oprozomib   Click here for help

GtoPdb Ligand ID: 8739

Synonyms: ONX 0912 | ONX-0912 | PR-047
Compound class: Synthetic organic
Comment: Oprozomib is an orally bioavailable derivative of carfilzomib, with similar biological action, i.e. inhibition of the chymotrypsin-like activity (a.k.a. β5 activity) of the proteasome [1-2]. This is compound 58 in [4].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 11
Hydrogen bond donors 3
Rotatable bonds 17
Topological polar surface area 176.49
Molecular weight 532.2
XLogP -1.24
No. Lipinski's rules broken 2
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Canonical SMILES COCC(C(=O)NC(C(=O)C1(C)OC1)Cc1ccccc1)NC(=O)C(NC(=O)c1cnc(s1)C)COC
Isomeric SMILES COC[C@@H](C(=O)N[C@H](C(=O)[C@]1(C)OC1)Cc1ccccc1)NC(=O)[C@@H](NC(=O)c1cnc(s1)C)COC
InChI InChI=1S/C25H32N4O7S/c1-15-26-11-20(37-15)24(33)29-19(13-35-4)23(32)28-18(12-34-3)22(31)27-17(21(30)25(2)14-36-25)10-16-8-6-5-7-9-16/h5-9,11,17-19H,10,12-14H2,1-4H3,(H,27,31)(H,28,32)(H,29,33)/t17-,18-,19-,25+/m0/s1
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Summary of Clinical Use Click here for help
Oprozomib is being evaluated in Phase 2 clinical trials in patients with multiple myeloma (MM) and advanced hepatocellular carcinoma.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Oprozomib activates the unfolded protein response (UPR), inducing ATF4-mediated autophagy in HNSCC cells and inhibits HNSCC xenograft tumor growth in vivo [3]. Oprozomib is cytotoxic against multiple myeloma in vitro and in vivo with actions including induction of apoptosis, decreased angiogenesisand associated tumour inhibition [1].