Novel approaches to inhibitor design for the p110β phosphoinositide 3-kinase

Hashem A. Dbouk, Jonathan M. Backer

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Phosphoinositide (PI) 3-kinases are essential regulators of cellular proliferation, survival, metabolism, and motility that are frequently dysregulated in human disease. The design of inhibitors to target the PI 3-kinase/mTOR pathway is a major area of investigation by both academic laboratories and the pharmaceutical industry. This review focuses on the Class IA PI 3-kinase p110β, which plays a unique role in thrombogenesis and in the growth of tumors with deletion or loss-of-function mutation of the Phosphatase and Tensin Homolog (PTEN) lipid phosphatase. Several p110β-selective inhibitors that target the ATP-binding site in the kinase domain have been identified. However, recent discoveries regarding the regulatory mechanisms that control p110β activity suggest alternative strategies by which to disrupt signaling by this PI 3-kinase isoform. This review summarizes the current status of p110β-specific inhibitors and discusses how these new insights into p110 regulation might be used to devise novel pharmacological inhibitors.

Original languageEnglish (US)
Pages (from-to)149-153
Number of pages5
JournalTrends in Pharmacological Sciences
Volume34
Issue number3
DOIs
StatePublished - Mar 2013

Fingerprint

1-Phosphatidylinositol 4-Kinase
Phosphatidylinositols
Phosphotransferases
Phosphoric Monoester Hydrolases
Drug Industry
Protein Isoforms
Metabolism
Adenosine Triphosphate
Binding Sites
Cell Proliferation
Pharmacology
Tumors
Lipids
Mutation
Survival
Growth
Neoplasms
Pharmaceutical Preparations
Industry

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Novel approaches to inhibitor design for the p110β phosphoinositide 3-kinase. / Dbouk, Hashem A.; Backer, Jonathan M.

In: Trends in Pharmacological Sciences, Vol. 34, No. 3, 03.2013, p. 149-153.

Research output: Contribution to journalArticle

@article{60587b60470f46ecbde524f3dd80ad30,
title = "Novel approaches to inhibitor design for the p110β phosphoinositide 3-kinase",
abstract = "Phosphoinositide (PI) 3-kinases are essential regulators of cellular proliferation, survival, metabolism, and motility that are frequently dysregulated in human disease. The design of inhibitors to target the PI 3-kinase/mTOR pathway is a major area of investigation by both academic laboratories and the pharmaceutical industry. This review focuses on the Class IA PI 3-kinase p110β, which plays a unique role in thrombogenesis and in the growth of tumors with deletion or loss-of-function mutation of the Phosphatase and Tensin Homolog (PTEN) lipid phosphatase. Several p110β-selective inhibitors that target the ATP-binding site in the kinase domain have been identified. However, recent discoveries regarding the regulatory mechanisms that control p110β activity suggest alternative strategies by which to disrupt signaling by this PI 3-kinase isoform. This review summarizes the current status of p110β-specific inhibitors and discusses how these new insights into p110 regulation might be used to devise novel pharmacological inhibitors.",
author = "Dbouk, {Hashem A.} and Backer, {Jonathan M.}",
year = "2013",
month = "3",
doi = "10.1016/j.tips.2012.12.004",
language = "English (US)",
volume = "34",
pages = "149--153",
journal = "Trends in Pharmacological Sciences",
issn = "0165-6147",
publisher = "Elsevier Limited",
number = "3",

}

TY - JOUR

T1 - Novel approaches to inhibitor design for the p110β phosphoinositide 3-kinase

AU - Dbouk, Hashem A.

AU - Backer, Jonathan M.

PY - 2013/3

Y1 - 2013/3

N2 - Phosphoinositide (PI) 3-kinases are essential regulators of cellular proliferation, survival, metabolism, and motility that are frequently dysregulated in human disease. The design of inhibitors to target the PI 3-kinase/mTOR pathway is a major area of investigation by both academic laboratories and the pharmaceutical industry. This review focuses on the Class IA PI 3-kinase p110β, which plays a unique role in thrombogenesis and in the growth of tumors with deletion or loss-of-function mutation of the Phosphatase and Tensin Homolog (PTEN) lipid phosphatase. Several p110β-selective inhibitors that target the ATP-binding site in the kinase domain have been identified. However, recent discoveries regarding the regulatory mechanisms that control p110β activity suggest alternative strategies by which to disrupt signaling by this PI 3-kinase isoform. This review summarizes the current status of p110β-specific inhibitors and discusses how these new insights into p110 regulation might be used to devise novel pharmacological inhibitors.

AB - Phosphoinositide (PI) 3-kinases are essential regulators of cellular proliferation, survival, metabolism, and motility that are frequently dysregulated in human disease. The design of inhibitors to target the PI 3-kinase/mTOR pathway is a major area of investigation by both academic laboratories and the pharmaceutical industry. This review focuses on the Class IA PI 3-kinase p110β, which plays a unique role in thrombogenesis and in the growth of tumors with deletion or loss-of-function mutation of the Phosphatase and Tensin Homolog (PTEN) lipid phosphatase. Several p110β-selective inhibitors that target the ATP-binding site in the kinase domain have been identified. However, recent discoveries regarding the regulatory mechanisms that control p110β activity suggest alternative strategies by which to disrupt signaling by this PI 3-kinase isoform. This review summarizes the current status of p110β-specific inhibitors and discusses how these new insights into p110 regulation might be used to devise novel pharmacological inhibitors.

UR - http://www.scopus.com/inward/record.url?scp=84874652531&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84874652531&partnerID=8YFLogxK

U2 - 10.1016/j.tips.2012.12.004

DO - 10.1016/j.tips.2012.12.004

M3 - Article

VL - 34

SP - 149

EP - 153

JO - Trends in Pharmacological Sciences

JF - Trends in Pharmacological Sciences

SN - 0165-6147

IS - 3

ER -