Abstract：
INTRODUCTION:The alpha isoform of the class 1A family of phosphatidylinositol 3-kinases (PI3Kα) has been extensively studied and exploited as a target for cancer drugs. A large number of compounds, from a wide variety of structural scaffolds, are in development. There is an ongoing debate about the desirability for selectivity between PI3Kα and the other isoforms. AREAS COVERED:The article briefly outlines the nature and role of the class 1A PI3K in cell signalling and provides a table of representative inhibitors of these enzymes that have proceeded to clinical trial, with literature data on their isoform selectivity. It covers the published patent literature from 2011 to 2012 (search completed in December 2012), with a particular focus on compounds with a level of selective inhibition of PI3Kα. In most cases, representative examples of claimed compounds and data on their inhibitory effects are provided. EXPERT OPINION:Features of the development of PI3K inhibitors to date have been the plasticity of the enzymes, which possess binding sites for a bewildering number of small molecule scaffolds, and the need to determine the optimal patterns of selectivity between both the PI3K isoforms and the related downstream serine/threonine kinase mammalian target of rapamycin (mTOR) for therapeutic effect. Both themes are apparent in the recent patents reviewed here, with a wide variety of drug types, including variations on existing scaffolds and completely new ones, being evident. While many of these are dual PI3K/mTOR inhibitors, the PI3Kα-selective pyrido[2,3-b]pyrazine heterocycles reported by Intellikine and the (thiazolyl)pyrrolidinecarboxamides of Novartis are of particular interest.
journal_name
Expert Opin Ther Patjournal_title
Expert opinion on therapeutic patentsauthors
Denny WAdoi
10.1517/13543776.2013.779673subject
Has Abstractpub_date
2013-07-01 00:00:00pages
789-99issue
7eissn
1354-3776issn
1744-7674journal_volume
23pub_type
杂志文章,评审abstract：INTRODUCTION:Nuclear factor (NF)-κB, as transcription factor, is linked to the expression of various genes and plays an essential role in immune and inflammatory responses. Abnormal NF-κB signaling results in human diseases, such as immune disorders, inflammation and various cancers. Therefore, regulation of NF-κB may ...
journal_title：Expert opinion on therapeutic patents
pub_type： 杂志文章,评审
doi：10.1517/13543776.2011.638285
更新日期：2011-12-01 00:00:00
abstract：INTRODUCTION:Today, over 20 million people suffer from Alzheimer's disease (AD) worldwide. AD has become a critical issue to human health, especially in aging societies, and therefore it is a research hotspot in the global scientific community. The technology flow method differs from traditional reviews generating an i...
journal_title：Expert opinion on therapeutic patents
pub_type： 杂志文章,评审
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journal_title：Expert opinion on therapeutic patents
pub_type： 杂志文章,评审
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更新日期：2018-06-01 00:00:00
abstract：INTRODUCTION:Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that localizes at sites of cell adhesion to the extracellular matrix (ECM) and mediates signalling events downstream of integrin engagement of the ECM. FAK is known to regulate cell survival, proliferation and migration. AREAS COVERED:FAK expre...
journal_title：Expert opinion on therapeutic patents
pub_type： 杂志文章,评审
doi：10.1080/13543776.2018.1414183
更新日期：2018-02-01 00:00:00
abstract：INTRODUCTION:In the last 10 years, nutraceuticals have grown in interest to researchers, industry, and consumers and are now familiar in the collective imagination as a tool for preventing the onset of a disease. Often nutraceuticals are confused with biologically active phytochemicals/botanicals which can have health ...
journal_title：Expert opinion on therapeutic patents
pub_type： 杂志文章,评审
doi：10.1080/13543776.2018.1552260
更新日期：2018-12-01 00:00:00
abstract：INTRODUCTION:Benzoxaborole is a versatile boron-heterocyclic scaffold which has found in the last 10 years a broad spectrum of applications in medicinal chemistry, due to its physicochemical and drug-like properties. Use of benzoxaborole moiety in the design of compounds led to the discovery of new classes of anti-bact...
journal_title：Expert opinion on therapeutic patents
pub_type： 杂志文章,评审
doi：10.1080/13543776.2018.1473379
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journal_title：Expert opinion on therapeutic patents
pub_type： 杂志文章,评审
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更新日期：2009-02-01 00:00:00
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journal_title：Expert opinion on therapeutic patents
pub_type： 杂志文章
doi：10.1517/13543770902721279
更新日期：2009-04-01 00:00:00
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journal_title：Expert opinion on therapeutic patents
pub_type： 杂志文章
doi：10.1517/13543770802688909
更新日期：2009-03-01 00:00:00
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journal_title：Expert opinion on therapeutic patents
pub_type： 杂志文章,评审
doi：10.1517/13543776.2012.730521
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abstract：IMPORTANCE TO THE FIELD:Leukotrienes (LTs) are pivotal lipid mediators of inflammation and allergy and results from recent studies also suggest roles of LTs in cardiovascular diseases, cancer and osteoporosis. 5-Lipoxygenase (5-LO) catalyzes the first step in the biosynthesis of LTs from arachidonic acid, and based on ...
journal_title：Expert opinion on therapeutic patents
pub_type： 杂志文章,评审
doi：10.1517/13543771003602012
更新日期：2010-03-01 00:00:00
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journal_title：Expert opinion on therapeutic patents
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doi：10.1517/13543770802603577
更新日期：2009-01-01 00:00:00
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journal_title：Expert opinion on therapeutic patents
pub_type： 杂志文章
doi：10.1517/13543776.16.9.1321
更新日期：2006-09-01 00:00:00
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journal_title：Expert opinion on therapeutic patents
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abstract：INTRODUCTION:HIV/AIDS is one of the most devastating diseases in the world affecting > 40 million people worldwide. Morbidity and mortality from AIDS are significantly reduced due to the advent of highly active antiretroviral therapy (HAART). Long-term toxicity, emergence of drug resistant HIV strains and drug-drug int...
journal_title：Expert opinion on therapeutic patents
pub_type： 杂志文章,评审
doi：10.1517/13543776.2011.542412
更新日期：2011-02-01 00:00:00
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journal_title：Expert opinion on therapeutic patents
pub_type： 杂志文章,评审
doi：10.1080/13543776.2017.1296950
更新日期：2017-08-01 00:00:00
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journal_title：Expert opinion on therapeutic patents
pub_type： 杂志文章,评审
doi：10.1080/13543776.2020.1742324
更新日期：2020-06-01 00:00:00
abstract：:In addition to its central role in haemostasis and wound healing, thrombin activates platelets and smooth muscle cells by proteolytic activation of cell surface protease-activated receptor-1 (PAR-1), which is also known as the thrombin receptor. Thrombin is the most potent activator of human platelets and, as such, a ...
journal_title：Expert opinion on therapeutic patents
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doi：10.1517/13543776.16.4.493
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journal_title：Expert opinion on therapeutic patents
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journal_title：Expert opinion on therapeutic patents
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doi：10.1517/13543770902858824
更新日期：2009-05-01 00:00:00
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journal_title：Expert opinion on therapeutic patents
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journal_title：Expert opinion on therapeutic patents
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journal_title：Expert opinion on therapeutic patents
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更新日期：2006-02-01 00:00:00
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journal_title：Expert opinion on therapeutic patents
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doi：10.1517/13543776.2011.577071
更新日期：2011-06-01 00:00:00
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journal_title：Expert opinion on therapeutic patents
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更新日期：2016-07-01 00:00:00
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journal_title：Expert opinion on therapeutic patents
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更新日期：2016-01-01 00:00:00
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journal_title：Expert opinion on therapeutic patents
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journal_title：Expert opinion on therapeutic patents
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更新日期：2013-11-01 00:00:00
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journal_title：Expert opinion on therapeutic patents
pub_type： 杂志文章,评审
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更新日期：2009-10-01 00:00:00
abstract：INTRODUCTION:The appetite stimulating effects of melanin-concentrating hormone (MCH) continues to be of high interest, and there is substantial support to investigate the use of MCH 1-receptor antagonists for the treatment of obesity. Other areas of potential use for MCH 1-receptor antagonists include depression and an...
journal_title：Expert opinion on therapeutic patents
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doi：10.1517/13543776.2011.575063
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