# Discovery of PD-1/PDL-1 inhibitors from marine microbial natural products

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $189,600

## Abstract

Project Summary and Relevance
Project Summary:
The broad, long-term objective of this collaborative project is the discovery of small molecule
therapeutics that can replace antibodies as inhibitors of the PD-1 checkpoint. To date, no small
molecules have been approved for this application, although the benefits of small molecules
over biologicals in drug therapy is clear. This project capitalizes on the existence of a large
collection (up to 30,000 samples) of structurally unique marine microbial metabolites that have
shown to be a solid source for the development of anticancer agents. This collection, available
at the Scripps Institution of Oceanography, UCSD, from Dr. William Fenical will be interfaced
with the cancer biology lab of Dr. Yin Lu at the Nanjing University of Chinese Medicine, to
screen for selective inhibitors using a commercially-available cell-based bioassay for PD-1
binding. When active metabolites are discovered, they will be screened in a variety of secondary
assays to show selective binding. Finally, verified PD-1binding inhibitors will be produced in
multi-milligram amounts by large-scale cultivation and provided to Dr. Lu for evaluation in
mouse and rat xenograph models of select cancers.
Relevance:
This project aims to improve on the immunotherapy of cancer by discovering small molecules
that selectively bind to the protein PD-1, which when bound to PDL-1 is responsible for the
deactivation of the immune system. Replacing the current antibody (protein) therapy with a
small molecule drug is likely to improve treatment efficacy and will clearly reduce drug cost.

## Key facts

- **NIH application ID:** 10216205
- **Project number:** 5R01CA245739-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** William Fenical
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $189,600
- **Award type:** 5
- **Project period:** 2020-07-14 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10216205

## Citation

> US National Institutes of Health, RePORTER application 10216205, Discovery of PD-1/PDL-1 inhibitors from marine microbial natural products (5R01CA245739-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10216205. Licensed CC0.

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