Dr. Leng’s research focuses on new drug R&D and mechanism study for type 2 diabetes and metabolic disease. The anti-diabetic drug efficacy evaluation platform, which includes more than 50 kinds of assays were set up for lead compounds discovery and preclinical pharmacodynamic evaluation. Using the different kinds of molecular assays, cell-based assays and type 2 diabetic animal models, dozens of anti-diabetic compounds (synthetic compounds or natural products) were discovered and 19 patents had been applied, included some International patents. Dr. Leng is also interested in the molecular mechanisms underlining type 2 diabetes, with particular, but not exclusive in insulin resistance. Several anti-diabetic lead compounds were used as the probes to investigate the new mechanisms involved in the treatment of metabolic disorder. Dr. Leng had published more than 50 papers in SCI journals, including Diabetes, Diabetologia, Br J Pharmacol and JMC et al. The research has been funded by the National Nature Science Foundation of China, State Key Program of Basic Research of China (973 program), National Science & Technology Major Project “Key New Drug Creation and Manufacturing Program”, EFSD/CDS/Lilly Programme for Collaborative Diabetes Research between China and Europe, Shanghai Rising-Star Foundation, and Science and Technology Commission of Shanghai Municipality.

(2009.01.01 - current)

1. Zou Q, Duan H, Ning M, Liu J, Feng Y, Zhang L, Zhu J, Leng Y*, Shen J * 4-Benzofuranyloxynicotinamide derivatives are novel potent and orally available TGR5 agonists. Eur J Med Chem. 2014 May 13;82C:1-15

2. Deng X, Shen Y, Yang J, He J, Zhao Y, Peng LY, Leng Y*, Zhao QS*. Discovery and structure-activity relationships of ent-Kaurene diterpenoids as potent and selective 11β-HSD1 inhibitors: Potential impact in diabetes. Eur J Med Chem. 2013 Jul;65:403-14

3. Zhu J, Ye Y, Ning M, Mandi A, Feng Y, Zou Q, Kurtan T, Leng Y*, Shen J* Design, Synthesis, and Structure-Activity Relationships of 3,4,5-Trisubstituted 4,5-Dihydro-1,2,4-oxadiazoles as TGR5 Agonists. ChemMedChem. 2013 Jul;8(7):1210-23

4. Duan H, Ning M, Chen X, Zou Q, Zhang L, Feng Y, Zhang L, Leng Y*, Shen J*, Design, Synthesis, and Antidiabetic Activity of 4-Phenoxynicotinamide and 4-Phenoxypyrimidine-5-carboxamide Derivatives as Potent and Orally Efficacious TGR5 Agonists. J Med Chem. 2012，55(23):10475-89

5. Ye N, Xu XT, Li FY, Ning MM, Liu ZQ, Cao YQ, Leng Y*, Zhang A*. Investigation on the oxidation of aryl oxiranylmethanols and the synthesis of 2-aryl-N-thiazolyl-oxirane-2-carboxamides as glucokinase activators. Tetrahedron Letters 53 (2012) 4738–4742

6. Wang YJ, Huang SL, Feng Y, Ning MM, Leng Y*. Emodin, an 11β-hydroxysteroid dehydrogenase type 1 inhibitor, regulates adipocyte function in vitro and exerts anti-diabetic effect in ob/ob mice. Acta Pharmacol Sin. 2012 Sep;33(9):1195-203

7. Liu X, Zhang LN, Feng Y, Zhang L, Qu H, Cao GQ, Leng Y*.Acute and chronic administration of SHR117887, a novel and specific dipeptidyl peptidase-4 inhibitor, improves metabolic control in diabetic rodent models.Acta Pharmacol Sin. 2012 Aug;33(8):1013-22

8. Huang SL, Yu RT, Gong J, Feng Y, Dai YL, Hu F, Hu YH, Tao YD*, Leng Y*. Arctigenin, a natural compound, activates AMP-activated protein kinase via inhibition of mitochondria complex I and ameliorates metabolic disorders in ob/ob mice. Diabetologia. 2012 May;55(5):1469-81

9. Mao W, Ning M, Liu Z, Zhu Q, Leng Y*, Zhang A*.Design, synthesis, and pharmacological evaluation of benzamide derivatives as glucokinase activators. Bioorg Med Chem. 20 (2012) 2982–2991

10. Zhang L, Chen J, Ning M, Zou Q, Leng Y*, Shen J*.Synthesis and evaluation of piperidine urea derivatives as efficacious 11β-hydroxysteroid dehydrogenase type 1 inhibitors in diabetic ob/ob mice. Bioorg Med Chem Lett. 2012 15;22(8):2748-52

11. Simo Mpetga JD, Shen Y, Tane P, Li SF, He HP, Wabo HK, Tene M, Leng Y*, Hao XJ*.Cycloartane and Friedelane Triterpenoids from the Leaves of Caloncoba glauca and Their Evaluation for Inhibition of 11β-Hydroxysteroid Dehydrogenases. J Nat Prod. 2012 Apr 27;75(4):599-604

12. Liu ZQ, Zhu QZ，Li FY，Zhang LN, Leng Y*，Zhang A* N-(5-substituted thiazol-2-yl)-2-aryl-3-(tetrahydro-2H-pyran-4-yl) propanamides as glucokinase activators. Med. Chem. Commun., 2011; 2: 531–535

13. Feng Y, Huang SL, Dou W, Zhang S, Chen JH, Shen Y, Shen JH, Leng Y* Emodin, a natural product, selectively inhibits 11β-hydroxysteroid dehydrogenase type 1 and ameliorates metabolic disorder in diet-induced obese mice. Br J Pharmacol. 2010 ;161(1):113-26

14. Li FY, Zhu QZ, Zhang Y, Feng Y, Leng Y*, Zhang A*. Desgin, synthesis, and pharmacological evaluation of N-(4-mono and 4,5-disubstituted thiazol-2-yl)- 2-aryl-3-(tetrahydro-2H-pyran-4-yl) propanamides as glucokinase activators. Bioorg Med Chem. 2010;18(11):3875–3884

15. Zhang L, Shen Y, Wang F, Leng Y*, Liu JK*. Rare merosesquiterpenoids from basidiomycete Craterellus odoratus and their inhibition of 11beta-hydroxysteroid dehydrogenases. Phytochemistry 2010 Jan ;71(1):100-3

16. Ye YL, Zhou Z, Zou HJ, Shen Y, Xu TF, Tang J, Yin HZ, Chen ML, Leng Y*, Shen JH*. Discovery of novel dual functional agent as PPARgamma agonist and 11beta-HSD1 inhibitor for the treatment of diabetes. Bioorg Med Chem. 2009;17(15):5722-32

17. Zhang X, Zhou Z, Yang HY, Chen JH, Feng Y, Du L, Leng Y*, Shen JH*. 4-(Phenylsulfonamidomethyl)benzamides as potent and selective inhibitors of the 11beta-hydroxysteroid dehydrogenase type 1 with efficacy in diabetic ob/ob mice. Bioorg Med Chem Lett. 2009;19(15):4455-8

18. Zhang L,Li HL, Zhu QZ, Liu J, Chen L, Leng Y*, Jiang HL, Liu H*. Benzamide derivatives as dual-action hypoglycemic agents that inhibit glycogen phosphorylase and activate glucokinase. Bioorg Med Chem. 2009:7301-7312

19. Zhang X, Zhou Y, Shen Y, Du LL, Chen JH, Leng Y*, Shen JH*. Derivatives of (phenylsulfonamido-methyl)nicotine and (phenylsulfonamido-methyl)thiazole as novel 11beta-hydroxysteroid dehydrogenase type 1 inhibitors: synthesis and biological activities in vitro. Acta Pharmacol Sin. 2009; 30:1344-1350

20. Xu D, Sheng Y, Zhou ZY, Liu R, Leng Y*, Liu JK*. Sesquiterpenes from cultures of the basidiomycete Clitocybe conglobata and their 11 beta-hydroxysteroid dehydrogenase inhibitory activity. Chem Pharm Bull (Tokyo). 2009 Apr;57(4):433-5

21. Zhang L, Shen Y, Zhu HJ, Wang F, Leng Y*, Liu JK*. Pentanol derivatives from basidiomycete Catathelasma imperiale and their 11beta-hydroxysteroid dehydrogenases inhibitory activity. J Antibiot (Tokyo). 2009 May;62(5):239-42

22. Yang H, Shen Y, Chen J, Jiang Q, Leng Y*, Shen J*. Structure-based virtual screening for identification of novel 11beta-HSD1 inhibitors. Eur J Med Chem. 2009 Mar;44(3):1167-71