# Probes, Inhibitors, and PROTACs (PIP) Core

> **NIH NIH P20** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2024 · $152,311

## Abstract

Project Summary: Probes, Inhibitors, and PROTACs (PIP) Core
The overarching mission of the PIP Core is to use sophisticated chemistry and mass spectrometry for
development of small molecules that facilitate molecular target discovery and development. Genetic methods
are routinely used to identify, develop, and validate molecular targets. These methods rely on altering the DNA
or RNA sequences of the protein target. However, drug discovery relies on manipulating the function of the
corresponding proteins using small molecules. Often the results obtained through these complementary
strategies do not correlate.1 The incongruence associated with the results from these orthogonal approaches
can be attributed to the complex biology that is dependent on multiple functions i.e., enzymatic and scaffolding,
associated with the protein target. Modulating protein levels by altering the nucleic acids eliminates all the target
protein functions. However small molecule modulators can be tuned to induce either domain specific effects
(reversible or irreversible) or removal of the entire protein (PROTAC) with exquisite temporal control. These
could be tagged with photoactivatable or fluorescent molecules, or biotin to enable target identification and
validation, study mechanism of action, or characterize the associated interactome. In addition to the design and
synthesis of above types of small molecules, the PIP Core will also provide scale up services (mg to g) for
additional experiments such as in vivo validation of targets and hit-to-lead optimization studies to generate
structure activity relationship (SAR) data. Mass spectrometry will be used to characterize the impact of these
compounds on the proteome through quantitative analysis of proteins and posttranslational or chemical
modifications to validate mechanism of action and compensatory features that may contribute to drug resistance.
The Core will be led by Drs. Natarajan and Woods, who will bring complementary expertise to the PIP Core. Dr.
Natarajan has extensive expertise in developing probes, inhibitors, and PROTACs, using cutting edge chemistry
methods. Dr. Woods has extensive experience using mass spectrometry as a platform for delineating protein-
protein interactions, posttranslational modifications, and multivariate biomarkers of cancer response to therapy.
PIP Core services will be extensively utilized by CMTDD Research Project Leaders (RPLs), CMTDD members
and University researchers at large.

## Key facts

- **NIH application ID:** 10891534
- **Project number:** 5P20GM121316-07
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** Amarnath (Amar) Natarajan
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $152,311
- **Award type:** 5
- **Project period:** 2018-03-16 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10891534

## Citation

> US National Institutes of Health, RePORTER application 10891534, Probes, Inhibitors, and PROTACs (PIP) Core (5P20GM121316-07). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10891534. Licensed CC0.

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