6w8l

From Proteopedia

Crystal structure of JAK1 kinase with compound 10

Structural highlights

6w8l is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.11Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

JAK1_HUMAN Tyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway. Kinase partner for the interleukin (IL)-2 receptor.

Publication Abstract from PubMed

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.

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.,Fensome A, Ambler CM, Arnold E, Banker ME, Clark JD, Dowty ME, Efremov IV, Flick A, Gerstenberger BS, Gifford RS, Gopalsamy A, Hegen M, Jussif J, Limburg DC, Lin TH, Pierce BS, Sharma R, Trujillo JI, Vajdos FF, Vincent F, Wan ZK, Xing L, Yang X, Yang X Bioorg Med Chem. 2020 May 15;28(10):115481. doi: 10.1016/j.bmc.2020.115481. Epub , 2020 Mar 31. PMID:32253095^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Fensome A, Ambler CM, Arnold E, Banker ME, Clark JD, Dowty ME, Efremov IV, Flick A, Gerstenberger BS, Gifford RS, Gopalsamy A, Hegen M, Jussif J, Limburg DC, Lin TH, Pierce BS, Sharma R, Trujillo JI, Vajdos FF, Vincent F, Wan ZK, 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. 2020 May 15;28(10):115481. doi: 10.1016/j.bmc.2020.115481. Epub , 2020 Mar 31. PMID:32253095 doi:http://dx.doi.org/10.1016/j.bmc.2020.115481