Preclinical characterization of CPL302-253, a selective inhibitor of PI3Kδ, as the candidate for the inhalatory treatment and prevention of Asthma

PLoS One. 2020 Jul 23;15(7):e0236159. doi: 10.1371/journal.pone.0236159. eCollection 2020.

Abstract

Asthma is a common chronic inflammatory disease. Although effective asthma therapies are available, part of asthmatic population do not respond to these treatment options. In this work we present the result of development of CPL302-253 molecule, a selective PI3Kδ inhibitor. This molecule is intended to be a preclinical candidate for dry powder inhalation in asthma treatment. Studies we performed showed that this molecule is safe and effective PI3Kδ inhibitor that can impact many immune functions. We developed a short, 15-day HDM induced asthma mouse model, in which we showed that CPL302-253 is able to block inflammatory processes leading to asthma development in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Animals
  • Anti-Asthmatic Agents / administration & dosage*
  • Anti-Asthmatic Agents / pharmacology*
  • Anti-Asthmatic Agents / therapeutic use
  • Asthma / drug therapy*
  • Asthma / prevention & control*
  • Cell Line
  • Class I Phosphatidylinositol 3-Kinases / antagonists & inhibitors*
  • Dry Powder Inhalers
  • Enzyme Inhibitors / administration & dosage*
  • Enzyme Inhibitors / pharmacology*
  • Enzyme Inhibitors / therapeutic use
  • Female
  • Humans
  • Mice

Substances

  • Anti-Asthmatic Agents
  • Enzyme Inhibitors
  • Class I Phosphatidylinositol 3-Kinases

Grants and funding

The work presented in this manuscript was funded by commercial companies: Celon Pharma and LabMagister Training and Science Ltd. The work was supported by Narodowe Centrum Badan i Rozwoju (grant nr POIR.01.01.01-00-1341/15). PG, KG, MB, JD, JHK, KM, DS, KD, JP, BMZ and MW are employees of Celon Pharma. AH and EGH are employees of LabMagister Training and Science Ltd. The funders provided support in the form of salaries for authors PG, KG, MB, JD, JHK, KM, DS, KD, JP, BMZ, MW, AH and EGH, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.