5TQ6

Design and Synthesis of a pan-JAK Kinase Inhibitor Clinical Candidate (PF-06263276) Suitable for Inhaled and Topical Delivery for the Treatment of Inflammatory Diseases of the Lungs and Skin

Summary for 5TQ6

• Entry DOI: 10.2210/pdb5tq6/pdb
• Related: 5TQ3 5TQ4 5TQ5 5TQ7 5TQ8
• Descriptor: Tyrosine-protein kinase JAK2, {(3R,4R)-4-methyl-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]piperidin-1-yl}(pyrrolidin-1-yl)methanone (3 entities in total)
• Functional Keywords: kinase, inflammation, jak inhibitor, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (Human)
• Cellular location: Endomembrane system ; Peripheral membrane protein : O60674
• Total number of polymer chains: 2
• Total formula weight: 72498.25

Authors

Chrencik, J.,Jones, P. (deposition date: 2016-10-23, release date: 2017-01-11, Last modification date: 2024-10-09)

Primary citation

Jones, P.,Storer, R.I.,Sabnis, Y.A.,Wakenhut, F.M.,Whitlock, G.A.,England, K.S.,Mukaiyama, T.,Dehnhardt, C.M.,Coe, J.W.,Kortum, S.W.,Chrencik, J.E.,Brown, D.G.,Jones, R.M.,Murphy, J.R.,Yeoh, T.,Morgan, P.,Kilty, I.
Design and Synthesis of a Pan-Janus Kinase Inhibitor Clinical Candidate (PF-06263276) Suitable for Inhaled and Topical Delivery for the Treatment of Inflammatory Diseases of the Lungs and Skin.
J. Med. Chem., 60:767-786, 2017

PubMed Abstract: By use of a structure-based computational method for identification of structurally novel Janus kinase (JAK) inhibitors predicted to bind beyond the ATP binding site, a potent series of indazoles was identified as selective pan-JAK inhibitors with a type 1.5 binding mode. Optimization of the series for potency and increased duration of action commensurate with inhaled or topical delivery resulted in potent pan-JAK inhibitor 2 (PF-06263276), which was advanced into clinical studies.

PubMed: 27983835
DOI: 10.1021/acs.jmedchem.6b01634

Experimental method

X-RAY DIFFRACTION (2.06 Å)