# DEL Screening Campaign for Contraceptive and Cancer Targets

> **NIH NIH R21** · UNIVERSITY OF MINNESOTA · 2024 · $232,500

## Abstract

Project summary/abstract.
The emerging field of allosteric inhibition of protein kinases has the potential to provide highly
targeted therapeutics for diverse diseases without undesirable side effects. Our long-term goal is
the discovery and development of highly selective allosteric inhibitors for side effect-free cancer
chemotherapy and for reversible non-hormonal contraception. The overall objective of this
application is to identify novel allosteric inhibitors for four kinases: WEE1-like protein kinase 2
(WEE2), testis-specific serine/threonine kinase 1 (TSSK1), cyclin-depended kinase 11 (CDK11),
and cyclin dependent kinase 2 (CDK2) by screening DNA encoded libraries (DEL) consisting of
2B compounds. The four kinases are validated drug targets: WEE2 for female non-hormonal
contraception, TSSK1 for male non-hormonal contraception, CDK11 for cancer chemotherapy
and CDK2 for cancer and male and female non-hormonal contraception. WEE2, TSSK1 and
CDK11 are on the NIH list of underexplored targets. CDK2 inhibitors have been studied for cancer
application but limited studies have been carried out for male contraception and none for female
contraception. Hit compounds from the DEL screen will be resynthesized by conventional
synthesis and then confirmed by using functional biochemical assays, orthogonal confirmatory
assays, and biochemical and biophysical assays to determine allosteric binding. Validated
compounds will be tested in a 24 kinome screen for kinase selectivity and in a limited set of in
vitro ADMET assays to assess their drug-like properties. CDK11 and CDK2 inhibitors will be
tested in cancer cell lines that express their respective targets. TSSK1 inhibitors will be tested
using a computer-assisted sperm analyzer (CASA) for sperm motility measurements. Selective
allosteric inhibitors identified in this project are expected to be useful probes to investigate the
biology of the four kinases and to serve as early leads for drug discovery.

## Key facts

- **NIH application ID:** 10870842
- **Project number:** 1R21HD115181-01
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Gunda I. Georg
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $232,500
- **Award type:** 1
- **Project period:** 2024-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10870842

## Citation

> US National Institutes of Health, RePORTER application 10870842, DEL Screening Campaign for Contraceptive and Cancer Targets (1R21HD115181-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10870842. Licensed CC0.

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