# Optimization of lead candidates for an on-demand male contraceptive

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2024 · $682,405

## Abstract

Mammalian sperm are stored in the epididymis in a dormant state; they are immotile and unable
to fertilize the egg. Upon ejaculation, sperm begin swimming and initiate a process called
capacitation, where they become competent to fertilize. An initial event in capacitation and
activation of motility is the HCO3- induced stimulation of soluble adenylyl cyclase (sAC: ADCY10).
Men and male mice with the sAC gene knocked out are infertile, and pharmacological inhibitors
specific for sAC block in vitro fertilization and temporarily render male mice infertile. Thus, sAC is
a genetic and pharmacologically validated, non-hormonal target essential for male fertility. The
overall hypothesis tested in this application is that sAC inhibitors can be designed which can be
appropriately dosed to block sperm functions while minimizing undesirable side effects. We
propose to test a series of potent, selective sAC inhibitors, using in vitro and in vivo studies of
efficacy, safety, and pharmacokinetics, to identify the most well-developed, potent, selective,
drug-like, non-toxic sAC inhibitors. The goal of this Project is to advance a compound from this
series into preclinical development candidates suitable for development partners to apply for an
FDA Investigational New Drug (IND) for a novel oral, non-hormonal contraceptive.

## Key facts

- **NIH application ID:** 10933039
- **Project number:** 5R01HD111549-02
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** JOCHEN BUCK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $682,405
- **Award type:** 5
- **Project period:** 2023-09-21 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10933039

## Citation

> US National Institutes of Health, RePORTER application 10933039, Optimization of lead candidates for an on-demand male contraceptive (5R01HD111549-02). Retrieved via AI Analytics 2026-08-12 from https://api.ai-analytics.org/grant/nih/10933039. Licensed CC0.

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