Small molecule FPR/NOX2 agonists
Development of proprietary unique nM potent agonist of FPR/NOX2
for treatment of autoimmunity, inflammation and infections
Developing small molecule FPR-NOX2 agonist
ProNoxis develops products for the treatment of autoimmune, inflammatory and infectious diseases characterized by a large unmet medical need and either large patient populations or high-value niche therapy areas.
In developing NOX2-activating drugs, ProNoxis aims at a totally new mechanism for inhibiting and treating inflammation and infections.
NOX2-produced ROS is an important and effective natural mechanism for the immune system to control the inflammatory and autoimmune responses.
ProNoxis has identified small-molecule compounds for selective and efficient activation of the Formyl- peptide receptor-1 (FPR1) to activate NOX2. Proof of concept experiments using in vitro systems as well as relevant in vivo models shows disease amelioration effects.
For later-stage preclinical development and progress towards clinical development for relevant indications, Pronoxis is open for joint ventures and collaborations to apply Pronoxis proprietary compounds for further development.
Selective FPR1 agonist
Dual pro-inflammatory and pro-resolving effects of FPR2/ALX signalling. Endogenous FPR2/ALX lipid and protein ligands exert both pro-inflammatory.
Monika Maciuszek et al. European Journal of Medicinal Chemistry
Volume 213, 5 March 2021, 113167 - Under a Creative Commons license
FPR2/ALX Receptor and its therapeutic areas.
Monika Maciuszek et al. European Journal of Medicinal Chemistry
Volume 213, 5 March 2021, 113167 - Under a Creative Commons license
Publications
Pronoxis lead compound RE-04-001 has been shown to specifically target and activate FPR1, with an EC50 ∼1 nM)
Lind, S, Dahlgren, C, Holmdahl, R, Olofsson, P, Forsman, H. Functional selective FPR1 signalling in favour of an activation of the neutrophil superoxide generating NOX2 complex. J Leukoc Biol. 2021; 109: 1105– 1120. https://doi.org/10.1002/JLB.2HI0520-317R
Assets
Pronoxis holds priority patent applications for compositional matter for highly specific biased FPR1 agonists, with structural differentiation against presently known competitors.
Pronoxis compounds are considered as:
- Unique
- Singe nM EC50
- Selective and biased FPR1 agonists
The patent landscape of FPR modulators has been reviewed:
The competitive landscape of FPR agonists reviewed:
Yung-Fong Tsai, Shun-Chin Yang & Tsong-Long Hwang (2016) Formyl peptide receptor modulators: a patent review and potential applications for inflammatory diseases (2012-2015), Expert Opinion on Therapeutic Patents, 26:10, 1139-1156, DOI: 10.1080/13543776.2016.1216546
Research collaborations
Pronoxis have active international collaborations with both academic groups as well as industrial partners.
NATIONWIDE CHILDREN’S HOSPITAL- Kidney and Urinary Tract Research Center
In a research collaboration with Dr. Juan de Dios Ruiz-Rosado and Dr. Brian Becknell within the Kidney and Urinary Tract Research Center at Nationwide Children’s Hospital, Columbus Ohio – we are jointly studying the immunological mechanism of the role of NOX inhibition as a mechanism for treatment of diseases of the kidney and urinary tract.
In this research project led by Dr. Juan de Dios Ruiz-Rosado, we are exploring the potential anti-bacterial properties of Pronoxis FPR specific agonists as potential novel agents to treat urinary tract infections (UTI).
