Stephen Palmer, Associate Professor, Director of Lead Discovery and Development
$300,000 / 2 years Awarded 2019 |
Stephen Palmer, PhDBaylor College of Medicine
Houston, TX About
Stephen Palmer, Ph.D., has 25 years of experience in drug discovery and development in both pharmaceutical discovery groups and entrepreneurial drug discovery start-ups. Prior to joining the Center for Drug Discovery at Baylor College of Medicine, he was a founder of TocopheRx, Inc, and led this small biotech through successful discovery and non-clinical development of a front runner and back-up positive allosteric modulator of the follicle stimulating hormone (FSH) receptor. This compound is as effective as recombinant gonadotropins in rodent granulosa cells and more potent in human granulosa cells, and is orally bioavailable. He was formerly the Global Head of Reproductive Health Research, EMD Serono, and held various positions from Research Director to Site Director of EMD Serono Research Institute in Massachusetts. His experience in contraceptive research began at J&J Pharmaceutical Research & Development, where he pursued discovery of novel non-steroidal contraceptive development efforts. The focus of his efforts at the Baylor College of Medicine, Center for Drug Discovery is to develop novel therapies in therapeutic areas that fall within the expertise present within the Center for Drug Discovery at Baylor College of Medicine that include sub-groups of serine-threonine kinases, G-protein coupled receptors, metabolic enzymes, and proteolytic enzymes. In addition to drug discovery and non-clinical development, he has participated in clinical trial design and post-approval studies for women’s health indications in contraception, infertility and gynecologic inflammation. Our Grant
The Baylor Center for Drug Discovery (CDD) is searching for novel compounds that have potential to evolve into preclinical candidates effective in experimental models of contraception. This current effort is pursuing a highly validated protein, a sperm-specific lactate dehydrogenase enzyme (LDHC), that has been previously shown to be essential for the hypermotility of sperm, a required property of sperm for fertilization of the oocyte. In mouse models where expression of the LDHC gene is deleted, the male mice are infertile. Among a subset of infertile human couples, men that express non-functional LDHC are infertile, confirming the essential role of this enzyme for fertilization and conception. In preliminary efforts, the CDD has identified selective inhibitors of LDHC (relative to LDHA) using their established DEC-Tec drug discovery platform. The overall goal in this funding effort is to bring a compound to the stage of non-clinical development that inhibits LDHC, through depletion of the energy source required for hyperactive motility of sperm, and prevents fertilization and conception in rodent models. Their specific aims are to optimize the affinity and selectivity of LDHC inhibitors to achieve our preclinical target product profile for reducing LDHC enzyme activity, energy available for sperm hyperactivation, and fertilization and conception rates in rodent models of fertility. |
MCI Grantee: Baylor College of Medicine (Dr. Stephen Palmer)
Publications
Teng X, Emmett MJ, Lazar MA, Goldberg E, Rabinowitz JD. Lactate Dehydrogenase C Produces S-2-Hydroxyglutarate in Mouse Testis. ACS Chem Biol. 2016 Sep 16;11(9):2420-7.
Odet F, Gabel S, London RE, Goldberg E, Eddy EM. Glycolysis and mitochondrial respiration in mouse LDHC-null sperm. Biol Reprod. 2013 Apr 18;88(4):95.
Faver JC, Riehle K, Lancia DR Jr, Milbank JBJ, Kollmann CS, Simmons N, Yu Z, Matzuk MM. Quantitative Comparison of Enrichment from DNA-Encoded Chemical Library Selections. ACS Comb Sci. 2019 Feb 11;21(2):75-82.
Du HC, Simmons N, Faver JC, Yu Z, Palaniappan M, Riehle K, Matzuk MM. A Mild, DNA-Compatible Nitro Reduction Using B(2)(OH)(4). Org Lett. 2019 Apr 5;21(7):2194-2199. doi: 10.1021/acs.orglett.9b00497. Epub 2019 Mar 12. PubMed PMID: 30860855; PubMed Central PMCID: PMC6457042.
Li JY, Miklossy G, Modukuri RK, Bohren KM, Yu Z, Palaniappan M, Faver JC, Riehle K, Matzuk MM, Simmons N. Palladium-Catalyzed Hydroxycarbonylation of(Hetero)aryl Halides for DNA-Encoded Chemical Library Synthesis. Bioconjug Chem. 2019 Aug 21;30(8):2209-2215. doi: 10.1021/acs.bioconjchem.9b00447. Epub 2019 Jul 31
Teng X, Emmett MJ, Lazar MA, Goldberg E, Rabinowitz JD. Lactate Dehydrogenase C Produces S-2-Hydroxyglutarate in Mouse Testis. ACS Chem Biol. 2016 Sep 16;11(9):2420-7.
Odet F, Gabel S, London RE, Goldberg E, Eddy EM. Glycolysis and mitochondrial respiration in mouse LDHC-null sperm. Biol Reprod. 2013 Apr 18;88(4):95.
Faver JC, Riehle K, Lancia DR Jr, Milbank JBJ, Kollmann CS, Simmons N, Yu Z, Matzuk MM. Quantitative Comparison of Enrichment from DNA-Encoded Chemical Library Selections. ACS Comb Sci. 2019 Feb 11;21(2):75-82.
Du HC, Simmons N, Faver JC, Yu Z, Palaniappan M, Riehle K, Matzuk MM. A Mild, DNA-Compatible Nitro Reduction Using B(2)(OH)(4). Org Lett. 2019 Apr 5;21(7):2194-2199. doi: 10.1021/acs.orglett.9b00497. Epub 2019 Mar 12. PubMed PMID: 30860855; PubMed Central PMCID: PMC6457042.
Li JY, Miklossy G, Modukuri RK, Bohren KM, Yu Z, Palaniappan M, Faver JC, Riehle K, Matzuk MM, Simmons N. Palladium-Catalyzed Hydroxycarbonylation of(Hetero)aryl Halides for DNA-Encoded Chemical Library Synthesis. Bioconjug Chem. 2019 Aug 21;30(8):2209-2215. doi: 10.1021/acs.bioconjchem.9b00447. Epub 2019 Jul 31
