HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

PI3K isoform-selective inhibitors: next-generation targeted cancer therapies.

Abstract
The pivotal roles of phosphatidylinositol 3-kinases (PI3Ks) in human cancers have inspired active development of small molecules to inhibit these lipid kinases. However, the first-generation pan-PI3K and dual-PI3K/mTOR inhibitors have encountered problems in clinical trials, with limited efficacies as a monotherapeutic agent as well as a relatively high rate of side effects. It is increasingly recognized that different PI3K isoforms play non-redundant roles in particular tumor types, which has prompted the development of isoform-selective inhibitors for pre-selected patients with the aim for improving efficacy while decreasing undesirable side effects. The success of PI3K isoform-selective inhibitors is represented by CAL101 (Idelalisib), a first-in-class PI3Kδ-selective small-molecule inhibitor that has been approved by the FDA for the treatment of chronic lymphocytic leukemia, indolent B-cell non-Hodgkin's lymphoma and relapsed small lymphocytic lymphoma. Inhibitors targeting other PI3K isoforms are also being extensively developed. This review focuses on the recent progress in development of PI3K isoform-selective inhibitors for cancer therapy. A deeper understanding of the action modes of novel PI3K isoform-selective inhibitors will provide valuable information to further validate the concept of targeting specific PI3K isoforms, while the identification of biomarkers to stratify patients who are likely to benefit from the therapy will be essential for the success of these agents.
AuthorsXiang Wang, Jian Ding, Ling-hua Meng
JournalActa pharmacologica Sinica (Acta Pharmacol Sin) Vol. 36 Issue 10 Pg. 1170-6 (Oct 2015) ISSN: 1745-7254 [Electronic] United States
PMID26364801 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
Chemical References
  • Antineoplastic Agents
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Isoforms
  • Protein Kinase Inhibitors
  • Purines
  • Quinazolinones
  • idelalisib
Topics
  • Animals
  • Antineoplastic Agents (pharmacology, therapeutic use)
  • Humans
  • Molecular Targeted Therapy (methods)
  • Neoplasms (drug therapy, enzymology, metabolism)
  • Phosphatidylinositol 3-Kinases (metabolism)
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Isoforms (antagonists & inhibitors, metabolism)
  • Protein Kinase Inhibitors (pharmacology, therapeutic use)
  • Purines (pharmacology, therapeutic use)
  • Quinazolinones (pharmacology, therapeutic use)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: