PI3K Inhibitors for Cancer Therapy: What has been Achieved So Far?

Peng Wu, Tao Liu, Yongzhou Hu

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

PI3K is a large duel lipid and protein kinase that catalyzes phosphorylation of the 3-hydroxyl position of phosphatidylinositides (PIs) and plays a crucial role in the cellular signaling network. Inhibition of the phosphatidylinositol 3-kinase (PI3K) signaling pathway is a newly identified strategy for the discovery and development of certain therapeutic agents. Among the various subtypes of PI3K, class IA PI3K alpha has gained increasing attention as a promising drug target for the treatment of cancer due to its frequent mutations and amplifications in various human cancers. Here, we discuss the insights gained so far relevant to the development of PI3K inhibitors for the treatment of human cancers. Emphasis is on the structure-activity relationship of PI3K inhibitors which bear the most significant PI3K alpha inhibitory activities. We also highlight PI3K inhibitors that are currently under clinical trials for cancers.
Original languageEnglish
JournalCurrent Medicinal Chemistry
Volume16
Issue number8
Pages (from-to)916-930
ISSN0929-8673
DOIs
Publication statusPublished - 2009
Externally publishedYes

Keywords

  • Molecular Medicine
  • Pharmacology
  • Anticancer
  • Clinical trial
  • PI3K inhibitor
  • PI3K��
  • Structure-activity relationship (SAR)
  • 1 (1 cyano 1 methylethyl) 3 methyl 8 (3 quinolinyl)imidazo[4,5 c]quinolin 2(1h,3h) one
  • 2 (4 hydroxyphenyl) 4 morpholinopyrido[3',2':4,5]furo[3,2 d]pyrimidine
  • 2 morpholino 8 phenylchromone
  • 4 morpholino 2 phenylquinazolin 6 ol
  • 7 hydroxystaurosporine
  • 9 (1 anilinoethyl) 7 methyl 2 morpholinopyrido[1,2 a]pyrimidin 4 one
  • antineoplastic agent
  • ap 23576
  • bgt 226
  • carboplatin
  • erlotinib
  • everolimus
  • gdc 0941
  • imidazopyridine derivative
  • morpholine derivative
  • paclitaxel
  • phosphatidylinositol 3 kinase
  • phosphatidylinositol 3 kinase alpha
  • phosphatidylinositol 3 kinase alpha inhibitor
  • phosphatidylinositol 3 kinase inhibitor
  • pik 75
  • px 866
  • pyrido [3',2':4,5]thieno[3,2 d]pyrimidine derivative
  • sf 1126
  • temozolomide
  • temsirolimus
  • unclassified drug
  • unindexed drug
  • wortmannin
  • xl 147
  • xl 765
  • advanced cancer
  • antineoplastic activity
  • breast cancer
  • carcinogenesis
  • chemical modification
  • clinical trial
  • drug bioavailability
  • drug efficacy
  • drug half life
  • drug penetration
  • drug research
  • drug selectivity
  • drug structure
  • drug targeting
  • drug tolerability
  • enzyme activation
  • enzyme inhibition
  • enzyme structure
  • glioblastoma
  • glucose tolerance
  • human
  • hyperglycemia
  • leukocytosis
  • lung cancer
  • lung non small cell cancer
  • malignant neoplastic disease
  • nonhuman
  • ovary cancer
  • review
  • side effect
  • signal transduction
  • solid tumor
  • structure activity relation
  • uterine cervix cancer
  • weight reduction
  • 1-Phosphatidylinositol 3-Kinase
  • Animals
  • Antineoplastic Agents
  • Humans
  • Isoenzymes
  • Neoplasms
  • Protein Kinase Inhibitors
  • Signal Transduction
  • Phosphatidylinositol 3-Kinases
  • EC 2.7.1.- Phosphatidylinositol 3-Kinases
  • BIOCHEMISTRY
  • CHEMISTRY,
  • PHARMACOLOGY
  • PROTEIN-KINASE-B
  • PHOSPHATIDYLINOSITOL 3-KINASE INHIBITOR
  • SQUAMOUS-CELL CARCINOMA
  • PI3-KINASE P110-ALPHA INHIBITORS
  • FORKHEAD TRANSCRIPTION FACTOR
  • GLYCOGEN-SYNTHASE KINASE-3
  • CHRONIC MYELOID-LEUKEMIA
  • PHOSPHOINOSITIDE 3-KINASE
  • BIOLOGICAL EVALUATION
  • PIK3CA GENE
  • PI3K alpha
  • anticancer
  • structure-activity relationship (SAR)
  • cellular signaling network
  • structure-activity relationship
  • cancer Neoplasms (MeSH) neoplastic disease drug therapy
  • Primates Mammalia Vertebrata Chordata Animalia (Animals, Chordates, Humans, Mammals, Primates, Vertebrates) - Hominidae [86215] human common HeLa cell line cell_line human cervical cancer cells
  • Rodentia Mammalia Vertebrata Chordata Animalia (Animals, Chordates, Mammals, Nonhuman Vertebrates, Nonhuman Mammals, Rodents, Vertebrates) - Muridae [86375] mouse common
  • phosphatidylinositide PI3K signaling, phosphorylation
  • phosphatidylinositol 3-kinase-alpha PI3K-alpha inhibitory activity
  • PI3K inhibitors antineoplastic-drug
  • 02506, Cytology - Animal
  • 02508, Cytology - Human
  • 12512, Pathology - Therapy
  • 22002, Pharmacology - General
  • 22005, Pharmacology - Clinical pharmacology
  • 24004, Neoplasms - Pathology, clinical aspects and systemic effects
  • 24008, Neoplasms - Therapeutic agents and therapy
  • Human Medicine, Medical Sciences
  • cancer therapy therapeutic and prophylactic techniques, clinical techniques
  • Oncology

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