Inhibitors of Src homology-2 domain containing protein tyrosine phosphatase-2 (Shp2) based on oxindole scaffolds

Harshani R. Lawrence; Roberta Pireddu; Liwei Chen; Yunting Luo; Shen Shu Sung; Ann Marie Szymanski; M. L.Richard Yip; Wayne C. Guida; Saïd M. Sebti; Jie Wu; Nicholas J. Lawrence

doi:10.1021/jm8002526

Inhibitors of Src homology-2 domain containing protein tyrosine phosphatase-2 (Shp2) based on oxindole scaffolds

Harshani R. Lawrence, Roberta Pireddu, Liwei Chen, Yunting Luo, Shen Shu Sung, Ann Marie Szymanski, M. L.Richard Yip, Wayne C. Guida, Saïd M. Sebti, Jie Wu, Nicholas J. Lawrence

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92 Scopus citations

Abstract

Screening of the NCI diversity set of compounds has led to the identification of 5 (NSC-117199), which inhibits the protein tyrosine phosphatase (PTP) Shp2 with an IC₅₀ of 47 μM. A focused library incorporating an isatin scaffold was designed and evaluated for inhibition of Shp2 and Shp1 PTP activities. Several compounds were identified that selectively inhibit Shp2 over Shp1 and PTP1B with low to submicromolar activity. A model for the binding of the active compounds is proposed.

Original language	English (US)
Pages (from-to)	4948-4956
Number of pages	9
Journal	Journal of Medicinal Chemistry
Volume	51
Issue number	16
DOIs	https://doi.org/10.1021/jm8002526
State	Published - Aug 28 2008

All Science Journal Classification (ASJC) codes

Molecular Medicine
Drug Discovery

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title = "Inhibitors of Src homology-2 domain containing protein tyrosine phosphatase-2 (Shp2) based on oxindole scaffolds",

abstract = "Screening of the NCI diversity set of compounds has led to the identification of 5 (NSC-117199), which inhibits the protein tyrosine phosphatase (PTP) Shp2 with an IC50 of 47 μM. A focused library incorporating an isatin scaffold was designed and evaluated for inhibition of Shp2 and Shp1 PTP activities. Several compounds were identified that selectively inhibit Shp2 over Shp1 and PTP1B with low to submicromolar activity. A model for the binding of the active compounds is proposed.",

author = "Lawrence, {Harshani R.} and Roberta Pireddu and Liwei Chen and Yunting Luo and Sung, {Shen Shu} and Szymanski, {Ann Marie} and Yip, {M. L.Richard} and Guida, {Wayne C.} and Sebti, {Sa{\"i}d M.} and Jie Wu and Lawrence, {Nicholas J.}",

year = "2008",

month = aug,

day = "28",

doi = "10.1021/jm8002526",

language = "English (US)",

volume = "51",

pages = "4948--4956",

journal = "Journal of Medicinal Chemistry",

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publisher = "American Chemical Society",

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TY - JOUR

T1 - Inhibitors of Src homology-2 domain containing protein tyrosine phosphatase-2 (Shp2) based on oxindole scaffolds

AU - Lawrence, Harshani R.

AU - Pireddu, Roberta

AU - Chen, Liwei

AU - Luo, Yunting

AU - Sung, Shen Shu

AU - Szymanski, Ann Marie

AU - Yip, M. L.Richard

AU - Guida, Wayne C.

AU - Sebti, Saïd M.

AU - Wu, Jie

AU - Lawrence, Nicholas J.

PY - 2008/8/28

Y1 - 2008/8/28

N2 - Screening of the NCI diversity set of compounds has led to the identification of 5 (NSC-117199), which inhibits the protein tyrosine phosphatase (PTP) Shp2 with an IC50 of 47 μM. A focused library incorporating an isatin scaffold was designed and evaluated for inhibition of Shp2 and Shp1 PTP activities. Several compounds were identified that selectively inhibit Shp2 over Shp1 and PTP1B with low to submicromolar activity. A model for the binding of the active compounds is proposed.

AB - Screening of the NCI diversity set of compounds has led to the identification of 5 (NSC-117199), which inhibits the protein tyrosine phosphatase (PTP) Shp2 with an IC50 of 47 μM. A focused library incorporating an isatin scaffold was designed and evaluated for inhibition of Shp2 and Shp1 PTP activities. Several compounds were identified that selectively inhibit Shp2 over Shp1 and PTP1B with low to submicromolar activity. A model for the binding of the active compounds is proposed.

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AN - SCOPUS:50249093762

SN - 0022-2623

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JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 16

ER -

Inhibitors of Src homology-2 domain containing protein tyrosine phosphatase-2 (Shp2) based on oxindole scaffolds

Abstract

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