# P7C3 based small molecule for Heart failure treatment

> **NIH NIH R61** · UNIVERSITY OF SOUTH FLORIDA · 2024 · $517,475

## Abstract

Summary
NAD+ is biosynthesized mainly through the salvage pathway and is central for cellular homeostasis and energy
production. Deficiency of NAD+ results in disruption of cellular functions, leading to decreased ability to
regenerate and repair. In heart failure (HF), the heart undergoes metabolic disruption leading to redox imbalance
with increased NADH/NAD+ ratio. Therefore, we hypothesized that “Activating NAD+ plays a central role in
attenuating Heart failure.” Current therapeutics manage the disease symptoms, however, do not address the
core issues of HF. Based on our innovation with US patents and new preliminary data, Nampt activator P7C3 is
a prototype for generation of new pharmacological class of small molecules for cardioprotection. Using medicinal
chemistry, 3D-SAR, cell permeability and drug design approaches we will activate NAD+ by P7C3-based novel
small molecules for attenuating HF. A combination and tiered approach will be utilized for evaluating and
narrowing down the new compound pipeline using in vitro models, followed with efficacy studies. Initial screening
through in vitro assay will identify the molecules that are of high affinity and activity. Subsequently, 8-9 new small
molecules will be tested using ex vivo Langendorff system for evaluating the cardiac changes, and NAD+
generation capacity. Finally, 1-2 lead small molecule(s) will be tested using in vivo system with preclinical model
of HF using isoproterenol infusion, alternate HF models include db/db and MI to evaluate the pharmacological
specificity by using a combination of cardiac-specific Nampt KO and wildtype (C57Bl/6J) mice for demonstrating
the increased function with NAD+ activation in HF. The milestone-based approach for R61 phase will be utilized
for medicinal chemistry, including design and synthesis of new small molecules, in vitro Nampt activity, cell
permeability and toxicity, and assessment of therapeutic candidate's ex vivo. Whereas, in the R33 phase, we
will perform pre-clinical assessment and pharmacological evaluation of 1-2 lead small molecule(s) in vivo. The
proposal provides a systematic plan for continuous assessment and refinement of project management to
develop P7C3-based small molecules for testing and refinement to achieve the milestones in a timely manner.
The University of South Florida is a top producer of patents and is highly supportive with cost matching during
R33 phase. In addition, the USF hosts incubator companies which along with pharmaceutical research
companies in Tampa Bay area have shown interest and support for this project. The PI is an expert and well
known in the region with pharmaceutical incubator companies and has received Florida High Tech Corridor
matching awards and therefore anticipate developing the lead compounds for commercialization through the
next stage of development. Overall, the successful completion of the project will allow new product development
with rigorous and robust evaluation along with project ...

## Key facts

- **NIH application ID:** 10891927
- **Project number:** 1R61HL170457-01A1
- **Recipient organization:** UNIVERSITY OF SOUTH FLORIDA
- **Principal Investigator:** Srinivas M. Tipparaju
- **Activity code:** R61 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $517,475
- **Award type:** 1
- **Project period:** 2024-09-05 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10891927

## Citation

> US National Institutes of Health, RePORTER application 10891927, P7C3 based small molecule for Heart failure treatment (1R61HL170457-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10891927. Licensed CC0.

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