ONX-0914   Click here for help

GtoPdb Ligand ID: 9031

Synonyms: PR-957
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Proteolix (later Onyx Pharmaceuticals, now Amgen) developed the peptidomimetic inhibitor PR-957 (ONX-0914), which selectively inhibited the chymotrypsin-like activity of LMP7. This blocked presentation of LMP7-specific, MHC-I-restricted antigens and reduced immunoproteasome production of pro-inflammatory cytokines such as IL-6, IFN-γ, TNF-α and IL-23 [1]. Note there are at least 6 isomeric alternatives for this structure including ChEMBL entries and SureChEMBL patent mappings (see "same connectivity" links in the PubChem CID entry).
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 10
Hydrogen bond donors 3
Rotatable bonds 17
Topological polar surface area 138.6
Molecular weight 580.29
XLogP 0.69
No. Lipinski's rules broken 1
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Canonical SMILES COc1ccc(cc1)CC(C(=O)NC(C(=O)C1(C)CO1)Cc1ccccc1)NC(=O)C(NC(=O)CN1CCOCC1)C
Isomeric SMILES COc1ccc(cc1)C[C@@H](C(=O)N[C@H](C(=O)[C@@]1(C)CO1)Cc1ccccc1)NC(=O)[C@@H](NC(=O)CN1CCOCC1)C
InChI InChI=1S/C31H40N4O7/c1-21(32-27(36)19-35-13-15-41-16-14-35)29(38)34-26(18-23-9-11-24(40-3)12-10-23)30(39)33-25(28(37)31(2)20-42-31)17-22-7-5-4-6-8-22/h4-12,21,25-26H,13-20H2,1-3H3,(H,32,36)(H,33,39)(H,34,38)/t21-,25-,26-,31+/m0/s1
Bioactivity Comments
From Fig 1b in [1] the IC50 vs. LMP7 is approximately 100 nM
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
proteasome 20S subunit beta 8 Primary target of this compound Hs Inhibitor Inhibition 7.0 pIC50 - 1
pIC50 7.0 (IC50 1x10-7 M) [1]