Wednesday, December 3, 2025 12/3/2025

Development of non-ATP competitive chemical biology probes to elucidate mechanisms of PLK1 activation and stability.

Award Number: R21CA263359
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2021
PERIOD OF PERFORMANCE END DATE: 06/30/2025

Group Awards By:

View Award Description

Development of non-ATP competitive chemical biology probes to elucidate mechanisms of PLK1 activation and stability. - Polo-like kinase 1 (PLK1) is a central player in regulating entry into and progression through mitosis. Many studies have validated PLK1 as an anti-tumor drug target, and its inhibition is potently anti-proliferative to cancer cells. We have discovered a series of compounds that bind potently to the polo-box domain of PLK1 named abbapolins through a cryptic pocket and which induce proteasome mediated degradation of the PLK1 protein in a dose dependent manner without the addition of a ligand to recruit an E3 ligase to promote ubiquitination (PROTAC approach). The abbapolins are also able to inhibit the phosphorylation of a PLK1 specific marker while potently inhibiting the proliferation of prostate cancer cell lines. As a result of these exciting observations, we propose to further develop these inhibitors as potent PBD inhibitors and degraders of PLK1 while using them as chemical biology probes to provide new insights the regulation of PLK1 activity through conformational change, substrate recognition and proteasomal stability. Our experiments will therefore shed new light into the regulation of PLK1 at the cellular level while generating novel data on the molecular determinants and features important for inhibition. In turn this may provide understanding of the factors contributing to the lack of clinical activity for the ATP competitive inhibitors of the PLK mitotic kinases while laying the groundwork for preclinical and clinical development the abbapolins as cancer therapeutics with a unique mechanism of action.


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	2022	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST	COLUMBIA	SC	29208	RICHLAND	USA	Cancer Treatment Research	000	2	11/21/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST	COLUMBIA	SC	29208	RICHLAND	USA	Cancer Treatment Research	000	2	7/19/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $170,662 )
2022	2022	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST # 414	COLUMBIA	SC	29208	RICHLAND	USA	Cancer Treatment Research	000	2	8/11/2022	NON-COMPETING CONTINUATION	$170,662
														Subtotal = $170,662

Issue Date FY: 2021 ( Subtotal = $208,973 )
2021	2021	UNIVERSITY OF SOUTH CAROLINA	1600 HAMPTON ST # 414	COLUMBIA	SC	29208	RICHLAND	USA	Cancer Treatment Research	000	1	6/24/2021	NEW	$208,973
														Subtotal = $208,973

Grand Total All Awards = $379,635

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Development of non-ATP competitive chemical biology probes to elucidate mechanisms of PLK1 activation and stability.

Award Number: R21CA263359

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/2021

PERIOD OF PERFORMANCE END DATE: 06/30/2025

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer