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Minying Cai

Research Professor

Degrees and Appointments

  • Ph.D. 2004 University of Arizona, Biochemistry & Molecular Biophysics
  • Research Assistant 1991-1992 Shanghai Institute of Materia Medica, Shanghai Institute of Biochemistry, Chinese Academy of Sciences
  • Research Associate Professor 1992-1997 Shanghai Research Center of Biotechnology, Chinese Academy of Sciences
  • Associate Professor 1997-1999 Shanghai Research Center of Biotechnology, Chinese Academy of Sciences

Awards and Honors

  • The highest award from China Ministry of Science and Technology for “Progress in Science & Technology”. (1997.3) Award Given to the Project on Studies of Transgenic Plants (Major Role).
  • The highest award from China Ministry of Agriculture for the work of transgenic plant project ‘Genetic Engineering of Potato Cultivars for Resistance to Bacteria’. (1996.7) Individual Award Given to the Project.
  • Travel award from American Peptide Society (2001)
  • V.J. Hruby Fellowship Award in Peptide Research for “Those who succeed in science do so by hard work and the excellence of their ideas”. (2005.6)
  • Galileo Circle Copernicus Awardees at the University of Arizona (2018).
 

Peptides and proteins play a vital role in almost every cellular process in living organisms. Our research discovers and determines structural information on peptides and proteins to design drugs to more effectively treat human disease. We are working on projects at the interface of chemical biology, molecular pharmacology and molecular biology within the areas of:1. Structure based drug design and synthesis of GPCR ligands, including developing selective human melanocortin receptors (hMCRs) ligands; 2. Developing novel biophysics tools for molecular imaging; novel molecular biomarker; high-throughput screening system, etc. 3. Exploiting novel scaffold via computational chemistry for small molecule therapeutics for energy balance and cancer study; 4. Exploring the novel physiological functions of melanocortin system involved. In collaboration with other investigators worldwide, we aim to identify and develop molecule modulators of GPCRs for the therapeutic treatment of melanoma, metabolic and CNS disorders.

 

File selective_publication.docx

 

 

1.   Eerola, K.; Virtanen, S.; Vahatalo, L.; Ailanen, L.; Cai, M.; Hruby, V.; Savontaus, M.; Savontaus, E., Hypothalamic gamma-melanocyte stimulating hormone gene delivery reduces fat mass in male mice. J Endocrinol 2018.

2.   Mowlazadeh Haghighi, S.; Zhou, Y.; Dai, J.; Sawyer, J. R.; Hruby, V. J.; Cai, M., Replacement of Arg with Nle and modified D-Phe in the core sequence of MSHs, Ac-His-D-Phe-Arg-Trp-NH2, leads to hMC1R selectivity and pigmentation. Eur J Med Chem 2018, 151, 815-823.

3.   Merlino, F.; Zhou, Y.; Cai, M.; Carotenuto, A.; Yousif, A. M.; Brancaccio, D.; Di Maro, S.; Zappavigna, S.; Limatola, A.; Novellino, E.; Grieco, P.; Hruby, V. J., Development of Macrocyclic Peptidomimetics Containing Constrained alpha,alpha-Dialkylated Amino Acids with Potent and Selective Activity at Human Melanocortin Receptors. J Med Chem 2018, 61 (9), 4263-4269.

4.  Durek, T.; Cromm, P. M.; White, A. M.; Schroeder, C. I.; Kaas, Q.; Weidmann, J.; Ahmad Fuaad, A.; Cheneval, O.; Harvey, P. J.; Daly, N. L.; Zhou, Y.; Dellsen, A.; Osterlund, T.; Larsson, N.; Knerr, L.; Bauer, U.; Kessler, H.; Cai, M.; Hruby, V. J.; Plowright, A. T.; Craik, D. J., Development of Novel Melanocortin Receptor Agonists Based on the Cyclic Peptide Framework of Sunflower Trypsin Inhibitor-1. J Med Chem 2018, 61 (8), 3674-3684.

5.   Zhou, Y.; Mowlazadeh Haghighi, S.; Zoi, I.; Sawyer, J. R.; Hruby, V. J.; Cai, M., Design of MC1R Selective gamma-MSH Analogues with Canonical Amino Acids Leads to Potency and Pigmentation. J Med Chem 2017, 60 (22), 9320-9329.

6.   Cai, M.; Marelli, U. K.; Mertz, B.; Beck, J. G.; Opperer, F.; Rechenmacher, F.; Kessler, H.; Hruby, V. J., Structural Insights into Selective Ligand-Receptor Interactions Leading to Receptor Inactivation Utilizing Selective Melanocortin 3 Receptor Antagonists. Biochemistry-Us 2017, 56 (32), 4201-4209.

7.   Zhou, Y.; Cai, M., Novel approaches to the design of bioavailable melanotropins. Expert Opin Drug Discov 2017, 12 (10), 1023-1030.

8.   Rinne, P.; Rami, M.; Nuutinen, S.; Santovito, D.; van der Vorst, E. P. C.; Guillamat-Prats, R.; Lyytikainen, L. P.; Raitoharju, E.; Oksala, N.; Ring, L.; Cai, M.; Hruby, V. J.; Lehtimaki, T.; Weber, C.; Steffens, S., Melanocortin 1 Receptor Signaling Regulates Cholesterol Transport in Macrophages. Circulation 2017, 136 (1), 83-97.

9.   Cai, M.; Hruby, V. J., Design of cyclized selective melanotropins. Biopolymers 2016, 106 (6), 876-883.

10. Cai, M.; Hruby, V. J., The Melanocortin Receptor System: A Target for Multiple Degenerative Diseases. Curr Protein Pept Sci 2016, 17 (5), 488-96.

11. Carotenuto, A.; Merlino, F.; Cai, M.; Brancaccio, D.; Yousif, A. M.; Novellino, E.; Hruby, V. J.; Grieco, P., Discovery of Novel Potent and Selective Agonists at the Melanocortin-3 Receptor. J Med Chem 2015, 58 (24), 9773-8.

12. Shukla, C.; Koch, L. G.; Britton, S. L.; Cai, M.; Hruby, V. J.; Bednarek, M.; Novak, C. M., Contribution of regional brain melanocortin receptor subtypes to elevated activity energy expenditure in lean, active rats. Neuroscience 2015, 310, 252-67.

13. Cai, M.; Marelli, U. K.; Bao, J.; Beck, J. G.; Opperer, F.; Rechenmacher, F.; McLeod, K. R.; Zingsheim, M. R.; Doedens, L.; Kessler, H.; Hruby, V. J., Systematic Backbone Conformational Constraints on a Cyclic Melanotropin Ligand Leads to Highly Selective Ligands for Multiple Melanocortin Receptors. J Med Chem 2015, 58 (16), 6359-67.

14. Van der Poorten, O.; Feher, K.; Buysse, K.; Feytens, D.; Zoi, I.; Schwartz, S. D.; Martins, J. C.; Tourwe, D.; Cai, M.; Hruby, V. J.; Ballet, S., Azepinone-Containing Tetrapeptide Analogues of Melanotropin Lead to Selective hMC4R Agonists and hMC5R Antagonist. Acs Med Chem Lett 2015, 6 (2), 192-7.

15. Cai, M.; Stankova, M.; Muthu, D.; Mayorov, A.; Yang, Z.; Trivedi, D.; Cabello, C.; Hruby, V. J., An unusual conformation of gamma-melanocyte-stimulating hormone analogues leads to a selective human melanocortin 1 receptor antagonist for targeting melanoma cells. Biochemistry-Us 2013, 52 (4), 752-64.

16. Rinne, P.; Nordlund, W.; Heinonen, I.; Penttinen, A. M.; Saraste, A.; Ruohonen, S. T.; Makela, S.; Vahatalo, L.; Kaipio, K.; Cai, M.; Hruby, V. J.; Ruohonen, S.; Savontaus, E., alpha-Melanocyte-stimulating hormone regulates vascular NO availability and protects against endothelial dysfunction. Cardiovasc Res 2013, 97 (2), 360-8.

17. Hruby, V. J.; Cai, M.; Nyberg, J.; Muthu, D., Approaches to the rational design of selective melanocortin receptor antagonists. Expert Opin Drug Discov 2011, 6 (5), 543-57.

18. Mayorov, A. V.; Cai, M.; Palmer, E. S.; Tanaka, D. K.; Cain, J. P.; Dedek, M. M.; Tan, B.; Trivedi, D.; Hruby, V. J., Cyclic lactam hybrid alpha-MSH/Agouti-related protein (AGRP) analogues with nanomolar range binding affinities at the human melanocortin receptors. Bioorg Med Chem Lett 2011, 21 (10), 3099-102.

19. Cai, M.; Liu, Z.; Qu, H.; Fan, H.; Zheng, Z.; Hruby, V. J., Utilize conjugated melanotropins for the earlier diagnosis and treatment of melanoma. Eur J Pharmacol 2011, 660 (1), 188-93.

20. Hruby, V. J.; Cai, M.; Cain, J.; Nyberg, J.; Trivedi, D., Design of novel melanocortin receptor ligands: multiple receptors, complex pharmacology, the challenge. Eur J Pharmacol 2011, 660 (1), 88-93.

21. Mayorov, A. V.; Cai, M.; Palmer, E. S.; Liu, Z.; Cain, J. P.; Vagner, J.; Trivedi, D.; Hruby, V. J., Solid-phase peptide head-to-side chain cyclodimerization: discovery of C(2)-symmetric cyclic lactam hybrid alpha-melanocyte-stimulating hormone (MSH)/agouti-signaling protein (ASIP) analogues with potent activities at the human melanocortin receptors. Peptides 2010, 31 (10), 1894-905.

22. Doedens, L.; Opperer, F.; Cai, M.; Beck, J. G.; Dedek, M.; Palmer, E.; Hruby, V. J.; Kessler, H., Multiple N-methylation of MT-II backbone amide bonds leads to melanocortin receptor subtype hMC1R selectivity: pharmacological and conformational studies. J Am Chem Soc 2010, 132 (23), 8115-28.

23. Juni, A.; Cai, M.; Stankova, M.; Waxman, A. R.; Arout, C.; Klein, G.; Dahan, A.; Hruby, V. J.; Mogil, J. S.; Kest, B., Sex-specific mediation of opioid-induced hyperalgesia by the melanocortin-1 receptor. Anesthesiology 2010, 112 (1), 181-8.

24. Yang, Y.; Hruby, V. J.; Chen, M.; Crasto, C.; Cai, M.; Harmon, C. M., Novel binding motif of ACTH analogues at the melanocortin receptors. Biochemistry-Us 2009, 48 (41), 9775-84.

25. Cai, M.; Nyberg, J.; Hruby, V. J., Melanotropins as drugs for the treatment of obesity and other feeding disorders: potential and problems. Curr Top Med Chem 2009, 9 (6), 554-63.

26. Qu, H.; Cai, M.; Mayorov, A. V.; Grieco, P.; Zingsheim, M.; Trivedi, D.; Hruby, V. J., Substitution of arginine with proline and proline derivatives in melanocyte-stimulating hormones leads to selectivity for human melanocortin 4 receptor. J Med Chem 2009, 52 (12), 3627-35.

27. Hruby, V. J.; Cai, M.; Dedek, M.; Qu, H.; Palmer, E.; Mayorov, A.; Trivedi, D.; Tsaprailis, G.; Yang, Y., Peptide and non-peptide mimetics utilize different pathways for signal transduction. Adv Exp Med Biol 2009, 611, 305-7.

28. Min, B. J.; Mayorov, A. V.; Cai, M.; Palmer, E.; Hruby, V. J., Design and parallel synthesis of new bicyclic small molecules for targeting the melanocortin receptors. Adv Exp Med Biol 2009, 611, 187-8.

29. Yang, Y.; Cai, M.; Chen, M.; Qu, H.; McPherson, D.; Hruby, V.; Harmon, C. M., Key amino acid residues in the melanocortin-4 receptor for nonpeptide THIQ specific binding and signaling. Regul Pept 2009, 155 (1-3), 46-54.

30. Chen, M.; Cai, M.; McPherson, D.; Hruby, V.; Harmon, C. M.; Yang, Y., Contribution of the transmembrane domain 6 of melanocortin-4 receptor to peptide [Pro5, DNal (2')8]-gamma-MSH selectivity. Biochem Pharmacol 2009, 77 (1), 114-24.

31. Grieco, P.; Cai, M.; Liu, L.; Mayorov, A.; Chandler, K.; Trivedi, D.; Lin, G.; Campiglia, P.; Novellino, E.; Hruby, V. J., Design and microwave-assisted synthesis of novel macrocyclic peptides active at melanocortin receptors: discovery of potent and selective hMC5R receptor antagonists. J Med Chem 2008, 51 (9), 2701-7.

32. Lee, M.; Kim, A.; Conwell, I. M.; Hruby, V.; Mayorov, A.; Cai, M.; Wardlaw, S. L., Effects of selective modulation of the central melanocortin-3-receptor on food intake and hypothalamic POMC expression. Peptides 2008, 29 (3), 440-7.

33. Mayorov, A. V.; Cai, M.; Palmer, E. S.; Dedek, M. M.; Cain, J. P.; Van Scoy, A. R.; Tan, B.; Vagner, J.; Trivedi, D.; Hruby, V. J., Structure-activity relationships of cyclic lactam analogues of alpha-melanocyte-stimulating hormone (alpha-MSH) targeting the human melanocortin-3 receptor. J Med Chem 2008, 51 (2), 187-95.

34. Lee, Y. S.; Agnes, R. S.; Cain, J. P.; Kulkarni, V.; Cai, M.; Salibay, C.; Ciano, K.; Petrov, R.; Mayorov, A.; Vagner, J.; Trivedi, D.; Davis, P.; Ma, S. W.; Lai, J.; Porreca, F.; Vardanyan, R.; Hruby, V. J., Opioid and melanocortin receptors: do they have overlapping pharmacophores? Biopolymers 2008, 90 (3), 433-8.

35. Hruby, V. J.; Cai, M.; Cain, J. P.; Mayorov, A. V.; Dedek, M. M.; Trivedi, D., Design, synthesis and biological evaluation of ligands selective for the melanocortin-3 receptor. Curr Top Med Chem 2007, 7 (11), 1107-19.

36. Chen, M.; Cai, M.; Aprahamian, C. J.; Georgeson, K. E.; Hruby, V.; Harmon, C. M.; Yang, Y., Contribution of the conserved amino acids of the melanocortin-4 receptor in [corrected] [Nle4,D-Phe7]-alpha-melanocyte-stimulating [corrected] hormone binding and signaling. J Biol Chem 2007, 282 (30), 21712-9.

37. Grieco, P.; Cai, M.; Han, G.; Trivedi, D.; Campiglia, P.; Novellino, E.; Hruby, V. J., Further structure-activity studies of lactam derivatives of MT-II and SHU-9119: their activity and selectivity at human melanocortin receptors 3, 4, and 5. Peptides 2007, 28 (6), 1191-6.

38. Ballet, S.; Mayorov, A. V.; Cai, M.; Tymecka, D.; Chandler, K. B.; Palmer, E. S.; Rompaey, K. V.; Misicka, A.; Tourwe, D.; Hruby, V. J., Novel selective human melanocortin-3 receptor ligands: use of the 4-amino-1,2,4,5-tetrahydro-2-benzazepin-3-one (Aba) scaffold. Bioorg Med Chem Lett 2007, 17 (9), 2492-8.

39. Ying, J.; Gu, X.; Cai, M.; Dedek, M.; Vagner, J.; Trivedi, D. B.; Hruby, V. J., Design, synthesis, and biological evaluation of new cyclic melanotropin peptide analogues selective for the human melanocortin-4 receptor. J Med Chem 2006, 49 (23), 6888-96.

40. Cai, M.; Varga, E. V.; Stankova, M.; Mayorov, A.; Perry, J. W.; Yamamura, H. I.; Trivedi, D.; Hruby, V. J., Cell signaling and trafficking of human melanocortin receptors in real time using two-photon fluorescence and confocal laser microscopy: differentiation of agonists and antagonists. Chem Biol Drug Des 2006, 68 (4), 183-93.

41. Cain, J. P.; Mayorov, A. V.; Cai, M.; Wang, H.; Tan, B.; Chandler, K.; Lee, Y.; Petrov, R. R.; Trivedi, D.; Hruby, V. J., Design, synthesis, and biological evaluation of a new class of small molecule peptide mimetics targeting the melanocortin receptors. Bioorg Med Chem Lett 2006, 16 (20), 5462-7.

42. Mayorov, A. V.; Han, S. Y.; Cai, M.; Hammer, M. R.; Trivedi, D.; Hruby, V. J., Effects of macrocycle size and rigidity on melanocortin receptor-1 and -5 selectivity in cyclic lactam alpha-melanocyte-stimulating hormone analogs. Chem Biol Drug Des 2006, 67 (5), 329-35.

43. Mayorov, A. V.; Cai, M.; Chandler, K. B.; Petrov, R. R.; Van Scoy, A. R.; Yu, Z.; Tanaka, D. K.; Trivedi, D.; Hruby, V. J., Development of cyclic gamma-MSH analogues with selective hMC3R agonist and hMC3R/hMC5R antagonist activities. J Med Chem 2006, 49 (6), 1946-52.

44. Grieco, P.; Cai, M.; Mayorov, A. V.; Trivedi, D.; Hruby, V. J., Structure-activity studies of new melanocortin peptides containing an aromatic amino acid at the N-terminal position. Peptides 2006, 27 (2), 472-81.

45. Cai, M.; Mayorov, A. V.; Ying, J.; Stankova, M.; Trivedi, D.; Cabello, C.; Hruby, V. J., Design of novel melanotropin agonists and antagonists with high potency and selectivity for human melanocortin receptors. Peptides 2005, 26 (8), 1481-5.

46. Cai, M.; Mayorov, A. V.; Cabello, C.; Stankova, M.; Trivedi, D.; Hruby, V. J., Novel 3D pharmacophore of alpha-MSH/gamma-MSH hybrids leads to selective human MC1R and MC3R analogues. J Med Chem 2005, 48 (6), 1839-48.

47. Cai, M.; Stankova, M.; Pond, S. J.; Mayorov, A. V.; Perry, J. W.; Yamamura, H. I.; Trivedi, D.; Hruby, V. J., Real time differentiation of G-protein coupled receptor (GPCR) agonist and antagonist by two photon fluorescence laser microscopy. J Am Chem Soc 2004, 126 (23), 7160-1.

48. Cai, M.; Cai, C.; Mayorov, A. V.; Xiong, C.; Cabello, C. M.; Soloshonok, V. A.; Swift, J. R.; Trivedi, D.; Hruby, V. J., Biological and conformational study of beta-substituted prolines in MT-II template: steric effects leading to human MC5 receptor selectivity. J Pept Res 2004, 63 (2), 116-31.

49. Balse-Srinivasan, P.; Grieco, P.; Cai, M.; Trivedi, D.; Hruby, V. J., Structure-activity relationships of gamma-MSH analogues at the human melanocortin MC3, MC4, and MC5 receptors. Discovery of highly selective hMC3R, hMC4R, and hMC5R analogues. J Med Chem 2003, 46 (23), 4965-73.

50. Balse-Srinivasan, P.; Grieco, P.; Cai, M.; Trivedi, D.; Hruby, V. J., Structure-activity relationships of novel cyclic alpha-MSH/beta-MSH hybrid analogues that lead to potent and selective ligands for the human MC3R and human MC5R. J Med Chem 2003, 46 (17), 3728-33.

51. Hruby, V. J.; Cai, M.; Grieco, P.; Han, G.; Kavarana, M.; Trivedi, D., Exploring the stereostructural requirements of peptide ligands for the melanocortin receptors. Ann N Y Acad Sci 2003, 994, 12-20.

52. Grieco, P.; Lavecchia, A.; Cai, M.; Trivedi, D.; Weinberg, D.; MacNeil, T.; Van der Ploeg, L. H.; Hruby, V. J., Structure-activity studies of the melanocortin peptides: discovery of potent and selective affinity antagonists for the hMC3 and hMC4 receptors. J Med Chem 2002, 45 (24), 5287-94.

53. Kavarana, M. J.; Trivedi, D.; Cai, M.; Ying, J.; Hammer, M.; Cabello, C.; Grieco, P.; Han, G.; Hruby, V. J., Novel cyclic templates of alpha-MSH give highly selective and potent antagonists/agonists for human melanocortin-3/4 receptors. J Med Chem 2002, 45 (12), 2644-50.

 

 

 

 

 

CancerObesity & DiabetesPainneurodegenerative diseaseHighthroughtput ScreenGPCRMelanocortin SystemDrug Design & DiscoveryAmino Acid and Peptide Synthesis