evobrutinib   

GtoPdb Ligand ID: 9752

Synonyms: A250 [WO2012170976] | M-2951 | M2951 | MSC 2364447 | MSC-2364447C | MSC2364447C
Compound class: Synthetic organic
Comment: Evobrutinib is a Bruton's tyrosine kinase Inhibitor discovered by Merck, that has clinical potential across multiple autoimmune conditions (including rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis) [1]. it is an orally active, ootent, and highly selective inhibitor with a covalent binding mode. The chemical structure is claimed as A250 in patent WO2012170976 [3].
2D Structure
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Physico-chemical Properties
Hydrogen bond acceptors 6
Hydrogen bond donors 2
Rotatable bonds 8
Topological polar surface area 93.37
Molecular weight 429.22
XLogP 4.11
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
Canonical SMILES C=CC(=O)N1CCC(CC1)CNc1ncnc(c1c1ccc(cc1)Oc1ccccc1)N
Isomeric SMILES C=CC(=O)N1CCC(CC1)CNc1ncnc(c1c1ccc(cc1)Oc1ccccc1)N
InChI InChI=1S/C25H27N5O2/c1-2-22(31)30-14-12-18(13-15-30)16-27-25-23(24(26)28-17-29-25)19-8-10-21(11-9-19)32-20-6-4-3-5-7-20/h2-11,17-18H,1,12-16H2,(H3,26,27,28,29)
InChI Key QUIWHXQETADMGN-UHFFFAOYSA-N
Bioactivity Comments
Evobrutinib exhibits high selectivity for BTK over the EGFR and other Tec family kinases. This profile suggests that evobrutinib is likely to have a reduced potential for off-target related adverse effects compared to existing less selective BTK inhibitors like ibrutinib. The improved selectivity profile and reduced propensity to cause adverse side-effects means that evobrutinib is suitable for evaluation in non-oncology indications. In contrast, the serious side-effects profile of ibrutinib precludes its evaluation in diseases other than life-threatening cancers.
Selectivity at enzymes
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
Bruton tyrosine kinase Hs Inhibitor Inhibition >7.0 pIC50 - 3
pIC50 >7.0 (IC50 <1x10-7 M) [3]
Description: Binned value derived from a time-dependent BTK enzyme assay.