# Targeting BRDT (testis-specific bromodomain) for Male Contraception

> **NIH NIH P50** · UNIVERSITY OF MINNESOTA · 2020 · $230,666

## Abstract

PROJECT SUMMARY
A pharmacologic approach for male contraception remains a longstanding challenge in medicine. Recent
research from our laboratories has shown that the small-molecule inhibitor JQ1 of the bromodomain and
extraterminal (BET) subfamily of epigenetic reader proteins is a potent inhibitor of BRDT and that the observed
contraceptive effect of JQ1 is completely reversible. However, JQ1 is a pan-BET inhibitor and therefore selective
BRDT inhibitors are needed that can act as safe, effective, and reversible non-hormonal male contraceptive
therapeutic agents. We thus propose research directed at the discovery, optimization, biochemical
characterization, mechanistic understanding, in vivo evaluation of contraceptive effect reversibility, and clinical
translation of BRDT inhibitors. In Specific Aim 1, we propose four chemical platforms to discover BRDT-selective
bromodomain inhibitors for male contraception: 1) novel non-obvious mimetics of acetyl-lysine; 2) inhibitors that
specifically target a unique residue in human BRDT; 3) unique ligands that can bind selectivly to both
bromodomains of BRDT; and 4) bifunctional small molecules designed to direct selective degradation of the
BRDT protein. Structure-based drug design, biochemical, and biophysical studies will be used to drive selectivity
improvements. For Specific Aim 2, the selective BDRT inhibitors identified from Specific Aim 1 will be further
optimized for cellular potency and selectivity for BRDT through an iterative process that will also involve in vitro
testing for ADMET properties. Specific Aim 3 will explore the clinical potential of the inhibitors through in vivo
pharmacokinetic studies and pre-clinical evaluation for male contraception, involving definitive studies of
spermatogenesis, fertility, and reversibility in male mice.

## Key facts

- **NIH application ID:** 9931062
- **Project number:** 5P50HD093540-04
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Jun QI
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $230,666
- **Award type:** 5
- **Project period:** — → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9931062

## Citation

> US National Institutes of Health, RePORTER application 9931062, Targeting BRDT (testis-specific bromodomain) for Male Contraception (5P50HD093540-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9931062. Licensed CC0.

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