# Developing chemical probes for oncogenic signaling pathways

> **NIH NIH R50** · H. LEE MOFFITT CANCER CTR & RES INST · 2023 · $293,933

## Abstract

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
th...

## Key facts

- **NIH application ID:** 10733845
- **Project number:** 2R50CA211447-06A1
- **Recipient organization:** H. LEE MOFFITT CANCER CTR & RES INST
- **Principal Investigator:** Harshani R Lawrence
- **Activity code:** R50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $293,933
- **Award type:** 2
- **Project period:** 2017-09-19 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10733845

## Citation

> US National Institutes of Health, RePORTER application 10733845, Developing chemical probes for oncogenic signaling pathways (2R50CA211447-06A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10733845. Licensed CC0.

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