Research
Gunda I. Georg Research Group
Gunda I. Georg Research Group
Research in the Georg group continues to discover male non-hormonal contraceptives and anticancer agents. Highly potent and selective RAR-alpha, dual RAR-alpha/gamma, and RAR gamma selective antagonists have been discovered. A second-generation retinoic acid receptor alpha was about 10 times more potent than YCT-529 and has excellent in vivo potency and reversibility of fertility. Studies also continue to discover allosteric and orthosteric kinase inhibitors for CDK2, CDK11, and TSSK1-3 and inhibitors for the testis-specific BET bromodomain. The discovery of sperm motility inhibitors is pursued by targeting three ion channels critical for fertilization: Na,K-ATPase-4, Slo3 and CatSper.
YCT-529, a selective retinoic acid receptor-alpha antagonist discovered in the Georg group, entered a phase 1a clinical trial as the first non-hormonal male contraceptive in the United Kingdom in December 2023. The clinical trial was completed in June 2024, and no safety concerns were observed. A new phase 1b/2a clinical trial was initiated in 2024 in New Zealand.
YCT-529's Chemical Structure
Syeda, S.S., Sánchez, G., McDermott J.P, Cheryala, N., Wong, H., Georg, G.I., Blanco, G. Strategies to Develop Na,K-ATPase Inhibitors as Male Contraceptives. Int J Mol Sci. 2025 Jun 12;26(12):5646. doi: 10.3390/ijms26125646. PMID: 40565109; PMCID: PMC12192727.
Nayyab, S., Gervasi, M.G., Tourzani, D.A., Shamailova, Y., Akizawa, H., Taghavi, M., Cui, W., Fissore, R., Salicioni, A.M., Georg, G.I., Snyder, E., Visconti, P.E. Identification of TSSK1 and TSSK2 as Novel Targets for Male Contraception. Biomolecules. 2025 Apr 18;15(4):601. doi: 10.3390/biom15040601. PMID: 40305308; PMCID: PMC12024862.
Haque, E., Georg, G.I. Medoxomil Prodrug Strategies. J. Med. Chem. 2025 May 8;68(9):9025-9036. doi: 10.1021/acs.jmedchem.4c02967. Epub 2025 Apr 22. PMID: 40261681.
Giarolla, J., Holdaway, K.A., Nazari, M., Aiad, L.K., Sarkar, B., Georg, G.I. Targeting Cyclin-dependent Kinase 2 Interactions with Cyclins and Speedy 1 for Cancer and Male Contraception. Future Med. Chem. 2025 Mar;17(5):607-627. doi: 10.1080/17568919.2025.2463868. Epub 2025 Mar 4. PMID: 40034037; PMCID: PMC11901406.
Jiang, J., Liang, T., Solberg, J., Chan, A., Kalra, P., Shi, R., Pomerantz, W.C.K., Hawkinson, J.E., Schönbrunn, E., Georg, G.I. Macrocyclic Dihydropyridine Analogs as pan-BET BD2-biased Inhibitors. Eur. J. Med. Chem. 2025 Jun 5;290:117504. doi: 10.1016/j.ejmech.2025.117504. Epub 2025 Mar 16. PMID: 40120495; PMCID: PMC11993331.
Shi, R., Wolgemuth, D.J., Georg, G.I. Development of the Retinoic Acid Alpha-specific Antagonists YCT-529 for Male Contraception: A Brief Review. Contraception, 2025 May;145:110809. doi: 10.1016/j.contraception.2024.110809. Epub 2025 Jan 3. PMID: 39756562; PMCID: PMC11993348.
Mannowetz, N., Chung, S.W., Maitra, S., Noman, M.A.A., Wong, H.L., Cheryala, N., Bakshi, A., Wolgemuth, D.J., Georg, G.I. Targeting the Retinoid Signaling Pathway with YCT-529 for Effective and Reversible Oral Contraception in Mice and Primates. Commun. Med. 2025 Mar 13;5(1):68. doi: 10.1038/s43856-025-00752-7. PMID: 40082579; PMCID:
Holdaway, J., Georg, G. An Emerging Target for Male Contraception. Science 2024, 24;384(6698):849-850. doi: 10.1126/science.adp6432. Epub 2024 May 23. PMID: 38781397.
Noman, M.A.A., Cuellar, R.A.D., Kyzer, J., Cheryala, N., Chung, S.S.S., Holth, A.D., Maitra, S., Naqvi, T., Hawkinson, J.E., Schönbrunn, E., Wong, H., Wolgemuth, D.J., Georg, G.I. Strategies for Developing Retinoic Acid Receptor Alpha-Selective Antagonists as Novel Agents for Male Contraception. Eur. J. Med. Chem. 2023, Dec 5;261:115821. doi: 10.1016/j.ejmech.2023.115821. Epub 2023 Sep 25. PMID: 37776573; PMCID:
Shameem, M., Bagherpoor, A.J., Nakhi, A., Dosa, P., Georg, G.I., Kassie, F. Mitochondria-targeted Metformin (mitomet) Inhibits Lung Cancer in Cellular Models and in Mice by Enhancing the Generation of Reactive Oxygen Species. Mol Carcinog. 2023 Nov;62(11):1619-1629. doi: 10.1002/mc.23603. Epub 2023 Jul 4. PMID: 37401866; PMCID: PMC10961008.
Faber, E. B., Tang, J., Roberts, E., Ganeshkumar, S., Sun, L., Wang, N., Rasmussen, D., Majumdar, D., John, K., Yang, A., Khalid, H., Hawkinson, J.E., Levinson, N.M., Schönbrunn, E., Chennathukuzhi, V., Harki. D.A., Georg, G.I. Development of Allosteric and Selective CDK2 Inhibitors for Contraception with Negative Cooperativity to Cyclin Binding. Nat. Commun. 2023 Jun 3;14(1):3213. doi: 10.1038/s41467-023-38732-x. PMID: 37270540; PMCID: PMC10239507.
Kyzer, J., Chung, S.S.S., Noman, M.A.A., Cuellar, R.A.D., Maitra, S., Naqvi, T., Hawkinson, J., Wolgemuth, D. J., Georg, G. I. Investigation of Retinoic Acid Receptor Alpha Antagonist ER50891 and Analogs in vitro for Potency and Selectivity and in vivo Effects of ER50891 on Spermatogenesis. Arch. Pharm. 2023, Jul;356(7):e2300031. doi: 10.1002/ardp.202300031. Epub 2023 May 8. PMID: 37154197.
Faber, E. B., Wang, N., John, K., Sun, L., Burban, D., Khalid, H., Wong, H.L., Francis, R., Tian, D., Hong, W.H., Yang, A., Wang, L., Elsaid, M., Khalid, H., Levinson, N.M., Schönbrunn, E., Hawkinson, J.E., Georg, G. I. Screening Through Lead Optimization of High Affinity, Allosteric Cyclin-dependent Kinase 2 (CDK2) Inhibitors as Male Contraceptives that Reduce Sperm Counts in Mice. J. Med. Chem. 2023 Feb 9;66(3):1928-1940. doi: 10.1021/acs.jmedchem.2c01731. Epub 2023 Jan 26. PMID: 36701569; PMCID: PMC11556300.
2025 C. S. Hamilton Award Lecture, November 6-7, 2025, Department of Chemistry, University of Nebraska, Lincoln, NE.
Keynote, YCT-529 a Male Contraceptive: The Path from Discovery to the Clinic. 2025 Gordon Research Conference on Organic Reactions and Processes Research Conference, July 20-25, Bryant University, Smith Field, Rhode Island.
Plenary Lecture, XXI National Meeting of the Spanish Society of Medicinal Chemistry (SEQT). June 15-18, 2025, Seville, Spain.
Plenary Lecture, Discovery of Kinase Inhibitors and Degraders for Male Contraception. 11th RSC/SCI Symposium on Kinase Inhibitor Design. May 12-13, 2025, Edenborough, UK.
2025 National Contraception Meeting: Male Non-hormonal Contraceptive Projects in the Georg group: An Update. April 29, 2025, Durham, North Carolina.
Targeting Drug-Resistant Breast Cancer with Allosteric Cyclin-dependent Kinase (CDK2) Inhibitors. Breast Cancer SPORE Scientific Series Symposium. Mayo Clinic, Rochester, MN, April 16, 2025.
2025 Bristol-Myers Squibb Lecture: Discovery and Development of a Male Pill by Targeting the Retinoid Signaling Pathway with YCT-529 for Effective, Reversible Oral Contraception. April 4, 2025, Department of Chemistry, University of Pennsylvania, PA.
Plenary Lecture, Development of Allosteric Inhibitors against Cyclin-dependent Kinase 2 (CDK2), Global Trends in Health Technology and Management 2025 (GTHTM-2025), February 15-17, 2025, Global Institute of Pharmaceutical Education and Research (GIPER), Kashipur, India.
Minnesota Department of Health. Sexual and Reproductive Health Services Meeting. Male Contraception: An Update. October 7, 2024, Saint Paul, MN.
International Retinoids Conference VII. FASEB. Discovery of Retinoid Receptor Antagonists for Male Contraception. July 7-11, 2024, Saint Paul, MN.
Fourth International Congress on Male Contraception. Selective Retinoic Acid Receptor Alpha Antagonists. International Consortium for Male Contraception and Population Council. New York, June 6, 2024.
Keynote Lecture Chemistry-Biochemistry-Biology Interface Annual Symposium: Retinoic Acid Receptor Antagonists: Chemistry and Biology, Notre Dame University, South Bend, Indiana, May 16, 2024.
Roland T. Lakey Award. Insights from an Academic Career in Medicinal Chemistry: From Leprosy to Contraception. Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, April 18, 2024.
Roland T. Lakey Award. Discovery and Development of a Male Pill: Are We Finally Getting There? Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, April 18, 2024.
Keynote address. The Male Pill. Are we There Yet? International Symposium on Global Trends in Health, Technology, and Management (GTHTM-2024), Uttarakhand Technical University, India, March 15, 2024.
Sydney Archer Lecture. Discovery and Development of a Male Pill: Are We Finally Getting There? Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Albany, NY, March 12, 2024
Keynote address. Retinoic Acid Receptor Antagonists for Male Non-hormonal Contraception. Keynote. 2nd International Conference: Paradigm Shift in Health Care Profession, University of Swabi, Anbar, Swabi, Pakistan, March 5, 2024.
Syeda, S.; Sanchez, G.; Cheryala, N.; McDermott, J.; Liu, Y.; Hawkinson, J. E. Wong, H.; Blanco, G.; Georg. G. I. Targeting Na,K-ATPase Alpha-4 for Male Contraception. Center for Biomedical Research Seminar Series, Population Council, New York, NY, February 27, 2024.
Syeda, S.; Sanchez, G.; Cheryala, N.; McDermott, J.; Liu, Y.; Hawkinson, J. E. Wong, H.; Blanco, G.; Georg. G. I. Targeting Na,K-ATPase Alpaha-4 for Male Contraception. National Contraception Meeting, Baylor Medical College, Houston, TX, November 13-16, 2023.
The Male Pill: Are We There Yet? 21st International, 1st Inter-Islamic &33rd National Chemistry Conference (CHEMCON23), Islamabad, Pakistan, October 23-25, 2023.
The Male Pill: Are We There Yet? 48th National Organic Chemistry Symposium, July 9-13, 2023, University of Notre Dame.
David Chu Distinguished Lectureship on Drug Discovery, University of Georgia, College of Pharmacy, March 15, 2023. The Male Pill: Are We There Yet?
UW-Madison/WARF Therapeutics Distinguished Lecture in Drug Discovery, University of Wisconsin, Madison, College of Pharmacy, February 10, 2023. Discovery and Development of a Novel Contraceptive for Men.