Research advances on selective phosphatidylinositol 3 kinase δ (PI3Kδ) inhibitors

Bioorg Med Chem Lett. 2020 Oct 1;30(19):127457. doi: 10.1016/j.bmcl.2020.127457. Epub 2020 Aug 2.

Abstract

PI3Kδ in B cells mediates antigen receptor signaling and promote neutrophil chemotaxis. The activation of PI3Kδ can cause mast cell maturation and degranulation, myeloid cell dysfunction, and cytokine release. As a key signal molecule, PI3Kδ interacts with the lipid binding domain of a variety of cellular proteins as a secondary messenger, ultimately affecting a series of significant cellular pathways in disease pathology. Therefore, many research organizations and pharmaceutical companies have studied it to develop effectively selective PI3Kδ inhibitors as therapeutics. This review summarizes research advances in varying chemical classes of selective PI3Kδ inhibitors and the structure-activity relationship, and it mainly focuses on the propeller- versus flat-type class of inhibitors.

Keywords: Chemical structure; Flat-type; PI3Kδ inhibitors; Propeller-type.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Autoimmune Diseases / drug therapy
  • Cell Line, Tumor
  • Class I Phosphatidylinositol 3-Kinases / antagonists & inhibitors*
  • Clinical Trials as Topic
  • Heterocyclic Compounds / chemical synthesis
  • Heterocyclic Compounds / pharmacology
  • Heterocyclic Compounds / therapeutic use*
  • Humans
  • Lung Diseases, Obstructive / drug therapy
  • Molecular Structure
  • Neoplasms / drug therapy
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Heterocyclic Compounds
  • Protein Kinase Inhibitors
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CD protein, human