Abstract
The serine/threonine kinase Akt, also known as protein kinase B (PKB), plays a key role in cell survival and proliferation through a number of downstream effectors. Recent studies indicate that unregulated activation of the Phosphatidylinositol 3-kinase (PI3K)/Akt pathway is a prominent feature of many human cancers and Akt is overexpressed or activated in all major cancers. For these reasons, Akt is considered as an attractive target for cancer therapy. In the past few years, several series of compounds with diverse structural features have been reported as Akt inhibitors, such as, ATP-competitive inhibitors, Phosphatidylinositol (PI) analogs, and allosteric inhibitors. Although most of the inhibitors exhibited potent inhibitory activities at nanomolar concentrations against Akt, some of them have shown unfavorable selectivity against other protein kinases especially PKA and PKC. This review will focus on the recent advances in the development and biological evaluation of selective ATP-competitive inhibitors for Akt. We will summarize the novel approaches toward the developments of selective ATP-competitive inhibitors, expecting to give information to design new ATP-competitive inhibitors with high selectivity, bioavailability, and potency.
Keywords: Akt, ATP-competitive inhibitors, PI3K/Akt signaling pathway, selective, Serine, Threonine, Phosphatidylinositol, allosteric inhibitors, downstream effectors, protein kinase B
Mini-Reviews in Medicinal Chemistry
Title: Developments in Selective Small Molecule ATP-Targeting the Serine/Threonine Kinase Akt/PKB
Volume: 11 Issue: 13
Author(s): P. Wang, L. Zhang, Q. Hao and G. Zhao
Affiliation:
Keywords: Akt, ATP-competitive inhibitors, PI3K/Akt signaling pathway, selective, Serine, Threonine, Phosphatidylinositol, allosteric inhibitors, downstream effectors, protein kinase B
Abstract: The serine/threonine kinase Akt, also known as protein kinase B (PKB), plays a key role in cell survival and proliferation through a number of downstream effectors. Recent studies indicate that unregulated activation of the Phosphatidylinositol 3-kinase (PI3K)/Akt pathway is a prominent feature of many human cancers and Akt is overexpressed or activated in all major cancers. For these reasons, Akt is considered as an attractive target for cancer therapy. In the past few years, several series of compounds with diverse structural features have been reported as Akt inhibitors, such as, ATP-competitive inhibitors, Phosphatidylinositol (PI) analogs, and allosteric inhibitors. Although most of the inhibitors exhibited potent inhibitory activities at nanomolar concentrations against Akt, some of them have shown unfavorable selectivity against other protein kinases especially PKA and PKC. This review will focus on the recent advances in the development and biological evaluation of selective ATP-competitive inhibitors for Akt. We will summarize the novel approaches toward the developments of selective ATP-competitive inhibitors, expecting to give information to design new ATP-competitive inhibitors with high selectivity, bioavailability, and potency.
Export Options
About this article
Cite this article as:
Wang P., Zhang L., Hao Q. and Zhao G., Developments in Selective Small Molecule ATP-Targeting the Serine/Threonine Kinase Akt/PKB, Mini-Reviews in Medicinal Chemistry 2011; 11 (13) . https://dx.doi.org/10.2174/138955711797655380
DOI https://dx.doi.org/10.2174/138955711797655380 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
Call for Papers in Thematic Issues
Bioprospecting of Natural Products as Sources of New Multitarget Therapies
According to the Convention on Biological Diversity, bioprospecting is the exploration of biodiversity and indigenous knowledge to develop commercially valuable products for pharmaceutical and other applications. Bioprospecting involves searching for useful organic compounds in plants, fungi, marine organisms, and microorganisms. Natural products traditionally constituted the primary source of more than ...read more
Computational Frontiers in Medicinal Chemistry
The thematic issue "Computational Frontiers in Medicinal Chemistry" provides a robust platform for delving into state-of-the-art computational methodologies and technologies that significantly propel advancements in medicinal chemistry. This edition seeks to amalgamate top-tier reviews spotlighting the latest trends and breakthroughs in the fusion of computational approaches, including artificial intelligence (AI) ...read more
Natural Products and Dietary Supplements in Alleviation of Metabolic, Cardiovascular, and Neurological Disorders
Metabolic disorders like diabetes, obesity, inflammation, oxidative stress, cancer etc, cardiovascular disorders like angina, myocardial infarction, congestive heart failure etc as well as neurological disorders like Alzheimer?s, Parkinson?s, Epilepsy, Depression, etc are the global burden. They covered the major segment of the diseases and disorders from which the human community ...read more
Natural Products in Drug Discovery
Natural products have always been one of the important ways of drug discovery due to their novel skeleton and diverse functional group characteristics. According to statistics, between 1981 and 2019, the FDA approved a total of 1,394 small molecule drugs for marketing, of which 930 marketed drugs originated from the ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Pharmacological and Biological Activities of Xanthones
Anti-Infective Agents in Medicinal Chemistry Anticholinesterase and Pharmacokinetic Profile of Phenserine in Healthy Elderly Human Subjects
Current Alzheimer Research Cutaneous Neurovascular Interaction Involved in Tactile Sensation
Cardiovascular & Hematological Agents in Medicinal Chemistry Angiogenesis and the Heart
Recent Patents on Cardiovascular Drug Discovery S-Nitrosylation and Attenuation of Excessive Calcium Flux by Pentacycloundecane Derivatives
Medicinal Chemistry The Renin Angiotensin System in the Regulation of Angiogenesis
Current Pharmaceutical Design New Pharmacologic Horizons in the Treatment of Benign Prostatic Hyperplasia
Current Drug Therapy Safety of Nanoparticles in Medicine
Current Drug Targets Nitric Oxide and Dietary Factors: Part III Minerals, Vitamins and Other Dietary and Lifestyle Factors
Vascular Disease Prevention (Discontinued) Mastering the Treatment of Diabetes Mellitus Type 1 in Childhood and Adolescence
Current Pediatric Reviews Current and Future Prospective of a Versatile Moiety: Imidazole
Current Drug Targets Ibubrofen in the Treatment of Patent Ductus Arteriosus in Preterm Infants: What We Know, What We Still Do Not Know
Current Pharmaceutical Design Stevia as a Natural Sweetener: A Review
Cardiovascular & Hematological Agents in Medicinal Chemistry Synthesis and Characterization of Oxazolopyridine and Benzoxazole Derivatives
Letters in Organic Chemistry Losartan Chemistry and Its Effects via AT1 Mechanisms in the Kidney
Current Medicinal Chemistry Protective Effects of Curcumin against Iron-induced Toxicity
Current Pharmaceutical Biotechnology Pharmacologic Targeting of Endothelial Progenitor Cells
Cardiovascular & Hematological Disorders-Drug Targets Vasopressin and Oxytocin in Control of the Cardiovascular System
Current Neuropharmacology Bortezomib – First Therapeutic Proteasome Inhibitor for Cancer Therapy: A Review of Patent Literature
Recent Patents on Anti-Cancer Drug Discovery The Role of Niacin in Lipid-lowering Treatment: Are we Aiming Too High?
Current Pharmaceutical Design