of 3-(4-hydroxybenzyl)-1-(thiophen-2-yl)chromeno[2,3-c]pyrrol-9(2H)-one as a phosphodiesterase-5 inhibitor and its complex crystal structure. Biochem. Pharmacol.2014, 89: 86-98.
36)Huang, Y.Y.; Li, Z.; Cai, Y.H.; Feng, L.J.; Wu, Y.; Li, X.; Luo, H.-B.* The molecular basis for the selectivity of tadalafil toward phosphodiesterase 5 and 6: A modeling study. J. Chem. Inf. Model. 2013, 53, 3044-3053. PMID: 24180640.
37)Li, Z.; Cai, Y.H.; Cheng, Y.K.; Lu, X.; Shao, Y.X.; Li, X.; Liu, M.; Liu, P.; Luo, H.-B.* Identification of novel phosphodiesterase-4D inhibitors prescreened by molecular dynamics-augmented modeling and validated by bioassay. J. Chem. Inf. Model. 2013, 53, 972-981.PMID: 23517293.
38)Meng, F.; Hou, J.; Shao, Y. X.; Wu, P. Y.; Huang, M.; Zhu, X.; Cai, Y. H.; Li, Z.; Xu, J.; Liu, P. Q.; Luo, H.-B.*; Wan, Y.*; Ke, H*. Structure-based discovery of highly selective phosphodiesterase-9A inhibitors and implications for inhibitor design. J. Med. Chem. 2012, 55(19): 8549-8558. PMID: 22985069.
8.荣誉奖励
中国药学会施维雅青年药物化学奖(2014)
中国化学会青年计算化学家奖(2019)
国际超算“戈登贝尔”提名奖(2021)