6VNS

Crystal structure of TYK2 kinase with compound 13

Summary for 6VNS

• Entry DOI: 10.2210/pdb6vns/pdb
• Descriptor: Non-receptor tyrosine-protein kinase TYK2, (1R,2R)-2-cyano-N-[(1S,5R)-3-(5-fluoro-2-{[1-(2-hydroxyethyl)-1H-pyrazol-4-yl]amino}pyrimidin-4-yl)-3-azabicyclo[3.1.0]hexan-1-yl]cyclopropane-1-carboxamide (3 entities in total)
• Functional Keywords: kinase, transferase, transferase-inhibitor complex, transferase/inhibitor
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 36962.99

Authors

Vajdos, F.F. (deposition date: 2020-01-29, release date: 2020-04-08, Last modification date: 2023-11-15)

Primary citation

Fensome, A.,Ambler, C.M.,Arnold, E.,Banker, M.E.,Clark, J.D.,Dowty, M.E.,Efremov, I.V.,Flick, A.,Gerstenberger, B.S.,Gifford, R.S.,Gopalsamy, A.,Hegen, M.,Jussif, J.,Limburg, D.C.,Lin, T.H.,Pierce, B.S.,Sharma, R.,Trujillo, J.I.,Vajdos, F.F.,Vincent, F.,Wan, Z.K.,Xing, L.,Yang, X.,Yang, X.
Design and optimization of a series of 4-(3-azabicyclo[3.1.0]hexan-3-yl)pyrimidin-2-amines: Dual inhibitors of TYK2 and JAK1.
Bioorg.Med.Chem., 28:115481-115481, 2020

PubMed Abstract: Herein, we disclose a new series of TYK2/ JAK1 inhibitors based upon a 3.1.0 azabicyclic substituted pyrimidine scaffold. We illustrate the use of structure-based drug design for the initial design and subsequent optimization of this series of compounds. One advanced example 19 met program objectives for potency, selectivity and ADME, and demonstrated oral activity in the adjuvant-induced arthritis rat model.

PubMed: 32253095
DOI: 10.1016/j.bmc.2020.115481

Experimental method

X-RAY DIFFRACTION (2.09 Å)