E-viri
Recenzirano
-
LaMarche, Matthew J; Acker, Michael; Argintaru, Andreea; Bauer, Daniel; Boisclair, Julie; Chan, Homan; Chen, Christine Hiu-Tung; Chen, Ying-Nan; Chen, Zhouliang; Deng, Zhan; Dore, Michael; Dunstan, David; Fan, Jianmei; Fekkes, Peter; Firestone, Brant; Fodor, Michelle; Garcia-Fortanet, Jorge; Fortin, Pascal D; Fridrich, Cary; Giraldes, John; Glick, Meir; Grunenfelder, Denise; Hao, Huia-Xiang; Hentemann, Martin; Ho, Samuel; Jouk, Andriana; Kang, Zhao B; Karki, Rajesh; Kato, Mitsunori; Keen, Nick; Koenig, Robert; LaBonte, Laura R; Larrow, Jay; Liu, Gang; Liu, Shumei; Majumdar, Dyuti; Mathieu, Simon; Meyer, Matthew J; Mohseni, Morvarid; Ntaganda, Rukundo; Palermo, Mark; Perez, Lawrence; Pu, Minying; Ramsey, Timothy; Reilly, John; Sarver, Patrick; Sellers, William R; Sendzik, Martin; Shultz, Michael D; Slisz, Joanna; Slocum, Kelly; Smith, Troy; Spence, Stanley; Stams, Travis; Straub, Christopher; Tamez, Victoriano; Toure, Bakary-Barry; Towler, Christopher; Wang, Ping; Wang, Hongyun; Williams, Sarah L; Yang, Fan; Yu, Bing; Zhang, Ji-Hu; Zhu, Suzanne
Journal of medicinal chemistry, 11/2020, Letnik: 63, Številka: 22Journal Article
SHP2 is a nonreceptor protein tyrosine phosphatase encoded by the PTPN11 gene and is involved in cell growth and differentiation via the MAPK signaling pathway. SHP2 also plays an important role in the programed cell death pathway (PD-1/PD-L1). As an oncoprotein as well as a potential immunomodulator, controlling SHP2 activity is of high therapeutic interest. As part of our comprehensive program targeting SHP2, we identified multiple allosteric binding modes of inhibition and optimized numerous chemical scaffolds in parallel. In this drug annotation report, we detail the identification and optimization of the pyrazine class of allosteric SHP2 inhibitors. Structure and property based drug design enabled the identification of protein–ligand interactions, potent cellular inhibition, control of physicochemical, pharmaceutical and selectivity properties, and potent in vivo antitumor activity. These studies culminated in the discovery of TNO155, (3S,4S)-8-(6-amino-5-((2-amino-3-chloropyridin-4-yl)thio)pyrazin-2-yl)-3-methyl-2-oxa-8-azaspiro4.5decan-4-amine (1), a highly potent, selective, orally efficacious, and first-in-class SHP2 inhibitor currently in clinical trials for cancer.
Avtor
![loading ... loading ...](themes/default/img/ajax-loading.gif)
Vnos na polico
Trajna povezava
- URL:
Faktor vpliva
Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Baze podatkov, v katerih je revija indeksirana
Ime baze podatkov | Področje | Leto |
---|
Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
---|
Vir: Osebne bibliografije
in: SICRIS
To gradivo vam je dostopno v celotnem besedilu. Če kljub temu želite naročiti gradivo, kliknite gumb Nadaljuj.