Wednesday, September 17, 2025 9/17/2025

Developing chemical probes for oncogenic signaling pathways

Award Number: R50CA211447
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/19/2017
PERIOD OF PERFORMANCE END DATE: 08/31/2028

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Developing chemical probes for oncogenic signaling pathways - Abstract: The goal of the NCI Research Specialist Award prepared by Dr. Harshani Lawrence “Developing chemical probes for oncogenic signaling pathways” will promote identification of small molecules/chemical probes for cancer targets to elucidate underlying molecular mechanisms driving cancer and drug discovery research at the Moffitt Cancer Center (Moffitt). Dr. Lawrence, a synthetic/medicinal chemist with over 20 years of cancer research experience, is the Scientific and Managing Director of the Chemical Biology Core (CBC) at Moffitt. Dr. John Cleveland, Center Director of the Moffitt NCI-designated Comprehensive Cancer Center and PI/PD of the Cancer Center Support Grant (CCSG) P30 CA076292 will serve as the Unit Director for this R50 NCI Research Specialist Award and provide leadership, guidance and be responsible for executive oversight and resource allocation to the CBC. The 4 projects described in this proposal will involve synthesis of drug-like compounds that are inhibitors of the 1. ACK1 and 2. ULK3 serine/threonine kinases, 3. Development of bifunctional gilteritinib degraders, and 4. Validation of novel inhibitors of PERK. The synthetic chemistry strategies/approaches described in this proposal will generate novel compounds to address significant challenges in several types of human cancers. Evaluation of novel, potent and selective inhibitors of ACK1 to target PTPN11-mutant cancers that harbor SHP2 (PTPN11) mutations and breast cancer will generate novel compounds for advanced pre-clinical studies. Potent and selective ULK3 inhibitors will lead to our understanding of drug resistance in Multiple myeloma and novel strategies for treatment of the disease. The synthesis and validation of bifunctional molecules as PROTACs for gilteritinib is expected to advance the field/help to define tractable targets for leukemia. Synthesis/validation of novel potent inhibitors of protein ER kinase (PKR)-like ER kinase (PERK) to reduce tumor promoted immune evasion and thereby reduce tumor growth. As part of this award, Dr. Lawrence will continue to provide the Moffitt research community with critical enabling chemical biology support. This will include structure based design and synthesis of focused libraries (hit-to-lead-optimization) to identify new compounds/chemical probes to explore the molecular mechanisms of proteins involved in cancer; scale-up synthesis/formulation of potent compounds (e.g. prodrug/salt formation, solvent/excipient optimization) for in-vivo studies; design/synthesis of chemical probes for affinity-based proteomics. In addition to the projects described here, she is involved in several other medicinal chemistry collaborations with Cancer Center members, and she is in a unique position to integrate projects from the Molecular Medicine and Immunology programs. Dr. Lawrence’s contribution via synthesis of compounds is essential for peer reviewed publications and grant applications. The research projects/strategies described in this application will facilitate new directions, approaches, chemical probes /drugs to study and target cancer.


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 = $293,933 )
2025	2025	H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE HOSPITAL, INC.	12902 USF MAGNOLIA DR	TAMPA	FL	33612	HILLSBOROUGH	USA	Cancer Treatment Research	000	8	8/19/2025	NON-COMPETING CONTINUATION	$293,933
														Subtotal = $293,933

Issue Date FY: 2024 ( Subtotal = $293,933 )
2024	2024	H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE HOSPITAL, INC.	12902 USF MAGNOLIA DR	TAMPA	FL	33612	HILLSBOROUGH	USA	Cancer Treatment Research	000	7	8/8/2024	NON-COMPETING CONTINUATION	$293,933
														Subtotal = $293,933

Issue Date FY: 2023 ( Subtotal = $293,933 )
2023	2023	H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE HOSPITAL, INC.	12902 MAGNOLIA DR	TAMPA	FL	33612	HILLSBOROUGH	USA	Cancer Treatment Research	001	6	9/19/2023	COMPETING CONTINUATION	$293,933
2023	2021	H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE HOSPITAL, INC.	12902 MAGNOLIA DR	TAMPA	FL	33612	HILLSBOROUGH	USA	Cancer Treatment Research	000	5	6/22/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $293,933

Issue Date FY: 2021 ( Subtotal = $197,614 )
2021	2021	H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE HOSPITAL, INC.	12902 MAGNOLIA DR	TAMPA	FL	33612	HILLSBOROUGH	USA	Cancer Treatment Research	000	5	8/30/2021	NON-COMPETING CONTINUATION	$197,614
														Subtotal = $197,614

Issue Date FY: 2020 ( Subtotal = $197,614 )
2020	2020	H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE HOSPITAL, INC.	12902 MAGNOLIA DR	TAMPA	FL	33612	HILLSBOROUGH	USA	Cancer Treatment Research	000	4	8/25/2020	NON-COMPETING CONTINUATION	$197,614
														Subtotal = $197,614

Issue Date FY: 2019 ( Subtotal = $197,614 )
2019	2019	H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE HOSPITAL, INC.	12902 MAGNOLIA DR	TAMPA	FL	33612	HILLSBOROUGH	USA	Cancer Treatment Research	000	3	8/15/2019	NON-COMPETING CONTINUATION	$197,614
														Subtotal = $197,614

Issue Date FY: 2018 ( Subtotal = $197,614 )
2018	2018	H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE HOSPITAL, INC.	12902 MAGNOLIA DR	TAMPA	FL	33612	HILLSBOROUGH	USA	Cancer Treatment Research	000	2	8/23/2018	NON-COMPETING CONTINUATION	$197,614
														Subtotal = $197,614

Issue Date FY: 2017 ( Subtotal = $197,614 )
2017	2017	H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE HOSPITAL, INC.	12902 MAGNOLIA DR	TAMPA	FL	33612	HILLSBOROUGH	USA	Cancer Treatment Research	000	1	9/21/2017	NEW	$197,614
														Subtotal = $197,614

Grand Total All Awards = $1,869,869

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Developing chemical probes for oncogenic signaling pathways

Award Number: R50CA211447

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/19/2017

PERIOD OF PERFORMANCE END DATE: 08/31/2028

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