Dr.T の薬学コラム

Perspective

The phosphoinositide 3-kinases (PI3Ks) are a family of lipid kinases central to regulating a wide range of important intracellular processes.

Despite the vast knowledge around class I PI3Ks,

the class II PI3Ks have been neglected, seemingly only due to the chronology of their discovery.

Here we focus on the cellular functions of the three class II PI3K isoforms, PI3KC2α, PI3KC2β, and PI3KC2γ,

in different cell systems and underline the emerging importance of these enzymes in different physiological and pathological contexts.

We provide an overview on the current development of class II PI3 kinase inhibitors and outline the potential use for such inhibitors. The field is in its infancy as compared to their class I counterparts. Nevertheless, recent advances in understanding the roles of class II PI3 kinases in different pathological contexts is leading to an increased interest in the development of specific inhibitors that can provide potential novel pharmacological tools.

Class II Phosphoinositide 3-Kinases as Novel Drug Targets

Miniperspective

Marco Falasca^*^†, Justin R. Hamilton^‡, Maria Selvadurai^‡, Krithika Sundaram^§, Aleksandra Adamska^†, and Philip E. Thompson^§

^† Metabolic Signalling Group, School of Biomedical Sciences, CHIRI Biosciences, Curtin University, Perth, Western Australia 6845, Australia

^‡ Australian Centre for Blood Diseases and Department of Clinical Haematology, Monash University, 99 Commercial Road, Melbourne, Victoria 3004, Australia

^§ Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Parade, Parkville, Victoria 3052, Australia

J. Med. Chem., Article ASAP

DOI: 10.1021/acs.jmedchem.6b00963

Publication Date (Web): September 20, 2016

*Phone +61 08 92669712. E-mail: marco.falasca@curtin.edu.au.

Biography

Marco Falasca was educated in Italy. He then was involved in postdoctoral training at New York University from 1995 to 1998. Prof. Falasca took up a position as Head of the Unit of Physiopathology of Cell Signalling within the Consorzio Mario Negri Sud in 1998. In 2001 he moved to London where he was appointed as Principal Research Fellow at the University College London. In 2007 he was appointed as Professor of Molecular Pharmacology at the Queen Mary University of London. In 2014 he was appointed as Professor in Metabolism at the School of Biomedical Sciences, Curtin University, Perth, Australia. Research in his lab is mostly focused on intracellular signals regulated by specific lipids that act as “second messengers” such as those produced by PI3Ks.

Biography

Justin R. Hamilton obtained his Ph.D. in Pharmacology in 2001 from The University of Melbourne, Australia, and completed postdoctoral studies at The University of California, San Francisco, U.S., with Prof. Shaun Coughlin, from 2001 to 2006. He then moved back to Australia to establish a research group at The Australian Centre for Blood Diseases, Monash University, where he is currently a Future Fellow of the Australian Research Council and Head of the Platelets & Thrombosis Laboratory. His group studies the role of platelets in hemostasis, thrombosis, and inflammatory conditions, with a focus on intracellular signaling effectors such as class II PI3Ks.

Biography

Maria Selvadurai is a medical student and Ph.D. candidate at The Australian Centre for Blood Diseases, Monash University, under the supervision of Justin Hamilton. Maria is researching the cellular effects of class II PI3Ks and the biological implications of class II PI3K inhibitors. She has an interest in platelet biology, clinical platelet disorders, and the development of novel antiplatelet drugs for improved antithrombotic therapy and has previously studied at the Etablissement Francais du Sang (Alsace), Strasbourg, France, in the group of Prof. Christian Gachet.

Biography

Krithika Sundaram obtained her B.Sc. in Microbiology from Osmania University (India) and M.S. in Biotechnology from Victoria University (Australia). She obtained her Ph.D. degree from Monash University in May 2016. Her thesis was entitled “Structure-Based Studies in the Development of Anticancer Enzyme Inhibitors Including the Study of Class II PI3KC2β”.

Biography

Aleksandra Adamska is a Ph.D. student at The Curtin Health Innovation Research Institute, School of Biomedical Sciences, Curtin University, where she is studying under the supervision of Prof. Marco Falasca. Aleksandra graduated from Wroclaw University of Technology (Wroclaw, Poland) in the field of pharmaceutical biotechnology. She also completed a 1-year internship at The University of Chicago in the group of Dr. Anthony Kossiakoff. Currently Aleksandra’s interests are focused on the investigation of GPCRs and ABC transporters as potential targets in pancreatic cancer therapy.

Biography

Philip E. Thompson is an Associate Professor in Medicinal Chemistry at Monash University. He obtained his B.Sc.(Hons.) and Ph.D. from the University of Melbourne. In his research career, he has studied an array of topics with over 100 publications in international journals of diverse disciplines. He spent 5 years at the biotechnology company Kinacia, which developed the first PI3Kβ-selective inhibitors, and has continued to study PI3K in an academic setting. His other area of active interest is in peptide science with recent focus on polymyxin analogues and neuropeptide Y receptor ligands.

Abstract

The phosphoinositide 3-kinases (PI3Ks) are a family of lipid kinases central to regulating a wide range of important intracellular processes. Despite the vast knowledge around class I PI3Ks, the class II PI3Ks have been neglected, seemingly only due to the chronology of their discovery. Here we focus on the cellular functions of the three class II PI3K isoforms, PI3KC2α, PI3KC2β, and PI3KC2γ, in different cell systems and underline the emerging importance of these enzymes in different physiological and pathological contexts. We provide an overview on the current development of class II PI3 kinase inhibitors and outline the potential use for such inhibitors. The field is in its infancy as compared to their class I counterparts. Nevertheless, recent advances in understanding the roles of class II PI3 kinases in different pathological contexts is leading to an increased interest in the development of specific inhibitors that can provide potential novel pharmacological tools.

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Dr.T の薬学コラム

2016年11月5日土曜日

Perspective

The phosphoinositide 3-kinases (PI3Ks) are a family of lipid kinases central to regulating a wide range of important intracellular processes.

Despite the vast knowledge around class I PI3Ks,

the class II PI3Ks have been neglected, seemingly only due to the chronology of their discovery.

Here we focus on the cellular functions of the three class II PI3K isoforms, PI3KC2α, PI3KC2β, and PI3KC2γ,

in different cell systems and underline the emerging importance of these enzymes in different physiological and pathological contexts.

Class II Phosphoinositide 3-Kinases as Novel Drug Targets

Miniperspective

Abstract

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2016年11月5日土曜日

Perspective

The phosphoinositide 3-kinases (PI3Ks) are a family of lipid kinases central to regulating a wide range of important intracellular processes.

Despite the vast knowledge around class I PI3Ks,

the class II PI3Ks have been neglected, seemingly only due to the chronology of their discovery.

Here we focus on the cellular functions of the three class II PI3K isoforms, PI3KC2α, PI3KC2β, and PI3KC2γ,

in different cell systems and underline the emerging importance of these enzymes in different physiological and pathological contexts.

Class II Phosphoinositide 3-Kinases as Novel Drug Targets

Miniperspective

Abstract

Other ACS content by these authors:

Related Content:

Metrics

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