Luolab in Sichuan University

Where we are
Dr. Youfu Luo
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Youfu Luo, Ph.D.

             Professor in State Key Laboratory of Biotherapy, West China Hospital, Sichuan University.


Education:

            1999   Bachelor, China University of Geosciences. Wuhan.

            2002   Master, China University of Geosciences. Wuhan.

            2009   Ph.D. Sichuan University. Chengdu.


Funding:

        National Natural Science Foundation of China (No. 81473253)

      National Natural Science Foundation of China (No. 81973368)

      National Mega-projects of China for Innovative Drugs (2012ZX09103-101-036)

      National Mega-projects of China for Innovative Drugs (2019ZX09721001-001)   

Research field
Design and synthesis of small molecule drugs  
At present, we  find novel scaffold compounds as small molecule drugs of specific biological targets based on rational and classical methods of drug design, and rapidly obtain target compounds by microwave, click chemistry and  the conventional methods. The structure-activity relationship will be studied to discover a candidate compound for preclinical studies.
Biomolecular crystallography
Structure of biological targets plays an important role in drug design. Based on the new biological target, the molecular cloning, protein expression and purification are carried out for the crystallographic study. In combination with structure-based drug design (SBDD) and fragment-based drug design (FBDD), the bioactive molecules will be found, and the mode of interaction with target will be illuminated.
Pharmacology
The pharmacology of preclinical candidate (PCC) is evaluated systematically, involving antibacterial drug pharmacology, neuropsychopharmacology and genome research, related to several commonly experimental technologies and analysis methods, such as chemical proteomics, structural biology, molecular biology, cell biology and ethology.
Publications

1. Zhang, J.; Luo, B.;  Sui, J.;  Qiu, Z.; Huang, J.;  Yang, T.; Luo, Y., IMP075 targeting ClpP for colon cancer therapy in vivo and in vitro. Biochem Pharmacol 2022, 204, 115232.

2. Zhang, J.; Qiao, W.; Luo, Y., Mitochondrial quality control proteases and their modulation for cancer therapy. Med Res Rev 2022.

3. Huang, J.; Zhang, J.;  Luo, B.;  Qiao, W.; Qiu, Z.;  Song, R.;  Dai, Z.; Sui, J.;  Xu, X.;  Ruan, S.; Li, C.;  Luo, Y.; Yang, T., Discovery of a Novel Series of Imipridone Compounds as Homo sapiens Caseinolytic Protease P Agonists with Potent Antitumor Activities In Vitro and In Vivo. J Med Chem 2022, 65 (11), 7629-7655.

4. Song, R.; Qiao, W.;  He, J.;  Huang, J.; Luo, Y.; Yang, T., Proteases and Their Modulators in Cancer Therapy:Challenges and Opportunities. J Med Chem 2021, 64 (6), 2851-287













   Yang J, Zhang L, He X, Gou X, Zong Z, Luo Y. In vitro and in vivo enhancement effect of glabridin on the antibacterial activity of colistin, against multidrug resistant Escherichia coli strains. Phytomedicine. 2024 Jul 25;130:155732. doi: 10.1016/j.phymed.2024.155732.

   Liu S, Sui J, Luo B, Zhang J, Xiang X, Yang T, Luo Y, Liu J. Discovery of 5-(Piperidin-4-yl)-1,2,4-oxadiazole Derivatives as a New Class of Human Caseinolytic Protease P Agonists for the Treatment of Hepatocellular Carcinoma. J Med Chem. 2024 Jul 11;67(13):10622-10642. doi: 10.1021/acs.jmedchem.4c00080.

   Zhou Y, Qiu Z, Dong B, Yang Y, Wang Q, Yang T, Zhang J, He Z, Zhang X, Li J, Ni X, Zeng J, Luo Y. Integrating computational and experimental approaches in discovery and validation of MmpL3 pore domain inhibitors for specific labelling of Mycobacterium tuberculosis. Int J Biol Macromol. 2024 Aug 30;279(Pt 2):135212. doi: 10.1016/j.ijbiomac.2024.135212.

   Zhang J, Qiu Z, Liu S, Huang J, Luo B, Sui J, Dai Z, Xiang X, Yang T, Luo Y. Discovery of a Novel Series of Homo sapiens Caseinolytic Protease P Agonists for Colorectal Adenocarcinoma Treatment via ATF3-Dependent Integrated Stress Response. J Med Chem. 2024 Feb 22;67(4):2812-2836. doi: 10.1021/acs.jmedchem.3c01950.

   Xiang X, Dai Z, Luo B, Zhao N, Liu S, Sui J, Huang J, Zhou Y, Gu J, Zhang J, Yang T, Bao R, Luo Y. Rational Design of a Novel Class of Human ClpP Agonists through a Ring-Opening Strategy with Enhanced Antileukemia Activity. J Med Chem. 2024 Apr 25;67(8):6769-6792. doi: 10.1021/acs.jmedchem.4c00338.

   Huang Z, Gou X, Hang X, Shi T, Yang J, Liu Y, He X, Li J, Quan K, Bi H, Luo Y. Design, Synthesis, and Biological Evaluation of 5-(5-Iodo-2-isopropyl-4-methoxyphenoxy)pyrimidine-2,4-diamine (AF-353) Derivatives as Novel DHFR Inhibitors against Staphylococcus aureus. J Med Chem. 2024 Mar 28;67(6):4757-4781. doi: 10.1021/acs.jmedchem.3c02355.

   Zhang L, Yang J, Xu X, Zhang J, Qiu Z, Ju Y, Luo B, Liu Y, Gou X, Sui J, Chen B, Wang Y, Tao T, He L, Yang T, Luo Y. Discovery and Optimization of Novel SaFabI Inhibitors as Specific Therapeutic Agents for MRSA Infection. J Med Chem. 2024 Jun 27;67(12):10096-10134. doi: 10.1021/acs.jmedchem.4c00320.

   Jiang Y, Xu X, Fan D, Liu P, Zhou M, Cheng M, Huang J, Luo Y, Guo Y, Yang T. Advancing Tumor-Targeted Chemo-Immunotherapy: Development of the CAR-M-derived Exosome-Drug Conjugate. J Med Chem. 2024 Aug 22;67(16):13959-13974. doi: 10.1021/acs.jmedchem.4c00753.

Wang Z, He L, Fan Z, Luo Y. Patenting perspective of modulators of ClpP endopeptidase: 2019-present. Expert Opin Ther Pat. 2024 Sep 16:1-12. doi: 10.1080/13543776.2024.2404233.

   Li L, Liu S, Luo Y. Application of covalent modality in proximity-induced drug pharmacology: Early development, current strategy, and feature directions. Eur J Med Chem. 2024 May 5;271:116394. doi: 10.1016/j.ejmech.2024.116394.

   He X, Gou X, Fan D, Yang J, Fu X, Luo Y, Yang T. Repurposing TAK875 as a novel STAT3 inhibitor for treating inflammatory bowel disease. Biochem Pharmacol. 2024 Jan;219:115957. doi: 10.1016/j.bcp.2023.115957.

   Li C, Tian X, Huang Z, Gou X, Yusuf B, Li C, Gao Y, Liu S, Wang Y, Yang T, Liu Z, Sun Q, Zhang T, Luo Y. Structure-Activity Relationship of Novel Pyrimidine Derivatives with Potent Inhibitory Activities against Mycobacterium tuberculosis. J Med Chem. 2023 Feb 23;66(4):2699-2716. doi: 10.1021/acs.jmedchem.2c01647.

   Yang Y, Zhao N, Xu X, Zhou Y, Luo B, Zhang J, Sui J, Huang J, Qiu Z, Zhang X, Zeng J, Bai L, Bao R, Luo Y. Discovery and Mechanistic Study of Novel Mycobacterium tuberculosis ClpP1P2 Inhibitors. J Med Chem. 2023 Dec 28;66(24):16597-16614. doi: 10.1021/acs.jmedchem.3c01054.

   Liu P, Jiang Y, Jiao L, Luo Y, Wang X, Yang T. Strategies for the Discovery of Oxazolidinone Antibacterial Agents: Development and Future Perspectives. J Med Chem. 2023 Oct 26;66(20):13860-13873. doi: 10.1021/acs.jmedchem.3c01040.

   Xu X, Zhang L, Yang T, Qiu Z, Bai L, Luo Y. Targeting caseinolytic protease P and its AAA1 chaperone for tuberculosis treatment. Drug Discov Today. 2023 Mar;28(3):103508. doi: 10.1016/j.drudis.2023.103508.

   He X, Gou X, Fan D, Yang J, Fu X, Luo Y, Yang T. Repurposing TAK875 as a novel STAT3 inhibitor for treating inflammatory bowel disease. Biochem Pharmacol. 2024 Jan;219:115957. doi: 10.1016/j.bcp.2023.115957.

   Zhou X, Gou K, Xu J, Jian L, Luo Y, Li C, Guan X, Qiu J, Zou J, Zhang Y, Zhong X, Zeng T, Zhou Y, Xiao Y, Yang X, Chen W, Gao P, Liu C, Zhou Y, Tao L, Liu X, Cen X, Chen Q, Sun Q, Luo Y, Zhao Y. Discovery and Optimization of Novel hDHODH Inhibitors for the Treatment of Inflammatory Bowel Disease. J Med Chem. 2023 Nov 9;66(21):14755-14786. doi: 10.1021/acs.jmedchem.3c01365.

  Zhang J, Qiao W, Luo Y. Mitochondrial quality control proteases and their modulation for cancer therapy. Med Res Rev. 2023 Mar;43(2):399-436. doi: 10.1002/med.21929.

Yang J, Zhang L, Qiao W, Luo Y. Mycobacterium tuberculosis: Pathogenesis and therapeutic targets. MedComm (2020). 2023 Sep 4;4(5):e353. doi: 10.1002/mco2.353.

   Sui J, Qiao W, Xiang X, Luo Y. Epigenetic changes in Mycobacterium tuberculosis and its host provide potential targets or biomarkers for drug discovery and clinical diagnosis. Pharmacol Res. 2022 May;179:106195. doi: 10.1016/j.phrs.2022.106195.


Patents

1.Yang, Tao; Xu, Xin; Luo, Youfu; Peng, Xian. Nitrofuran methyleneoxy dihydroindole piperidine propionamide derivative as oral antibacterial agent.From Faming Zhuanli Shenqing (2021), CN 112174943 A 20210105.Language: Chinese, Database: CAPLUS

2.Xu, Xin; Yang, Tao; Peng, Xian; Luo, Youfu. Naphthalene compounds as bactericides and application in preparing products for preventing and treating oral bacteria thereof.From Faming Zhuanli Shenqing (2021), CN 112194588 A 20210108. Language: Chinese, Database: CAPLUS

3.Luo, Youfu; Yang, Tao; Sang, Zitai. Bacterial ribosome inhibitor screening method, and bacterial ribosome inhibitors.From Faming Zhuanli Shenqing (2020), CN 111808922 A 20201023.Language: Chinese, Database: CAPLUS
4.Luo, Youfu; Geng, Funeng. Small-​molecule compound against Staphylococcus, and its preparing method and application.From Faming Zhuanli Shenqing (2020), CN 111320618 A 20200623.Language: Chinese, Database: CAPLUS
5.Luo, Youfu; Yang, Tao. Antibacterial application of 4-​fluoro-​2-​methylindole compound.From Faming Zhuanli Shenqing (2020), CN 111166750 A 20200519.Language: Chinese, Database: CAPLUS
6.Luo, Youfu; Zhang, Tianyu. Pyrimidine small-​molecule compound and its application in preparation of antimycobacterial drug.From Faming Zhuanli Shenqing (2019), CN 110563656 A 20191213.Language: Chinese, Database: CAPLUS
7.Luo, Youfu; Zhang, Tianyu. Small-​molecule compd., preparation method thereof and application thereof to prepare drugs against Mycobacterium bovis such as drug-​resistant Mycobacterium tuberculosis.From Faming Zhuanli Shenqing (2019), CN 109988157 A 20190709.Language: Chinese, Database: CAPLUS
8. Luo, Youfu; Yang, Tao; Wei, Yuquan. Indole-​2-​one compounds and application thereof in antibacterial.From Faming Zhuanli Shenqing (2018), CN 108586434 A 20180928.Language: Chinese, Database: CAPLUS
9. Luo, Youfu; Yang, Tao; Wei, Yuquan.Application of ceritinib in antimicrobial agent.From Faming Zhuanli Shenqing (2018), CN 108420822 A 20180821.Language: Chinese, Database: CAPLUS
10. Luo, Youfu; Yang, Tao; Wei, Yuquan. Application of indole-​2-​ketone compounds in persister resistance.From Faming Zhuanli Shenqing (2018), CN 108420820 A 20180821.Language: Chinese, Database: CAPLUS
Contact information

        The State Key Lab of Biotherapy, Sichuan University No.17 Renmin S Rd, 3rd Section. Chengdu, China, 610041

        Email: luo_youfu@scu.edu.cn