# A2B receptor stimulation for sepsis

> **NIH NIH R41** · PURINE PHARMACEUTICALS, INC. · 2022 · $226,287

## Abstract

SUMMARY
 Sepsis is a medical condition caused by an overwhelming systemic inflammatory response to infection.
Although the underlying infection can now be efficiently treated with antibiotics, there are no effective therapies
to control the organ damage caused by the inflammatory response of the host. As a result, sepsis is the leading
cause of mortality in intensive care units and is the tenth leading cause of death overall in the US. Extracellular
adenosine is a biologically active signaling molecule that accumulates at sites of metabolic stress in sepsis.
Extracellular adenosine has potent anti-inflammatory effects by binding to and activating G protein-coupled A2B
adenosine receptors (ARs) on the surface of immune and endothelial cells. Using A2BAR deficient mice and
pharmacological antagonists, we have discovered that A2BARs protect mice against polymicrobial sepsis-induced
inflammation, organ damage, and mortality. Based on these results, we hypothesize that pharmacological
stimulation of A2BARs protects against septic mortality and organ injury by suppressing inflammation. To address
this hypothesis, we will study the efficacy of two novel, potent and selective A2BAR agonists we developed, P453
and P517, in reversing septic mortality, inflammation, and organ dysfunction. The Specific Aims of the proposal
are: Specific Aim 1. Assess the effect of P453 and P517 on mortality in murine sepsis. Specific Aim 2. Delineate
the effect of P453 and P517 on inflammation and organ injury in murine sepsis. This proposal thus advances
new therapeutic applications to control and/or alleviate sepsis-induced organ injury and mortality.

## Key facts

- **NIH application ID:** 10545455
- **Project number:** 1R41AI170049-01A1
- **Recipient organization:** PURINE PHARMACEUTICALS, INC.
- **Principal Investigator:** George HASKO
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $226,287
- **Award type:** 1
- **Project period:** 2022-07-15 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10545455

## Citation

> US National Institutes of Health, RePORTER application 10545455, A2B receptor stimulation for sepsis (1R41AI170049-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10545455. Licensed CC0.

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