Development of TPST Inhibitors as Non-Hormonal Male Contraceptives

DESCRIPTION (provided by applicant): The development of safe and effective female oral contraceptives (OCs) in the early 1960s provided a superior means of contraception and forever changed the dynamics of family planning. In fact, 82% of all women in the U.S. have used OCs, which are one of the most widely prescribed drugs in the U.S. Although contraceptive research has provided a range of choices for women, no male contraceptive drug is currently available. Currently vasectomy and condoms are the only con traceptive options available for men. Scientists at Siwa Biotech Corporation have identified tyrosylprotein sulfotransferase-2 (TPST-2) as a novel target enzyme for the development a male contraceptive. Using a TPST-2 knockout mouse model, we have demonstr ated that male mice that lack the TPST-2 enzyme are infertile, whereas TPST-1 deficient mice have normal fertility. TPST-2 deficient males have normal sexual behavior and copulate at rates similar to normal mice. Testosterone levels are normal, testis hist ology is normal, and sperm counts and sperm morphology are normal. Most importantly, TPST-2 deficient mice appear to be otherwise unaffected by the lack of TPST-2 with respect to observable health or behavioral issues. These data suggest that a selective T PST-2 inhibitor is a strong candidate for development of a reversible, non-hormonal male contraceptive. Successful development of a safe and effective male oral contraceptive would be a major advance. A male oral contraceptive would be a first-in-class dru g that could capture a large untapped market and would likely be a popular choice for both men and their partners. The goal of this SBIR Phase I grant application is to develop, optimize and validate a high-throughput screening platform as a first step to identify novel small molecules that inhibit TPST-2 activity with therapeutic potential as a male contraceptive. Project Narrative: The project described in this application is eligible and most suited for this SBIR Phase I award because; 1) the pro ject seeks to develop a novel, non-hormonal male contraceptive, 2) there are no FDA-approved oral male contraceptives and this is a large market currently not serviced by any remedy, 3) the applicant company, Siwa Biotech Corp., is a small business in the State of Oklahoma, and the award will initiate the development of a therapeutic product that requires clinical evaluation and FDA approval, 4) the award will allow the identification of lead compounds and provide needed funding to bring this product to the commercial market in a timely fashion; and 5) the product being developed has the potential to contribute considerably to the economy of the State of Oklahoma and the nation, as well as to the enhancement of public health.