6PMA

TRK-A IN COMPLEX WITH LIGAND

6PMA の概要

• エントリーDOI: 10.2210/pdb6pma/pdb
• 分子名称: High affinity nerve growth factor receptor, N-[2-chloro-5-(trifluoromethyl)phenyl]-2-[1-(4-methoxyphenyl)-4-oxo-1,4-dihydro-5H-pyrazolo[3,4-d]pyrimidin-5-yl]acetamide (3 entities in total)
• 機能のキーワード: trk-a kinase domain, transferase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 35906.55

構造登録者

Subramanian, G.,Brown, D.G. (登録日: 2019-07-01, 公開日: 2020-02-26, 最終更新日: 2024-11-13)

主引用文献

Subramanian, G.,Vairagoundar, R.,Bowen, S.J.,Roush, N.,Zachary, T.,Javens, C.,Williams, T.,Janssen, A.,Gonzales, A.
Synthetic inhibitor leads of human tropomyosin receptor kinase A ( h TrkA).
Rsc Med Chem, 11:370-377, 2020

PubMed Abstract: virtual screening followed by biochemical, biophysical, and cellular screening resulted in the identification of distinctly different TrkA kinase domain inhibitor scaffolds. X-ray structural analysis of representative inhibitors bound to TrkA kinase domain defined the binding mode and rationalized the mechanism of action. Preliminary assessment of the sub-type selectivity against the closest TrkB isoform, and early ADME guided the progression of select inhibitor leads in the screening cascade. The possibility of the actives sustaining to known TrkA resistance mutations assessed offers initial guidance into the required multiparametric lead optimization to arrive at a clinical candidate.

PubMed: 33479642
DOI: 10.1039/c9md00554d

実験手法

X-RAY DIFFRACTION (2.53 Å)