A Perspective Study on the RTK, PI3K, B-Raf, CDK and the Multi-Protein Targeting in Medicinal Chemistry

Chem Biodivers. 2022 Oct;19(10):e202200328. doi: 10.1002/cbdv.202200328. Epub 2022 Oct 17.

Abstract

The cellular signaling pathway components that control the different stages of cell maturation such as RTK, PI3K, B-Raf, and CDK represent crucial antitumor drug targets. The isoform diversity of these components revealed multi-divergent vents for cancer cells to develop several resistance mechanisms against these new selective drug targets. This review article illustrates the complex nature of cancer, moreover, molecular tracing of tumor resistance towards certain signaling pathways was presented. Several crucial interventions in this regard for antitumor agents' development were pointed out. The antitumor activities of several cancer chemotherapies targeting kinases were also discussed with a special focus on the structural bases for the design of protein kinase inhibitors. Additionally, a focused literature survey about the various targeted multi-kinase inhibition approaches as a mean to overcome cancer resistance was also included.

Keywords: B-Raf; PI3K; RTK; anticancer; multi-kinase targeting.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Cell Line, Tumor
  • Chemistry, Pharmaceutical
  • Humans
  • Neoplasms* / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Proto-Oncogene Proteins B-raf / metabolism
  • Proto-Oncogene Proteins B-raf / therapeutic use

Substances

  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins B-raf
  • Protein Kinase Inhibitors
  • Antineoplastic Agents