8U7X
Crystal structure of non-receptor protein tyrosine phosphatase SHP2 in complex with inhibitor compound 24
Summary for 8U7X
| Entry DOI | 10.2210/pdb8u7x/pdb |
| Descriptor | Tyrosine-protein phosphatase non-receptor type 11, (3S,4S)-8-{6-[(2-amino-3-chloropyridin-4-yl)sulfanyl]pyrido[2,3-b]pyrazin-2-yl}-3-methyl-2-oxa-8-azaspiro[4.5]decan-4-amine (3 entities in total) |
| Functional Keywords | phosphatase, inhibitor, shp2, hydrolase, hydrolase-inhibitor complex, hydrolase/inhibitor |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 2 |
| Total formula weight | 125095.91 |
| Authors | |
| Primary citation | Elsayed, M.S.A.,Blake, J.F.,Boys, M.L.,Brown, E.,Chapsal, B.D.,Chicarelli, M.J.,Cook, A.W.,Fell, J.B.,Fischer, J.P.,Hanson, L.,Lemieux, C.,Martinson, M.C.,McCown, J.,McNulty, O.T.,Mejia, M.J.,Neitzel, N.A.,Otten, J.N.,Rodriguez, M.E.,Wilcox, D.,Wong, C.E.,Zhou, Y.,Hinklin, R.J. Discovery of 5-Azaquinoxaline Derivatives as Potent and Orally Bioavailable Allosteric SHP2 Inhibitors. Acs Med.Chem.Lett., 14:1673-1681, 2023 Cited by PubMed Abstract: SHP2 has emerged as an important target for oncology small-molecule drug discovery. As a nonreceptor tyrosine phosphatase within the MAPK pathway, it has been shown to control cell growth, differentiation, and oncogenic transformation. We used structure-based design to find a novel class of potent and orally bioavailable SHP2 inhibitors. Our efforts led to the discovery of the 5-azaquinoxaline as a new core for developing this class of compounds. Optimization of the potency and properties of this scaffold generated compound , that exhibited potent SHP2 inhibition and showed excellent efficacy and pharmacokinetic profile. PubMed: 38116446DOI: 10.1021/acsmedchemlett.3c00310 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.06 Å) |
Structure validation
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