Tyrosine phosphatase SHP2 inhibitors in tumor-targeted therapies.
Tyrosine phosphatase SHP2 inhibitors in tumor-targeted therapies.
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酪氨酸磷酸酶 SHP2 抑制剂在肿瘤靶向治疗中的应用
DOI：
10.1016/j.apsb.2020.07.010
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Xiong XF
中科院分区：
文献类型：
--
作者：
Song Z;Wang M;Ge Y;Chen XP;Xu Z;Sun Y;Xiong XF
含有蛋白酪氨酸磷酸酶 2 (SHP2) 的 Src 同源物代表了多种疾病的值得注意的靶标，是癌症中众所周知的致癌磷酸酶。由于细胞渗透性低、生物利用度差，传统的针对蛋白酪氨酸磷酸催化位点的抑制剂普遍应用效果不理想。最近，已经鉴定出大量对 SHP2 具有显着抑制效力的变构抑制剂。特别是，很少有临床试验通过使用 SHP2 变构抑制剂在实体瘤方面取得重大进展。本文综述了用于肿瘤治疗的小分子SHP2抑制剂的发展和构效关系研究，旨在协助未来开发选择性更高、口服生物利用度更高、理化性质更好的SHP2抑制剂。本文综述了小分子SHP2抑制剂的发展、构效关系研究以及SHP2抑制剂在肿瘤治疗中的应用。根据每种抑制剂的化学类型、活性、选择性和共晶结构，讨论了它们的发现和开发。
Src homology containing protein tyrosine phosphatase 2 (SHP2) represents a noteworthy target for various diseases, serving as a well-known oncogenic phosphatase in cancers. As a result of the low cell permeability and poor bioavailability, the traditional inhibitors targeting the protein tyrosine phosphate catalytic sites are generally suffered from unsatisfactory applied efficacy. Recently, a particularly large number of allosteric inhibitors with striking inhibitory potency on SHP2 have been identified. In particular, few clinical trials conducted have made significant progress on solid tumors by using SHP2 allosteric inhibitors. This review summarizes the development and structure–activity relationship studies of the small-molecule SHP2 inhibitors for tumor therapies, with the purpose of assisting the future development of SHP2 inhibitors with improved selectivity, higher oral bioavailability and better physicochemical properties. This review summarized the development and structure–activity relationship studies of the small-molecule SHP2 inhibitors, as well as the application of SHP2 inhibitors for tumor therapies. The discovery and development of each type inhibitors were discussed based on their chemotypes, activity, selectivity and cocrystal structures.
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影响因子：
82.9
作者：
Dardaei L;Wang HQ;Singh M;Fordjour P;Shaw KX;Yoda S;Kerr G;Yu K;Liang J;Cao Y;Chen Y;Lawrence MS;Langenbucher A;Gainor JF;Friboulet L;Dagogo-Jack I;Myers DT;Labrot E;Ruddy D;Parks M;Lee D;DiCecca RH;Moody S;Hao H;Mohseni M;LaMarche M;Williams J;Hoffmaster K;Caponigro G;Shaw AT;Hata AN;Benes CH;Li F;Engelman JA
通讯作者：
Engelman JA
影响因子：
4.4
作者：
Chemnitz, JM;Parry, RV;Riley, JL
通讯作者：
Riley, JL
影响因子：
5.6
作者：
Halgren, Thomas A.
通讯作者：
Halgren, Thomas A.
影响因子：
7.3
作者：
Fortanet, Jorge Garcia;Chen, Christine Hiu-Tung;LaMarche, Matthew J.
通讯作者：
LaMarche, Matthew J.
BCR-ABL1诱导的血液学肿瘤需要SHP2。
影响因子：
11.4
作者：
Gu S;Sayad A;Chan G;Yang W;Lu Z;Virtanen C;Van Etten RA;Neel BG
通讯作者：
Neel BG