Lawrence Harshani R, Pireddu Roberta, Chen Liwei, Luo Yunting, Sung Shen-Shu, Szymanski Ann Marie, Yip M L Richard, Guida Wayne C, Sebti Saïd M, Wu Jie, Lawrence Nicholas J
Drug Discovery Program, Moffitt Cancer Center, 12901 Magnolia Drive, Tampa, Florida 33612, USA.
J Med Chem. 2008 Aug 28;51(16):4948-56. doi: 10.1021/jm8002526. Epub 2008 Aug 5.
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.
对美国国立癌症研究所（NCI）化合物多样性集进行筛选后，已鉴定出5种化合物（NSC - 117199），其对蛋白酪氨酸磷酸酶（PTP）Shp2具有抑制作用，半数抑制浓度（IC50）为47微摩尔。设计并评估了一个包含异吲哚酮支架的聚焦文库对Shp2和Shp1 PTP活性的抑制作用。鉴定出了几种化合物，它们对Shp2的选择性抑制作用优于Shp1和蛋白酪氨酸磷酸酶1B（PTP1B），活性低至亚微摩尔级。提出了活性化合物结合的模型。
