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Profile: Greg Cuny

Greg Cuny
Greg Cuny, Ph.D.
Associate Professor of Medicinal Chemistry
Interim Assistant Department Chair


Health 2
University of Houston College of Pharmacy
4849 Calhoun Road, Room 7036
Houston, TX 77204-5037

Office: 713-743-1274
Fax: 713-743-1884
gdcuny@uh.edu

Education

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.

Courses

  • 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)

Patents

  • D'Andrea, A.D.; Cuny, G.D.; Stein, R.L.; Glicksman, M.; Case, A.; Xian, J.; Wilson, D.; Huang, M. Small molecule inhibitors of USP1 deubiquitinating enzyme activity. US 9,518,032, 2016.
  • Hedstrom, L.K.; Cuny, G.D.; Gorla, S.K.; Kavitha, M. Compounds and methods for treating mammalian gastrointestinal microbial infections. US 9,447,134, 2016.
  • Edge, A.; Jeon, S.J-. Seyb, K.; Glicksman, M.; Qiao, L.; Cuny, G.D. Compounds that enhance Atoh1 expression. US 9,433,610, 2016.
  • Wolozin, B.; Glicksman, G.; Cuny, G.D.; Boyd, J. Identification of compounds that disperse TDP-43 inclusions. US 9,359,363, 2016.
  • Androphy, E.; Cuny, G.D.; Cherry, J.; Glicksman, M.A. Screening methods for spinal muscular atrophy. US 9,212,209, 2015.
  • 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 9,187,421, 2015.
  • Cohen, D.; Wagle, N.; Cuny, GD.; Xian, J. Glicksman; M.; Stein, R.L.; Shishova; E.Y. Phosphatidylcholine transfer protein inhibitors. US 9,126,938, 2015.
  • 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

Kearney SE, Zahoránszky-Kőhalmi G, Brimacombe KR, Henderson MJ, Lynch C, Zhao T, Wan KK, Itkin Z, Dillon C, Shen M, Cheff DM, Lee TD, Bougie D, Cheng K, Coussens NP, Dorjsuren D, Eastman RT, Huang R, Iannotti MJ, Karavadhi S, Klumpp-Thomas C, Roth JS, Sakamuru S, Sun W, Titus SA, Yasgar A, Zhang YQ, Zhao J, Andrade RB, Brown MK, Burns NZ, Cha JK, Mevers EE, Clardy J, Clement JA, Crooks PA, Cuny GD, Ganor J, Moreno J, Morrill LA, Picazo E, Susick RB, Garg NK, Goess BC, Grossman RB, Hughes CC, Johnston JN, Joullie MM, Kinghorn AD, Kingston DGI, Krische MJ, Kwon O, Maimone TJ, Majumdar S, Maloney KN, Mohamed E, Murphy BT, Nagorny P, Olson DE, Overman LE, Brown LE, Snyder JK, Porco JA Jr, Rivas F, Ross SA, Sarpong R, Sharma I, Shaw JT, Xu Z, Shen B, Shi W, Stephenson CRJ, Verano AL, Tan DS, Tang Y, Taylor RE, Thomson RJ, Vosburg DA, Wu J, Wuest WM, Zakarian A, Zhang Y, Ren T, Zuo Z, Inglese J, Michael S, Simeonov A, Zheng W, Shinn P, Jadhav A, Boxer MB, Hall MD, Xia M, Guha R, Rohde JM. Canvass: A Crowd-Sourced, Natural-Product Screening Library for Exploring Biological Space. ACS Cent Sci. 2018 Dec 26;4(12):1727-1741. doi: 10.1021/acscentsci.8b00747. Epub 2018 Dec 5. PMID: 30648156

Jiang JK, Huang X, Shamim K, Patel PR, Lee A, Wang AQ, Nguyen K, Tawa G, Cuny GD, Yu PB, Zheng W, Xu X, Sanderson P, Huang W. Discovery of 3-(4-sulfamoylnaphthyl)pyrazolo[1,5-a]pyrimidines as potent and selective ALK2 inhibitors. Bioorg Med Chem Lett. 2018 Nov 1;28(20):3356-3362. doi: 10.1016/j.bmcl.2018.09.006. Epub 2018 Sep 6. PMID: 30227946

Ku AF, Cuny GD. Discovery of 7-hydroxyaporphines as conformationally restricted ligands for beta-1 and beta-2 adrenergic receptors. Medchemcomm. 2018 Jan 22;9(2):353-356. doi: 10.1039/c7md00656j. eCollection 2018 Feb 1. PMID: 30108929

Hrdinka M, Schlicher L, Dai B, Pinkas DM, Bufton JC, Picaud S, Ward JA, Rogers C, Suebsuwong C, Nikhar S, Cuny GD, Huber KV, Filippakopoulos P, Bullock AN, Degterev A, Gyrd-Hansen M. Small molecule inhibitors reveal an indispensable scaffolding role of RIPK2 in NOD2 signaling. EMBO J. 2018 Sep 3;37(17). pii: e99372. doi: 10.15252/embj.201899372. Epub 2018 Jul 19. PMID: 30026309

Chacko S, Boshoff HIM, Singh V, Ferraris DM, Gollapalli DR, Zhang M, Lawson AP, Pepi MJ, Joachimiak A, Rizzi M, Mizrahi V, Cuny GD, Hedstrom L. Expanding Benzoxazole-Based Inosine 5'-Monophosphate Dehydrogenase (IMPDH) Inhibitor Structure-Activity As Potential Antituberculosis Agents. J Med Chem. 2018 Jun 14;61(11):4739-4756. doi: 10.1021/acs.jmedchem.7b01839. Epub 2018 May 30. PMID: 29746130

Suebsuwong C, Pinkas DM, Ray SS, Bufton JC, Dai B, Bullock AN, Degterev A, Cuny GD. Activation loop targeting strategy for design of receptor-interacting protein kinase 2 (RIPK2) inhibitors. Bioorg Med Chem Lett. 2018 Feb 15;28(4):577-583. doi: 10.1016/j.bmcl.2018.01.044. Epub 2018 Jan 31. PMID: 29409752

Choi S, Calder AN, Miller EH, Anderson KP, Fiejtek DK, Rietz A, Li H, Cherry JJ, Quist KM, Xing X, Glicksman MA, Cuny GD, Lorson CL, Androphy EA, Hodgetts KJ. Optimization of a series of heterocycles as survival motor neuron gene transcription enhancers. Bioorg Med Chem Lett. 2017 Dec 1;27(23):5144-5148. doi: 10.1016/j.bmcl.2017.10.066. Epub 2017 Oct 26. PMID: 29103974

Gorla SK, Zhang Y, Rabideau MM, Qin A, Chacko S, House AL, Johnson CR, Mandapati K, Bernstein HM, McKenney ES, Boshoff H, Zhang M, Glomski IJ, Goldberg JB, Cuny GD, Mann BJ, Hedstrom L. Benzoxazoles, Phthalazinones, and Arylurea-Based Compounds with IMP Dehydrogenase-Independent Antibacterial Activity against Francisella tularensis. Antimicrob Agents Chemother. 2017 Sep 22;61(10). pii: e00939-17. doi: 10.1128/AAC.00939-17. Print 2017 Oct. PMID:28739786

Cuny, G.D.; Suebsuwong, C.; Ray, S.S. Inosine-5’;-monophosphate dehydrogenase (IMPDH) inhibitors: a patent and scientific literature review (2002-2016). Expert Opin. Ther. Pat. 2017, accepted.

Ku, A.F.; Cuny, G.D. Access to 6a-alkyl aporphines: Synthesis of (±)-N-methylguattescidine. J. Org. Chem. 2016, 81, 10062 – 10070.

Vippila, M.R.; Nikhar, S.; Gracia, A.P.; Cuny, G.D. Divergent approach for the synthesis of gombamide A and derivatives. Org. Lett. 2016, 18, 4726 – 4729.

Vippila, M.R.; Ly, P.K.; Cuny, G.D. Synthesis and anti-proliferative activity evaluation of the disulfide containing cyclic peptide thiochondrilline C and derivatives. J. Nat. Prod. 2015, 78, 2398 – 2404.

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 TNFα 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
The Welch Foundation

Memberships

American Chemical Society

Editorial Appointments & Professional Service

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