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Pharmaceuticals
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PI3 Kinase Inhibitors
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PI3 Kinase Inhibitors

A special issue of Pharmaceuticals (ISSN 1424-8247).

Deadline for manuscript submissions: closed (30 June 2012) | Viewed by 23509

Special Issue Editor

Dr. Philip Thompson

E-Mail Website
Guest Editor
Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical, Sciences, Monash University, Parkville 3052, Australia

Special Issue Information

Dear Colleagues,

Phosphoinositide 3-kinases (PI3K) are important cell signalling enzymes, generating key second messengers that regulate a myriad of cellular functions. In recent years, potential applications for inhibitors have emerged in the treatment of cancer, cardiovascular disease, inflammatory diseases and autoimmune diseases. This special issue hopes to highlight the challenges and lessons learned in going from "hit to lead" and "lead to candidate" when developing targets for PI3K.  Articles that deal with the concepts and results of specific strategic choices in PI3K inhibitor pharmaceutical development are encouraged. These include design approach (eg library screening, structure based design), isoform selectivity, scaffold selection, ADME properties or in vitro/in vivo models. In this issue, I hope novel contributions can be made to the medicinal chemistry knowledge base with original papers or critical reviews.

Dr. Philip Thompson
Guest Editor

Keywords

  • PI3 kinase
  • phosphatidylinositol
  • cell signaling
  • cancer therapeutics
  • lipid kinase
  • inflammation
  • immune disease
  • thrombosis

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Published Papers (2 papers)

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Review

325 KiB  
Review
The Biological Role of PI3K Pathway in Lung Cancer
by Evangelos G. Sarris, Muhammad W. Saif and Kostas N. Syrigos
Pharmaceuticals 2012, 5(11), 1236-1264; https://doi.org/10.3390/ph5111236 - 20 Nov 2012
Cited by 94 | Viewed by 12968
Abstract
Lung cancer is the primary cause of cancer-related mortality worldwide and although improvements in treatment have been achieved over the last few years, long-term survival rates for lung cancer patients remain poor. Therefore, there is an imperative need for molecularly targeted agents that [...] Read more.
Lung cancer is the primary cause of cancer-related mortality worldwide and although improvements in treatment have been achieved over the last few years, long-term survival rates for lung cancer patients remain poor. Therefore, there is an imperative need for molecularly targeted agents that will achieve long-term disease control. Numerous downstream molecular pathways, such as EGF/RAS/RAF/MEK/ERK and PI3K/AKT/mTOR are identified as having a key role in the pathogenesis of various forms of human cancer, including lung cancer. PI3K/AKT/mTOR signal pathway is an important intracellular signal transduction pathway with a significant role in cell proliferation, growth, survival, vesicle trafficking, glucose transport, and cytoskeletal organization. Aberrations in many primary and secondary messenger molecules of this pathway, including mutations and amplifications, are accounted for tumor cell proliferation, inhibition of apoptosis, angiogenesis, metastasis and resistance to chemotherapy-radiotherapy. In this review article, we investigate thoroughly the biological role of PI3K pathway in lung cancer and its contribution in the development of future therapeutic strategies. Full article
(This article belongs to the Special Issue PI3 Kinase Inhibitors)
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Review
The Phosphatidylinositol 3-Kinase/mTor Pathway as a Therapeutic Target for Brain Aging and Neurodegeneration
by David Heras-Sandoval, Evangelina Avila-Muñoz and Clorinda Arias
Pharmaceuticals 2011, 4(8), 1070-1087; https://doi.org/10.3390/ph4081070 - 4 Aug 2011
Cited by 22 | Viewed by 9817
Abstract
Many pathological conditions are associated with phosphatidylinositol 3-kinase (PI3K) dysfunction, providing an incentive for the study of the effects of PI3K modulation in different aspects of diabetes, cancer, and aging. The PI3K/AKT/mTOR pathway is a key transducer of brain metabolic and mitogenic signals [...] Read more.
Many pathological conditions are associated with phosphatidylinositol 3-kinase (PI3K) dysfunction, providing an incentive for the study of the effects of PI3K modulation in different aspects of diabetes, cancer, and aging. The PI3K/AKT/mTOR pathway is a key transducer of brain metabolic and mitogenic signals involved in neuronal proliferation, differentiation, and survival. In several models of neurodegenerative diseases associated with aging, the PI3K/AKT pathway has been found to be dysregulated, suggesting that two or more initiating events may trigger disease formation in an age-related manner. The search for chemical compounds able to modulate the activity of the PI3K/AKT/mTOR pathway is emerging as a potential therapeutic strategy for the treatment and/or prevention of some metabolic defects associated with brain aging. In the current review, we summarize some of the critical actions of PI3K in brain function as well as the evidence of its involvement in aging and Alzheimer’s disease. Full article
(This article belongs to the Special Issue PI3 Kinase Inhibitors)
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