7KHJ

Crystal structure of KIT kinase domain with a small molecule inhibitor, PLX8512 in the DFG-in state

Summary for 7KHJ

• Entry DOI: 10.2210/pdb7khj/pdb
• Related: 7KHG
• Descriptor: Mast/stem cell growth factor receptor Kit, 2-phenyl-5-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine (3 entities in total)
• Functional Keywords: transferase, tyrosine-protein kinase, atp-binding, kinase-kinase inhibitor complex, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 76572.88

Authors

Zhang, Y. (deposition date: 2020-10-21, release date: 2021-07-07, Last modification date: 2023-10-18)

Primary citation

Wagner, A.J.,Severson, P.L.,Shields, A.F.,Patnaik, A.,Chugh, R.,Tinoco, G.,Wu, G.,Nespi, M.,Lin, J.,Zhang, Y.,Ewing, T.,Habets, G.,Burton, E.A.,Matusow, B.,Tsai, J.,Tsang, G.,Shellooe, R.,Carias, H.,Chan, K.,Rezaei, H.,Sanftner, L.,Marimuthu, A.,Spevak, W.,Ibrahim, P.N.,Inokuchi, K.,Alcantar, O.,Michelson, G.,Tsiatis, A.C.,Zhang, C.,Bollag, G.,Trent, J.C.,Tap, W.D.
Association of Combination of Conformation-Specific KIT Inhibitors With Clinical Benefit in Patients With Refractory Gastrointestinal Stromal Tumors: A Phase 1b/2a Nonrandomized Clinical Trial.
Jama Oncol, 7:1343-1350, 2021

PubMed Abstract: Many cancer subtypes, including KIT-mutant gastrointestinal stromal tumors (GISTs), are driven by activating mutations in tyrosine kinases and may initially respond to kinase inhibitors but frequently relapse owing to outgrowth of heterogeneous subclones with resistance mutations. KIT inhibitors commonly used to treat GIST (eg, imatinib and sunitinib) are inactive-state (type II) inhibitors.

PubMed: 34236401
DOI: 10.1001/jamaoncol.2021.2086

Experimental method

X-RAY DIFFRACTION (2.8 Å)