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Targeting chemoresistant prostate cancer with novel EED inhibitors

Award Number: R01CA256058
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2022
PERIOD OF PERFORMANCE END DATE: 03/31/2028

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Targeting chemoresistant prostate cancer with novel EED inhibitors - Docetaxel is the first-line chemotherapy for metastatic castration-resistant prostate cancer (PCa), the major cause of PCa mortality. Unfortunately, in most cases PCa develops docetaxel resistance and continues to progress, which has no cure. Our recent studies (Theranostics, 2021, May 8; 11: 6873-6890) have provided strong evidence demonstrating that chemoresistant PCa cells rely on an active EED-EZH2-Stat3-SKP2- ABCB1/survivin signaling to survive and evade standard chemotherapy. In this R01 project, we hypothesize that targeting EED-EZH2 interaction with novel EED inhibitors is effective to overcome chemoresistance and eliminate lethal PCa cells. In Aim 1, we will conduct rational design and chemical optimization of novel EED inhibitors. A total of 200 new chemical entities will be designed and synthesized. In Aim 2, We will validate the mechanism of action of potential leads in chemoresistant PCa cells. We will identify the in vitro and in vivo activities of new EED inhibitors against chemoresistant PCa in multiple, heterogenous preclinical models of chemoresistant PCa. In Aim 3, we will conduct Good Laboratory Practice (GLP) and non-GLP studies to evaluate the drug-like properties of lead compounds, including pharmacokinetics, absorption, distribution, metabolism, and excretion (ADME), single- and repeat-dose toxicity and safety pharmacology. With successful accomplishment of this project, we expect to identify 1~2 patentable lead compounds and advance them into further preclinical and clinical development. The overarching goal is to translate our basic research into an effective and safe treatment for lethal PCa, therefore benefiting patients and improving clinical outcomes.


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: 2025 ( Subtotal = $428,304 )
2025	2025	CLARK ATLANTA UNIVERSITY, INC.	223 JAMES P BRAWLEY DR SW	ATLANTA	GA	30314	FULTON	USA	Cancer Treatment Research	000	4	4/30/2025	NON-COMPETING CONTINUATION	$385,474
2025	2025	CLARK ATLANTA UNIVERSITY, INC.	223 JAMES P BRAWLEY DR SW	ATLANTA	GA	30314	FULTON	USA	Cancer Treatment Research	001	4	5/23/2025	NON-COMPETING CONTINUATION	$42,830
														Subtotal = $428,304

Issue Date FY: 2024 ( Subtotal = $161,169 )
2024	2024	CLARK ATLANTA UNIVERSITY, INC.	223 JAMES P BRAWLEY DR SW	ATLANTA	GA	30314	FULTON	USA	Cancer Treatment Research	001	3	9/12/2024	SUPPLEMENT FOR EXPANSION	$56,208
2024	2024	CLARK ATLANTA UNIVERSITY, INC.	223 JAMES P BRAWLEY DR SW	ATLANTA	GA	30314	FULTON	USA	Cancer Treatment Research	000	3	9/11/2024	NON-COMPETING CONTINUATION	$104,961
														Subtotal = $161,169

Issue Date FY: 2023 ( Subtotal = $522,596 )
2023	2023	CLARK ATLANTA UNIVERSITY, INC.	223 JAMES P BRAWLEY DR SW	ATLANTA	GA	30314	FULTON	USA	Cancer Treatment Research	000	2	4/24/2023	NON-COMPETING CONTINUATION	$463,429
2023	2023	CLARK ATLANTA UNIVERSITY, INC.	223 JAMES P BRAWLEY DR SW	ATLANTA	GA	30314	FULTON	USA	Cancer Treatment Research	001	2	5/12/2023	SUPPLEMENT FOR EXPANSION	$59,167
														Subtotal = $522,596

Issue Date FY: 2022 ( Subtotal = $543,181 )
2022	2022	CLARK ATLANTA UNIVERSITY, INC.	223 JAMES P BRAWLEY DR SW	ATLANTA	GA	30314	FULTON	USA	Cancer Treatment Research	000	1	3/11/2022	NEW	$543,181
														Subtotal = $543,181

Grand Total All Awards = $1,655,250

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Targeting chemoresistant prostate cancer with novel EED inhibitors

Award Number: R01CA256058

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/01/2022

PERIOD OF PERFORMANCE END DATE: 03/31/2028

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