Compound 9 [doi:10.26434/chemrxiv.7072592.v1]   Click here for help

GtoPdb Ligand ID: 10083

Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: The compound (from a pre-print) is selective KDM5 covalent inhibitor designed to target cysteine residues only present in the KDM5 sub-family [1]. Target engagement and ChIP-seq analysis showed that compound 7 inhibited KDM5B in cells and induced a global increase of the H3K4me3 mark at transcriptional start sites. KDM5B is thus involved in the epigenetic regulatory pathway of immune response and potential targets for antipathogen and anticancer immunotherapy.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 5
Hydrogen bond donors 2
Rotatable bonds 8
Topological polar surface area 112.28
Molecular weight 391.16
XLogP 3.69
No. Lipinski's rules broken 0
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Canonical SMILES C=CC(=O)NCCOc1ccc(cc1)c1[nH]c2c(C#N)cnn2c(=O)c1C(C)C
Isomeric SMILES C=CC(=O)NCCOc1ccc(cc1)c1[nH]c2c(C#N)cnn2c(=O)c1C(C)C
InChI InChI=1S/C21H21N5O3/c1-4-17(27)23-9-10-29-16-7-5-14(6-8-16)19-18(13(2)3)21(28)26-20(25-19)15(11-22)12-24-26/h4-8,12-13,25H,1,9-10H2,2-3H3,(H,23,27)
1. Vazquez-Rodriguez S, Wright M, Rogers CM, Cribbs AP, Velupillai S, Philpott M, Lee H, Dunford JE, Huber KVM, Robers MB et al.. (2019)
Design, Synthesis and Characterization of Covalent KDM5 Inhibitors.
Angew Chem Int Ed Engl, 58 (2): 515-519. DOI: 10.26434/chemrxiv.7072592.v1 [PMID:30431220]
2. Wu L, Cao J, Cai WL, Lang SM, Horton JR, Jansen DJ, Liu ZZ, Chen JF, Zhang M, Mott BT et al.. (2018)
KDM5 histone demethylases repress immune response via suppression of STING.
PLoS Biol, 16 (8): e2006134. [PMID:30080846]