PF-956980   Click here for help

GtoPdb Ligand ID: 11060

Synonyms: PF 956980 | PF-00956980 [3] | PF956980
PDB Ligand
Compound class: Synthetic organic
Comment: PF-956980 is an ATP-competitive, reversible pan-JAK inhibitor [1]. It is a useful commercially available JAK inhibitor tool. In addition to being an inhibitor of kinase activity, it is also reported to dose- and time-dependently reduce levels of JAK2/3 proteins (but not JAK1, as determined by Western blot) in human PBMCs, perhaps via modulating JAK2/3 synthesis [2]. This latter activity seems to be unique to PF-956980, as there are no published reports of depletion of JAK isozymes by any of the other JAK inhibitors (such as tofacitinib).
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 6
Hydrogen bond donors 1
Rotatable bonds 4
Topological polar surface area 68.36
Molecular weight 342.22
XLogP 2.32
No. Lipinski's rules broken 0
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Canonical SMILES C[C@@H]1CCN(C[C@@H]1N(c1ncnc2c1cc[nH]2)C)C(=O)N1CCCC1
Isomeric SMILES C[C@@H]1CCN(C[C@@H]1N(c1ncnc2c1cc[nH]2)C)C(=O)N1CCCC1
InChI InChI=1S/C18H26N6O/c1-13-6-10-24(18(25)23-8-3-4-9-23)11-15(13)22(2)17-14-5-7-19-16(14)20-12-21-17/h5,7,12-13,15H,3-4,6,8-11H2,1-2H3,(H,19,20,21)/t13-,15+/m1/s1
1. Changelian PS, Moshinsky D, Kuhn CF, Flanagan ME, Munchhof MJ, Harris TM, Whipple DA, Doty JL, Sun J, Kent CR et al.. (2008)
The specificity of JAK3 kinase inhibitors.
Blood, 111 (4): 2155-7. [PMID:18094329]
2. Hanan EJ, Liang J, Wang X, Blake RA, Blaquiere N, Staben ST. (2020)
Monomeric Targeted Protein Degraders.
J Med Chem, 63 (20): 11330-11361. [PMID:32352776]
3. Jones P, Storer RI, Sabnis YA, Wakenhut FM, Whitlock GA, England KS, Mukaiyama T, Dehnhardt CM, Coe JW, Kortum SW et al.. (2017)
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 (2): 767-786. [PMID:27983835]