# Young, Lindon H

> **NIH NIH R43** · YOUNG THERAPEUTICS, LLC · 2021 · $560,261

## Abstract

PROJECT SUMMARY
We are seeking funding to test the cardio protective effects of a novel new protein kinase C epsilon (PKCε)
inhibitor (YT-002) and a novel protein kinase C beta II (PKCβII) inhibitor (YT-004) in the setting of porcine
myocardial ischemia reperfusion (I/R) in vivo when given at the beginning of reperfusion. There currently is no
approved pharmacological treatment/preventative for the I/R injury. We are fully aware of the past failures in this
area. Literally all previous attempts have taken the oxygen free radical scavenging approach. We believe this
underlies, at least in part, the reason there have been no successful pharmacological therapeutics for cardiac
I/R injury to date. Once reactive oxygen species are generated the damage is immediate and scavenging is
ineffective. Our approach – never been tried before – is to inhibit the generation of reactive oxygen species thus
preventing their damage during reperfusion. Interviews we conducted with 22 interventional cardiologists
overwhelmingly support the idea that such preservation of myocardial tissue and function would represent a
significant long-term benefit to the patients experiencing ischemia-reperfusion injury leading to a decrease in the
incidence of heart failure. Previous data from our lab with another compound YT-001 (identical mechanism of
action as YT-002) demonstrated a significant inhibition of hydrogen peroxide generation in vivo, and a
remarkable sparing of tissue damage and cardiac function post reperfusion in both the ex vivo rat I/R heart and
the in vivo porcine myocardial I/R model. However, YT-001 has limited solubility and remaining patent life. Our
new molecules (YT-002 and YT-004) have dramatically improved solubility, potency and new patent life. We
have already demonstrated impressive infarct size reduction and cardiac function protection in isolated rat I/R
hearts with YT-002 and YT-004. In this proposal, we will evaluate the cardio protective effects of YT-002 and
YT-004 on ischemia reperfusion in the Gorman pig model (19). In addition to the animal’s vital signs, ejection
fraction (measured by echocardiography) will be monitored (as an index of cardiac function/contractility) as well
as cardiac proteins (e.g., troponin I) as an index of tissue damage throughout the protocol. Three hours after
reperfusion, the hearts will be excised, and stained for direct assessment of cardiac damage (infarct size).
Immunohistochemistry on frozen heart sections will be performed in Dr. Young’s lab at PCOM to detect PKCε
and PKCβII localization. Based upon previously generated pig heart data with the PKCε inhibitor YT-001, we
expect to see a dramatic in vivo preservation of cardiac tissue and function compared to animals receiving
scrambled peptide control. These positive data will provide additional justification for performing longer-term
animal efficacy studies and eventually Investigational New Drug (IND) enabling studies in support of human
clinical trials.

## Key facts

- **NIH application ID:** 10324843
- **Project number:** 1R43HL160338-01
- **Recipient organization:** YOUNG THERAPEUTICS, LLC
- **Principal Investigator:** Lindon H Young
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $560,261
- **Award type:** 1
- **Project period:** 2021-08-10 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10324843

## Citation

> US National Institutes of Health, RePORTER application 10324843, Young, Lindon H (1R43HL160338-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10324843. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*