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Profile: Greg Cuny

Greg Cuny
Greg Cuny, Ph.D.
Assistant Professor of Medicinal Chemistry
Department of Pharmacological and Pharmaceutical Sciences
Science and Research Building 2
3455 Cullen Blvd., Room 549A
Houston, TX 77204-5037

713-743-1274 (Voice)
713-743-1229 (Fax)


Ph.D. in Organic Chemistry, Massachusetts Institute of Technology, Cambridge, Mass.

B.S. in Chemistry, Grove City College, Grove City, Penn.

Research Interests

The research interest of our lab is in the field of medicinal chemistry. The primary goal of our research is to develop in vivo pharmacology probes to study novel therapeutic approaches to treat diseases.

Currently, we are studying several classes of alkaloids and disulfide containing cyclic peptides. The natural and non-natural products generated are then screened for biological activity in assays related to various therapeutic areas.

The lab is also involved in several collaborative projects related to pharmacological probe development. One of these projects aims to design selective inhibitors of inosine-5’-monophosphate dehydrogenase (IMPDH) from the protozoan parasites Cryptosporidium parvum, which are potential bio-warfare agents and major causes of diarrhea and malnutrition. This project also has expanded to include other microorganisms that may be susceptible to selective IMPDH inhibition.

Another project aims to design subtype selective inhibitors of activin-like kinase 2 (ALK2). This target has been implicated in a variety of diseases, including bone and cardiovascular diseases. Finally, another project aims to design selective inhibitors receptor interacting kinase 2 and 3 (RIPK2 and RIPK3), which may be involved in a variety of acute and chronic conditions, including inflammatory diseases.


  • PHAR 4330 Medicinal Chemistry I (2014 – present)
  • PCOL 6345 Drug Design and Discovery (2013 – present)
  • PHAR 4134 Medicinal Functional Group Analysis (2013– present)
  • PHAR 5197 Medicinal Chemistry Research (2014 – present)
  • PHAR 4330 Pharmaceutics I (2014)


  • Yu, P.B.; Cuny, G.D.; Bloch, K.D.; Peterson, R.T.; Hong, C.C. Inhibitors of the BMP signaling pathway. US 9,045,484, 2015.
  • Hedstrom, L.K.; Cuny, G.D.; Gollapalli, D.R.; Striepen, B.; Gorla, S.K.; Kavitha, M. Compounds and methods for treating mammalian gastrointestinal microbial infections. US 8,969,342, 2015.
  • Qiao, L.; Glicksman, M.; Gainer, T.; Lo, D.C.; Stein, R.L.;, Choi, S.; Cuny, G.D. Inhibiting Eph B-3 kinase. US 8,927,545, 2015.
  • Edge, A.; Jeon, S.J-. Seyb, K.; Glicksman, M.; Qiao, L.; Cuny, G.D. Compounds that enhance Atoh1 expression. US 8,859,597, 2014.
  • Raines, D.E.; Cotton, J.F.; Forman, S.A.; Miller, K.W.; Husain, S.S.; Cuny, G.D. Etomidate analogues that do not inhibit adrenocortical steroid synthesis. US 8,765,973, 2014.
  • Cuny, G.D.; Jagtap, P.; Yuan, J.; Degterev, A. Inhibitors of cellular necrosis. US 8,741,942, 2014.
  • Cuny, G.D.; Teng, X.; Yuan, J.; Degterev, A.; Porco, Jr., J.A. Heterocyclic inhibitors of necroptosis. US 8,658,689, 2014.
  • Yu, P.B.; Cuny, G.D.; Bloch, K.D.; Peterson, R.T.; Hong, C.C. Inhibitors of the BMP signaling pathway. US 8,507,501, 2013.
  • Yuan, J.; Degterev, A.; Junichi, H.; Cuny, G.D.; Jagtap, P. Tricyclic necrostatin compounds. US 8,324,262, 2012.
  • Cuny, G.D.; Teng, X.; Yuan, J.; Degterev, A. Heterocyclic inhibitors of necroptosis. US 8,278,344, 2012.
  • Edge, A.; Jeon, S.-J.; Seyb, K.; Glicksman, M.; Qiao, L.; Cuny, G.D. Compounds that enhance Atoh1 expression. US 8,188,131, 2012.
  • Cuny, G.D.; Jagtap, P.; Yuan, J.; Degterev, A. Inhibitors of cellular necrosis. US 8,143,300, 2012.

Selected Publications

Makowska-Grzyska, M.; Kim, Y.; Gorla, S.K.; Wei, Y.; Mandapati, K.; Zhang, M.; Maltseva, N.; Modi, G.; Boshoff, H.I.; Gu, M.; Aldrich, C.; Cuny, G.D.; Hedstrom, L; Joachimiak, A. Structures of Mycobacterium tuberculosis IMPDH in complexes with substrates, products and antitubercular compounds. PLoS Biol. 2015, accepted.

Canning, P.; Ruan, Q.; Schwerd, T.; Hrdinka, M.; Maki, J.L.; Saleh, D.; Suebsuwong, C.; Ray, S.; Brennan, P.E.; Cuny, G.D.; Uhlig, H.H.; Gyrd-Hansen, M.; Degterev, A.; Bullock, A.N. Inflammatory signaling by NOD-RIPK2 is inhibited by clinically-relevant type II kinase inhibitors. Chem Biol. 2015, accepted.

Lang, C.A.; Ray, S.S.; Liu, M.; Singh, A.K.; Cuny, G.D. Discovery of LRRK2 inhibitors using sequential in silico joint pharmacophore space (JPS) and ensemble docking. Bioorg. Med. Chem. Lett. 2015, 25, 2713 – 2719.

Ku, A.F.; Cuny, G.D. Synthetic Studies of 7-Oxygenated Aporphine Alkaloids: Preparation of (–)-Oliveroline, (–)-Nornuciferidine and Derivatives. Org. Lett. 2015, 17, 1134 – 1137.

Najjar, M.; Suebsuwong, C.; Ray, S.S.; Thapa, R.; Maki, J.L.; Nogusa, S.; Shah, S.; Saleh, D.; Gough, P.J.; Bertin, J.; Yuan, J.; Balachandran, S.; Cuny, G.D.; Degterev, A. Structure guided design of potent and selective ponatinib-based hybrid inhibitors for RIPK1. Cell Rep. 2015, 10, 1850-60.

Kim, Y.; Makowska-Grzyska, M.; Gorla, S.K.; Gollapalli, D.R.; Cuny, G.D.; Joachimiak, A.; Hedstrom, L. Structure of Cryptosporidium IMP dehydrogenase bound to an inhibitor with in vivo antiparasitic activity. Acta Cryst. F 2015, 71, 531–538.

Takahashi, K.; Kong, Q.; Lin, Y.; Stouffer, N.; Schulte, D.A.; Lai, L.; Liu, Q.; Chang, L.-C.; Dominguez, S.; Xing, X.; Cuny, G.D.; Hodgetts, K.J.; Glicksman, M.A.; Lin, C.-L.G. Restored Glial Glutamate Transporter EAAT2 Function as a Potential Therapeutic Approach for Alzheimer’s Disease. J. Exp. Med. 2015, 212, 319-32.

Sun, Z.; Khan, J.; Makowska-Grzyska, M.; Zhang, M.; Cho, J.H.; Suebsuwong, C.; Vo, P.; Gollapalli, D.R.; Kim, Y.; Joachimiak, A.; Hedstrom, H.; Cuny, G.D. Synthesis, in vitro evaluation and co-crystal structure of 4-oxo-[1]benzopyrano[4,3-c]pyrazole Cryptosporidium parvum inosine 5’-monophosphate dehydrogenase (CpIMPDH) inhibitors. J. Med. Chem. 2014, 57, 10544–10550.

Mohedas, A.H.; Wang, Y.; Sanvitale, C.E.; Canning, P.; Choi, S.; Xing, X.; Bullock, A.N.; Cuny, G.D.; Yu, P.B. Structure-activity relationship of 3,5-diaryl-2-aminopyridine ALK2 inhibitors reveals unaltered binding affinity for fibrodysplasia ossificans progressiva causing mutants. J. Med. Chem. 2014, 57, 7900-7915.

Mandapati, K.; Gorla, S.K.; House, A.L.; McKenney, E.S.; Zhang, M.; Rao, S.N.; Gollapalli, D.R.; Mann, B.J.; Goldberg, J.B.; Cuny, G.D.; Glomski, I.J.; Hedstrom, L. Repurposing Cryptosporidium inosine 5’-monophosphate dehydrogenase inhibitors as potential antibacterial agents. ACS Med Chem Lett. 2014, 5, 846 - 850.

Xu, J.; Chatterjee, M.; Baguley, T.D.; Brouillette, J.; Kurup, P.; Ghosh, D.; Kanyo, J.; Zhang, Y.; Seyb, K.; Ononenyi, C.; Foscue, E.; Anderson, G.M.; Gresack, J.; Cuny, G.D.; Glicksman, M.A.; Greengard, P.; Lam, T.T.; Tautz, L; Nairn, A.C.; Ellman, J.A.; Lombroso, P.J. Inhibitor of the Tyrosine Phosphatase STEP Reverses Cognitive Deficits in a Mouse Model of Alzheimer’s Disease. PLoS Biol. 2014, 12:e1001923.

Pytel, D.; Seyb, K.; Liu, M.; Concannon, J.; Huang, M.; Cuny, G.D.; Diehl, J.A.; Glicksman, M.A. Enzymatic characterization of ER-stress dependent kinase, PERK, and development of a mechanism based high-throughput screen for identification of PERK inhibitors. J. Biomol. Screen. 2014, 19, 1024-1034.

Kong, Q.; Chang, L.-C.; Takahashi, K.; Liu, Q.; Schulte, D.A.; Lai, L.; Ibabao, B.; Lin, Y.; Stouffer, N.; Mukhopadhyay, C.D.; Xing, X.; Seyb, K.I.; Cuny, G.D.; Glicksman, M.A.; Lin, C.-L. G. Neuroprotection in ALS and epilepsy mouse models with a small molecule activator of glutamate transporter EAAT2 translation. J. Clin. Inv. 2014, 124, 1255-67.

Gorla, S.K.; McNair, N.N.; Yang, G.; Gao, S.; Hu, M.; Jala, V.R.; Haribabu, B.; Striepen, B; Cuny, G.D.; Mead, J.R.; Hedstrom, L. Validation of IMP dehydrogenase inhibitors in a mouse model of cryptosporidiosis. Antimicrob. Agents Chemother. 2014, 58, 1603-14.

Mistry, H.; Hsieh, G.; Buhrlage, S.; Huang, M.; Park, E.; Cuny, G.D.; Galinsky, I.; Stone, R.; Gray, N.; D’Andrea, A.D.; Parmar, K. Small molecule inhibitors of USP1 target ID1 degradation in leukemic cells. Mol. Cancer Ther. 2013, 12, 2651 – 2662.

Zhang, X.; Hermandez, I.; Rei, D.; Mair, W.; Laha, J.K.; Cornwell, M.E.; Cuny, G.D.; Tsai, L.H.; Steen, J.A.; Kosik, K.S. J Biol Chem. 2013, 288, 22042 – 22056.

Wang, X.; Cuny, G.D.; Noël, T. A Mild, One-Pot Stadler–Ziegler Synthesis of Arylsulfides Facilitated by Photoredox Catalysis in Batch and Continuous-Flow. Angew. Chem. Int. Ed. 2013, 52, 7860 – 7864.

Mohedas, A.H.; Xing, X.; Armstrong, K.; Bullock, A.N.; Cuny, G.D.; Yu, P.B. Development of an ALK2-biased BMP type I receptor kinase inhibitor. ACS Chem. Biol. 2013, 8, 1291 – 1302.

Cherry, J.J.; Osman, E.Y.; Evans, M.C.; Choi, S.; Xing, X.; Cuny, G.D.; Glicksman, M.A.; Lorson, C.L.; Androphy, E.J. Enhancement of SMN protein levels in a mouse model of spinal muscular atrophy using novel drug-like compounds. EMBO Mol. Med. 2013, 5, 1103 – 1118.

Gorla, S.K.; Kavitha, M.; Zhang, M.; Chin, J.E.W.; Liu, X.; Striepen, B.; Makowska-Grzyska, M,; Kim, Y.; Joachimiak, A.; Hedstrom, L.; Cuny, G.D. Optimization of benzoxazole-based inhibitors of Cryptosporidium parvum inosine 5’-monophosphate dehydrogenase. J. Med. Chem. 2013, 56, 4028 – 4043.

Barolo, S.M.; Wang, Y.; Rossi, R.A.; Cuny, G.D. Synthesis of pyrido[1,2-a]benzimidazoles by photo-stimulated C-N bond formation via SRN1 reactions. Tetrahedron 2013, 69, 5487 – 5494.

Sanvitale, C.E.; Kerr, G.; Chaikuad, A.; Ramel, M.-C.; Mohedas, A.H.; Reichert, S.; Wang, Y.; Triffitt, J.T.; Cuny, G.D.; Yu, P.B.; Hill, C.S.; Bullock, A.N. A new class of small molecule inhibitor of BMP signaling. PLoS One 2013, e62721.

Maki, J.L.; Brazell; J.T.; Teng, X.; Cuny, G.D.; Degterev, A. Expression and purification of active human receptor interacting protein 1 kinase using a baculovirus system. Protein Expres. Purif. 2013, 89, 156 – 161.

Liu, M.; Bender, S.; Cuny, G.D.; Sherman, W.; Glicksman, M.A.; Ray, S. Type II kinase inhibitors show an unexpected inhibition mode against Parkinson’s disease-linked LRRK2 mutant G2019S. Biochemistry 2013, 52, 1725 – 1736.

McNamara, C.R.; Ahuja, R.; Osafo-Addo, A.; Barrows, D.; Kettenbach, A.; Skidan, I.; Teng, X.; Cuny, G.D.; Gerber, S.; Degterev, A. Interplay of Akt and JNK signaling downstream from RIP1 kinase controls necroptosis and autocrine TNF synthesis. PLoS One 2013, 8, e56576.

Johnson, C.R.; Gorla, S.K.; Kavitha, M.; Zhang, M.; Liu, X.; Striepen, B.; Mead, J.; Cuny, G.D.; Hedstrom, L. Phthalazinone inhibitors of inosine-5’-monophosphate dehydrogenase from Cryptosporidium parvum. Bioorg. Med. Chem. Lett. 2013, 23, 1004 – 1007.

Research Grants and Contracts 

National Institutes of Health
American Heart Association


  • American Chemical Society

Editorial Appointments & Professional Service

Journal Reviewer (ad hoc): Bioorganic and Medicinal Chemistry Letters, European Journal of Medicinal Chemistry, Journal of Organic Chemistry, Journal of the American Chemical Society, Journal of Natural Products, Tetrahedron, Tetrahedron Letters, Organic Letters, Synlett, Molecular Diversity and Nature Chemical Biology.