Development of small molecule inhibitors of RBM46 as novel male contraceptives
NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development
About This Grant
PROJECT SUMMARY/ABSTRACT Development of novel contraceptive strategies is central to the mission of the Contraceptive Research Branch of the NICHD. This goal is driven by a global need for effective contraceptive methods to address: 1) the glut of unintended pregnancies (~45% of US pregnancies in 2011); 2) the high rate of elective abortion (1.15M unintended pregnancies ended in abortion in 2011 in the US); and 3) the high risk of maternal mortality (~830 women/day worldwide die due to pregnancy or childbirth complications). In a search for novel male contraceptive drug targets, we identified RBM46, which is a germ cell-specific RNA binding protein expressed by germ cells on the basement membrane of seminiferous tubules (outside the blood-testis-barrier), and is essential for spermatogenesis. Indeed, Rbm46 knockout mice are sterile and have no other phenotype, raising the distinct possibility that targeting RBM46 could lead to safe and effective male contraception by blocking spermatogenesis at the differentiating spermatogonial stage. Thus, we propose to develop drugs that target degradation of RBM46 as a means of oral, non-hormonal male contraception, which will significantly advance additional safe and reversible options for male contraception towards the clinic. Specifically, we will combine: 1) exceptional expertise in drug screening and development at UTSA and UT Health San Antonio; 2) leading expertise in male reproduction, spermatogenesis, and infertility at UTSA and ECU; 3) close proximity to one of two NIH-designated Marmoset Breeding Colonies, maintained at the Southwest National Primate Research Center; 4) growing and ongoing experience collecting and assessing marmoset sperm; 5) published experience in the use of cutting- edge single-cell genomics to assess normality of spermatogenic cell types; and 6) documented expertise with spermatogonial stem cell (SSC) transplantation. In Aim 1, we will identify small molecules that bind RBM46 and could be used to develop PROTACs. In Aim 2, we will produce initial RBM46 PROTACs and validate that they degrade the protein in vitro. In Aim 3, we will use medicinal chemistry to optimize the drug-like characteristics of top validated RBM46 PROTACs. In Aims 4 and 5, we will determine whether optimized RBM46 PROTACs induce reversible contraception in vivo using mice and marmosets, respectively. Together, these Aims are designed to advance RBM46 degradation as a novel strategy to achieve reversible, non-hormonal male contraception and provide key results to justify further preclinical investigation and eventual commercialization.
Grant Summary
Development of small molecule inhibitors of RBM46 as novel male contraceptives is a NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development grant providing up to $745K for university, nonprofit, healthcare org. Applications are due 2029-01-31 (open). Check eligibility and apply with FindGrants.
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How to Apply
Up to $745K
2029-01-31
- 1Confirm your organization is eligible for Development of small molecule inhibitors of RBM46 as novel male contraceptives from NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development before the deadline.
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Development of small molecule inhibitors of RBM46 as novel male contraceptives: Frequently Asked Questions
Who is eligible for the Development of small molecule inhibitors of RBM46 as novel male contraceptives?
Development of small molecule inhibitors of RBM46 as novel male contraceptives is offered by NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the Development of small molecule inhibitors of RBM46 as novel male contraceptives provide?
Development of small molecule inhibitors of RBM46 as novel male contraceptives provides up to $745K per award from NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the Development of small molecule inhibitors of RBM46 as novel male contraceptives deadline?
Applications for Development of small molecule inhibitors of RBM46 as novel male contraceptives are due 2029-01-31 (open). Because deadlines can change, verify the date with the funder, NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Development of small molecule inhibitors of RBM46 as novel male contraceptives?
To apply for Development of small molecule inhibitors of RBM46 as novel male contraceptives, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development.