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
1. Chauhan D, Singh AV, Aujay M, Kirk CJ, Bandi M, Ciccarelli B, Raje N, Richardson P, Anderson KC. (2010)
A novel orally active proteasome inhibitor ONX 0912 triggers in vitro and in vivo cytotoxicity in multiple myeloma.
Blood, 116 (23): 4906-15. [PMID:20805366]
2. Kale AJ, Moore BS. (2012)
Molecular mechanisms of acquired proteasome inhibitor resistance.
J Med Chem, 55 (23): 10317-27. [PMID:22978849]
3. Zang Y, Thomas SM, Chan ET, Kirk CJ, Freilino ML, DeLancey HM, Grandis JR, Li C, Johnson DE. (2012)
Carfilzomib and ONX 0912 inhibit cell survival and tumor growth of head and neck cancer and their activities are enhanced by suppression of Mcl-1 or autophagy.
Clin Cancer Res, 18 (20): 5639-49. [PMID:22929803]
4. Zhou HJ, Aujay MA, Bennett MK, Dajee M, Demo SD, Fang Y, Ho MN, Jiang J, Kirk CJ, Laidig GJ et al.. (2009)
Design and synthesis of an orally bioavailable and selective peptide epoxyketone proteasome inhibitor (PR-047).
J Med Chem, 52 (9): 3028-38. [PMID:19348473]