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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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Click here for structure editor
Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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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
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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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
InChI Key SWZXEVABPLUDIO-WSZYKNRRSA-N
References
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]