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

Summary for 5I8A

• Entry DOI: 10.2210/pdb5i8a/pdb
• Descriptor: 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)
• Functional Keywords: kinase, inhibitor, active site, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 34335.94

Authors

Su, H.P. (deposition date: 2016-02-18, release date: 2017-08-09, Last modification date: 2024-03-06)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.33 Å)