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

Award Number: R01CA245739
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/14/2020
PERIOD OF PERFORMANCE END DATE: 06/30/2025

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


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $0 )
2026	2024	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Cancer Treatment Research	000	5	12/2/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $180,120 )
2024	2024	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Cancer Treatment Research	000	5	6/20/2024	NON-COMPETING CONTINUATION	$180,120
														Subtotal = $180,120

Issue Date FY: 2023 ( Subtotal = $185,808 )
2023	2023	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DRIVE	LA JOLLA	CA	92093	SAN DIEGO	USA	Cancer Treatment Research	000	4	6/28/2023	NON-COMPETING CONTINUATION	$185,808
														Subtotal = $185,808

Issue Date FY: 2022 ( Subtotal = $185,807 )
2022	2022	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Cancer Treatment Research	000	3	7/20/2022	NON-COMPETING CONTINUATION	$185,807
														Subtotal = $185,807

Issue Date FY: 2021 ( Subtotal = $189,600 )
2021	2021	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Cancer Treatment Research	000	2	6/22/2021	NON-COMPETING CONTINUATION	$189,600
														Subtotal = $189,600

Issue Date FY: 2020 ( Subtotal = $189,000 )
2020	2020	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Cancer Treatment Research	000	1	7/14/2020	NEW	$189,000
														Subtotal = $189,000

Grand Total All Awards = $930,335

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

Award Number: R01CA245739

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/14/2020

PERIOD OF PERFORMANCE END DATE: 06/30/2025

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