# Optimization and pre-clinical evaluation of ADCY10 inhibitors

> **NIH NIH P50** · WEILL MEDICAL COLL OF CORNELL UNIV · 2021 · $714,873

## Abstract

Project 1
Freshly ejaculated mammalian sperm are unable to fertilize an egg. They acquire fertilizing
capacity in the hours following ejaculation, as they pass through the female reproductive tract, in
a process known as capacitation. Soluble adenylyl cyclase (sAC: ADCY10) is a non-hormonal
target essential for sperm capacitation and male fertility. Pharmacological sAC inhibitors block
sperm functions in vitro and two distinct sAC knockout (KO) mouse strains exhibit male-specific
sterility without exhibiting other overt phenotypes. The overall hypothesis tested in this
Contraception Research Center (CRC) is that sAC inhibitors can be designed which can be
appropriately dosed to block sperm functions while minimizing undesirable side effects. In this
Contraception Development Research Project, we will perform additional medicinal chemistry
optimization of a series of potent, selective sAC inhibitors, along with in vivo studies of efficacy,
safety, and pharmacokinetics, to ultimately produce 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:** 10144840
- **Project number:** 5P50HD100549-03
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** LONNY R LEVIN
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $714,873
- **Award type:** 5
- **Project period:** 2019-09-12 → 2022-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10144840

## Citation

> US National Institutes of Health, RePORTER application 10144840, Optimization and pre-clinical evaluation of ADCY10 inhibitors (5P50HD100549-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10144840. Licensed CC0.

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