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

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

  • J Med Chem. 2008 Aug 28;51(16):4948-56. doi: 10.1021/jm8002526.
Harshani R Lawrence 1,  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
Affiliations

Affiliation

  • 1 Drug Discovery Program, Moffitt Cancer Center, 12901 Magnolia Drive, Tampa, Florida 33612, USA. Harshani.Lawrence@moffitt.org
PMID: 18680359 DOI: 10.1021/jm8002526
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 microM. 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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