Title:Recent Advances in PI3 Kinase Inhibitors: Anticancer Activities and
Structure-Activity Relationships
Volume: 22
Issue: 16
Author(s): Vivek Asati*, Arjun Anant, Debarshi Kar Mahapatra and Sanjay Kumar Bharti*
Affiliation:
- Department of Pharmaceutical Chemistry, ISF College of Pharmacy, Moga, Punjab, India
- Institute of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya, Bilaspur, Chhattisgarh, India
Keywords:
PI3K, proliferation, kinase, anticancer agents, signaling pathways, SAR.
Abstract: Phosphatidyl-inositol-3-kinase (PI3K) has emerged as a potential therapeutic target for the
development of novel anticancer drugs. The dysregulation of PI3K has been associated with many
human malignancies such as breast, colon, endometrial, brain, and prostate cancers. The PI3K kinases
in their different isoforms, namely α, β, δ, and γ, encode PIK3CA, PIK3CB, PIK3CD, and PIK3CG
genes. Specific gene mutation or overexpression of the protein is responsible for the therapeutic failure
of current therapeutics. Recently, various PI3K signaling pathway inhibitors have been identified,
which showed promising therapeutic results by acting on specific isoforms of the kinase too. Several
inhibitors containing medicinally privileged scaffolds like oxadiazole, pyrrolotriazine, quinazoline,
quinazolinone, quinazoline-chalcone hybrids, quinazoline-sulfonamide, pyrazolochalcone, quinolone
hydroxamic acid, benzofuropyridinone, imidazopyridine, benzoxazines, dibenzoxanthene, indoloderivatives,
benzimidazole, and benzothiazine derivatives have been developed to target the PI3K pathway
and/or a specific isoform. The PI3K inhibitors under clinical trial studies include GDC-0032,
INK1117 for PI3K-α, and AZD8186 for PI3K-β. This review primarily focuses on the structural insights,
anticancer activities, and structure-activity relationship (SARs) studies of recent PI3K inhibitors,
including their clinical stages of development and therapeutic values.
