Isoform selective inhibition of STAT1 or STAT3 homo-dimerization via peptidomimetic probes: Structural recognition of STAT SH2 domains

Patrick T. Gunning; William P. Katt; Matthew Glenn; Khandaker Siddique; Joon S. Kim; Richard Jove; Saïd M. Sebti; James Turkson; Andrew D. Hamilton

doi:10.1016/j.bmcl.2007.01.077

Isoform selective inhibition of STAT1 or STAT3 homo-dimerization via peptidomimetic probes: Structural recognition of STAT SH2 domains

Patrick T. Gunning, William P. Katt, Matthew Glenn, Khandaker Siddique, Joon S. Kim, Richard Jove, Saïd M. Sebti, James Turkson, Andrew D. Hamilton

Chemistry

Research output: Contribution to journal › Article › peer-review

Abstract

The identification of constitutively activated STAT (Signal Transducers and Activators of Transcription) proteins in aberrant cell signaling pathways has led to investigations targeting the selective disruption of specific STAT isoforms directly associated with oncogenisis. We have identified, through the design of a library of peptidomimetic inhibitors, agents that selectively disrupt STAT1 or STAT3 homo-dimerization at low micromolar concentrations. ISS840 has 20-fold higher inhibition of STAT1 homo-dimerization (IC₅₀ value of 31 μM) relative to STAT3 (IC₅₀ value of 560 μM).

Original language	English (US)
Pages (from-to)	1875-1878
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	17
Issue number	7
DOIs	https://doi.org/10.1016/j.bmcl.2007.01.077
State	Published - Apr 1 2007

Keywords

Anti-cancer
Inhibitors
Peptidomimetics
SH2 domain recognition
STAT1
STAT3

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

Access to Document

10.1016/j.bmcl.2007.01.077

Cite this

@article{efa5146c45ad485eac7c4ca9b08aa7fe,

title = "Isoform selective inhibition of STAT1 or STAT3 homo-dimerization via peptidomimetic probes: Structural recognition of STAT SH2 domains",

abstract = "The identification of constitutively activated STAT (Signal Transducers and Activators of Transcription) proteins in aberrant cell signaling pathways has led to investigations targeting the selective disruption of specific STAT isoforms directly associated with oncogenisis. We have identified, through the design of a library of peptidomimetic inhibitors, agents that selectively disrupt STAT1 or STAT3 homo-dimerization at low micromolar concentrations. ISS840 has 20-fold higher inhibition of STAT1 homo-dimerization (IC50 value of 31 μM) relative to STAT3 (IC50 value of 560 μM).",

keywords = "Anti-cancer, Inhibitors, Peptidomimetics, SH2 domain recognition, STAT1, STAT3",

author = "Gunning, {Patrick T.} and Katt, {William P.} and Matthew Glenn and Khandaker Siddique and Kim, {Joon S.} and Richard Jove and Sebti, {Sa{\"i}d M.} and James Turkson and Hamilton, {Andrew D.}",

year = "2007",

month = apr,

day = "1",

doi = "10.1016/j.bmcl.2007.01.077",

language = "English (US)",

volume = "17",

pages = "1875--1878",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Limited",

number = "7",

}

TY - JOUR

T1 - Isoform selective inhibition of STAT1 or STAT3 homo-dimerization via peptidomimetic probes

T2 - Structural recognition of STAT SH2 domains

AU - Gunning, Patrick T.

AU - Katt, William P.

AU - Glenn, Matthew

AU - Siddique, Khandaker

AU - Kim, Joon S.

AU - Jove, Richard

AU - Sebti, Saïd M.

AU - Turkson, James

AU - Hamilton, Andrew D.

PY - 2007/4/1

Y1 - 2007/4/1

N2 - The identification of constitutively activated STAT (Signal Transducers and Activators of Transcription) proteins in aberrant cell signaling pathways has led to investigations targeting the selective disruption of specific STAT isoforms directly associated with oncogenisis. We have identified, through the design of a library of peptidomimetic inhibitors, agents that selectively disrupt STAT1 or STAT3 homo-dimerization at low micromolar concentrations. ISS840 has 20-fold higher inhibition of STAT1 homo-dimerization (IC50 value of 31 μM) relative to STAT3 (IC50 value of 560 μM).

AB - The identification of constitutively activated STAT (Signal Transducers and Activators of Transcription) proteins in aberrant cell signaling pathways has led to investigations targeting the selective disruption of specific STAT isoforms directly associated with oncogenisis. We have identified, through the design of a library of peptidomimetic inhibitors, agents that selectively disrupt STAT1 or STAT3 homo-dimerization at low micromolar concentrations. ISS840 has 20-fold higher inhibition of STAT1 homo-dimerization (IC50 value of 31 μM) relative to STAT3 (IC50 value of 560 μM).

KW - Anti-cancer

KW - Inhibitors

KW - Peptidomimetics

KW - SH2 domain recognition

KW - STAT1

KW - STAT3

UR - http://www.scopus.com/inward/record.url?scp=33847682326&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33847682326&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2007.01.077

DO - 10.1016/j.bmcl.2007.01.077

M3 - Article

C2 - 17336521

AN - SCOPUS:33847682326

SN - 0960-894X

VL - 17

SP - 1875

EP - 1878

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 7

ER -

Isoform selective inhibition of STAT1 or STAT3 homo-dimerization via peptidomimetic probes: Structural recognition of STAT SH2 domains

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this