Wednesday, January 28, 2026 1/28/2026

Expanding the targetable landscape in cancer with serine-targeting covalent ligands

Award Number: R21CA280163
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/16/2024
PERIOD OF PERFORMANCE END DATE: 01/31/2027

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Expanding the targetable landscape in cancer with serine-targeting covalent ligands - Project Summary Targeted covalent inhibitors have empowered the potent and selective targeting of driver oncogenes in cancer. Between 2011 and 2021, 16 new covalent drugs (12 with cancer indications) were approved by the US FDA, with the recent notable example of the first KRAS inhibitor sotorasib. However, most of current covalent drug discovery efforts are directed toward cysteines, which is the least abundant amino acid in the proteome (2%). Meanwhile, about 6% of mutants in cancer lead to serines. While some of these mutations directly contribute to oncogenic signaling (e.g. KRAS G12S), others confer clinical resistance to existing drugs (e.g. EGFR C797S, BTK C481S). To date, direct engagement of these mutant serines have not be achieved. Methods to selectively engage amino acids beyond cysteine are highly desirable, as they will bridge the gap between the prevalence of serine-acquiring mutations in human cancer and the lack of chemical tools to target them. This project aims to develop new chemistry that enables the covalent engagement of serine residues, especially those acquired in cancer such as EGFR(C797S) (Aim 1) and BTK C481S (Aim 2). Successful targeting of these proteins will provide new avenues for targeted cancer therapy. The chemistry developed in this project will also serve as a platform for the discovery of new covalent ligands for currently “undruggable” cancer targets (Aim 3).


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	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Cancer Treatment Research	000	2	12/3/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $187,584 )
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Cancer Treatment Research	001	2	5/29/2025	NON-COMPETING CONTINUATION	$18,757
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Cancer Treatment Research	000	2	3/5/2025	NON-COMPETING CONTINUATION	$168,827
														Subtotal = $187,584

Issue Date FY: 2024 ( Subtotal = $225,101 )
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Cancer Treatment Research	000	1	2/16/2024	NEW	$225,101
														Subtotal = $225,101

Grand Total All Awards = $412,685

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Expanding the targetable landscape in cancer with serine-targeting covalent ligands

Award Number: R21CA280163

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/16/2024

PERIOD OF PERFORMANCE END DATE: 01/31/2027

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