Considerable biological evidence has accumulated in support of nominating the Class I PI3Ks (phosphoinositide 3-kinases) as excellent targets for the development of novel pharmaceuticals to treat cancer and inflammatory disease. Although it remains a goal to deliver compounds with precise PI3K isoform selectivity in order to minimize safety risks, it is not yet certain that this approach will deliver suitable benefit against disease when tested in the clinic. The UCB strategy, therefore, has been to generate a range of compounds covering a broad spectrum of PI3K isoform inhibition. Scaffold diversity has been accomplished by identifying hits using both pharmacophore search and high-throughput screening campaigns, while modulation of potency and isoform selectivity has been achieved through exploratory medicinal chemistry. Simple, high-throughput cell assays relevant to either inflammation or cancer have then been employed to establish a blueprint for defining how isoform selectivity affects biological potency. I will focus on two compounds from our collection: a pan-PI3K inhibitor and UCB1311236, a compound with significant potency against only the PI3Kγ isoform. These examples will be used to illustrate the extent to which isoform selectivity informs on compound potency against other kinases and to highlight the risks and benefits of developing compounds with limited isoform selectivity.
Skip Nav Destination
Article navigation
April 2007
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
Conference Article|
March 20 2007
Exploring the potential of PI3K inhibitors for inflammation and cancer
T. Crabbe
T. Crabbe
1
1UCB, 216 Bath Road, Slough SL1 4EN, U.K.
1email [email protected]
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
November 02 2006
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2007 The Biochemical Society
2007
Biochem Soc Trans (2007) 35 (2): 253–256.
Article history
Received:
November 02 2006
Citation
T. Crabbe; Exploring the potential of PI3K inhibitors for inflammation and cancer. Biochem Soc Trans 1 April 2007; 35 (2): 253–256. doi: https://doi.org/10.1042/BST0350253
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Biochemical Society Member Sign in
Sign InSign in via your Institution
Sign in via your InstitutionGet Access To This Article
Get Email Alerts
Open Access for all
We offer compliant routes for all authors from 2025. With library support, there will be no author nor reader charges in 5 journals. Check here |
![]() |