5I8A

TrkA with (6~{R})-3-methylsulfanyl-6-phenyl-1-(1~{H}-pyrazol-3-yl)-6,7-dihydro-5~{H}-thieno[3,4-c]pyridin-4-one

5I8A の概要

• エントリーDOI: 10.2210/pdb5i8a/pdb
• 分子名称: High affinity nerve growth factor receptor, (6R)-3-(methylsulfanyl)-6-phenyl-1-(1H-pyrazol-3-yl)-6,7-dihydrothieno[3,4-c]pyridin-4(5H)-one, CHLORIDE ION, ... (5 entities in total)
• 機能のキーワード: kinase, inhibitor, active site, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 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: 34335.94

構造登録者

Su, H.P. (登録日: 2016-02-18, 公開日: 2017-08-09, 最終更新日: 2024-03-06)

主引用文献

Greshock, T.J.,Sanders, J.M.,Drolet, R.E.,Rajapakse, H.A.,Chang, R.K.,Kim, B.,Rada, V.L.,Tiscia, H.E.,Su, H.,Lai, M.T.,Sur, S.M.,Sanchez, R.I.,Bilodeau, M.T.,Renger, J.J.,Kern, J.T.,McCauley, J.A.
Potent, selective and orally bioavailable leucine-rich repeat kinase 2 (LRRK2) inhibitors.
Bioorg. Med. Chem. Lett., 26:2631-2635, 2016

PubMed Abstract: Familial Parkinson's disease cases have recently been associated with the leucine rich repeat kinase 2 (LRRK2) gene. It has been hypothesized that inhibition of the LRRK2 protein may have the potential to alter disease pathogenesis. A dihydrobenzothiophene series of potent, selective, orally bioavailable LRRK2 inhibitors were identified from a high-throughput screen of the internal Merck sample collection. Initial SAR studies around the core established the series as a tractable small molecule lead series of LRRK2 inhibitors for potential treatment of Parkinson's disease. It was also found that incorporation of a lactam into the core drastically improved the CNS and DMPK properties of these small molecules.

PubMed: 27106707
DOI: 10.1016/j.bmcl.2016.04.021

実験手法

X-RAY DIFFRACTION (2.33 Å)