Class II but Not Second Class-Prospects for the Development of Class II PI3K Inhibitors

Simon J Mountford; Zhaohua Zheng; Krithika Sundaram; Ian G Jennings; Justin R Hamilton; Philip E Thompson

doi:10.1021/ml500354e

Class II but Not Second Class-Prospects for the Development of Class II PI3K Inhibitors

ACS Med Chem Lett. 2014 Sep 24;6(1):3-6. doi: 10.1021/ml500354e. eCollection 2015 Jan 8.

Authors

Simon J Mountford¹, Zhaohua Zheng², Krithika Sundaram¹, Ian G Jennings¹, Justin R Hamilton³, Philip E Thompson¹

Affiliations

¹ Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus) , 381 Royal Parade, Parkville, Victoria 3052, Australia.
² Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus) , 381 Royal Parade, Parkville, Victoria 3052, Australia ; Australian Centre for Blood Diseases and Department of Clinical Haematology, L6, Monash University , 89 Commerical Road , Prahran, Victoria 3181, Australia.
³ Australian Centre for Blood Diseases and Department of Clinical Haematology, L6, Monash University , 89 Commerical Road , Prahran, Victoria 3181, Australia.

Abstract

The Class II PI3 kinases are emerging from the shadows of their Class I cousins. The data emerging from PIK3C2 genetic modification studies and from siRNA knockdown suggest important roles in physiology and pathology. With some well-studied Class I isoform inhibitors showing strong Class II activity and a wealth of crystallographic information available, the structural similarity of these isoforms to Class I provides both the opportunity and the challenge in design of selective pharmacological inhibitors.

Keywords: Class II; PI3 kinase; isoform selectivity.