6I82

Crystal structure of partially phosphorylated RET V804M tyrosine kinase domain complexed with PDD00018412

Summary for 6I82

• Entry DOI: 10.2210/pdb6i82/pdb
• Related: 6I83
• Descriptor: Proto-oncogene tyrosine-protein kinase receptor Ret, ~{N}-[3-(1,3-benzodioxol-5-yl)pyrazolo[1,5-a]pyrimidin-5-yl]-~{N}',~{N}'-dimethyl-propane-1,3-diamine, 1,2-ETHANEDIOL, ... (6 entities in total)
• Functional Keywords: inhibitor, kinase, proto-oncogene, oncoprotein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 73355.51

Authors

Burschowsky, D.,Seewooruthun, C.,Bayliss, R.,Carr, M.D.,Echalier, A.,Jordan, A.M. (deposition date: 2018-11-19, release date: 2020-03-11, Last modification date: 2024-01-24)

Primary citation

Newton, R.,Waszkowycz, B.,Seewooruthun, C.,Burschowsky, D.,Richards, M.,Hitchin, S.,Begum, H.,Watson, A.,French, E.,Hamilton, N.,Jones, S.,Lin, L.Y.,Waddell, I.,Echalier, A.,Bayliss, R.,Jordan, A.M.,Ogilvie, D.
Discovery and Optimization of wt-RET/KDR-Selective Inhibitors of RETV804MKinase.
Acs Med.Chem.Lett., 11:497-505, 2020

PubMed Abstract: A combination of focused library and virtual screening, hit expansion, and rational design has resulted in the development of a series of inhibitors of RET kinase, the anticipated drug-resistant mutant of RET kinase. These agents do not inhibit the wild type (wt) isoforms of RET or KDR and therefore offer a potential adjunct to RET inhibitors currently undergoing clinical evaluation.

PubMed: 32292556
DOI: 10.1021/acsmedchemlett.9b00615

Experimental method

X-RAY DIFFRACTION (2.05 Å)