Oprozomib (ONX-0912)
Oprozomib (ONX-0912, CAS 935888-69-0) is an orally bioavailable small-molecule inhibitor of the proteasome, structurally related to carfilzomib. It targets predominantly the chymotrypsin-like proteolytic activity of the proteasome, inducing apoptosis and growth inhibition in multiple myeloma (MM) cell lines, including those resistant to bortezomib. In preclinical models, oprozomib activates pro-apoptotic pathways involving caspases-3, -8, -9, as well as PARP cleavage, suppresses angiogenesis and tumor cell migration, thereby reducing tumor progression and prolonging survival. Its biological activity positions oprozomib as a promising compound for MM research.
References:
1. Dharminder Chauhan, Ajita V. Singh, Monette Aujay, Christopher J. Kirk, Madhavi Bandi, Bryan Ciccarelli, Noopur Raje, Paul Richardson, and Kenneth C. Anderson. A novel oraaly active proteasome inhibitor ONX 0912 triggers in vitro and in vivo cytotoxicity in multiple myeloma. Blood 2010; 116(23): 4906-4915
- 1. T. Ukmar-Godec, P. Fang, et al. "Proteasomal degradation of the intrinsically disordered protein tau at single-residue resolution." Sci Adv. 2020 Jul 22;6(30):eaba3916. PMID:32832664
- 2. Felix Lambrecht. "Computational methods for the structure determination of highly dynamic molecular machines by cryo-EM." Georg-August-Universit?t G?ttingen. 2019.
- 3. McCourt JL, Talsness DM, et al. "Mouse models of two missense mutations in actin-binding domain 1 of dystrophin associated with Duchenne or Becker muscular dystrophy." Hum Mol Genet. 2018 Feb 1;27(3):451-462. PMID:29194514
- 4. Haselbach D, Schrader J, et al. "Long-range allosteric regulation of the human 26S proteasome by 20S proteasome-targeting cancer drugs." Nat Commun. 2017 May 25;8:15578. PMID:28541292
- 5. Schrader J, Henneberg F, et al. "The inhibition mechanism of human 20S proteasomes enables next-generation inhibitor design." Science. 2016 Aug 5;353(6299):594-8. PMID:27493187
- 6. Vandewynckel YP, Coucke C, et al. "Next-generation proteasome inhibitor oprozomib synergizes with modulators of the unfolded protein response to suppress hepatocellular carcinoma."Oncotarget. 2016 Jun 7;7(23):34988-5000. PMID:27167000
| Physical Appearance | A solid |
| Storage | Desiccate at -20°C |
| M.Wt | 532.61 |
| Cas No. | 935888-69-0 |
| Formula | C25H32N4O7S |
| Synonyms | ONX-0912,ONX0912,ONX 0912,PR 047,Oprozomib |
| Solubility | ≥26.6 mg/mL in DMSO; insoluble in H2O; ≥2.77 mg/mL in EtOH with gentle warming and ultrasonic |
| Chemical Name | N-[(2S)-3-methoxy-1-[[(2S)-3-methoxy-1-[[(2S)-1-[(2R)-2-methyloxiran-2-yl]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]-2-methyl-1,3-thiazole-5-carboxamide |
| SDF | Download SDF |
| Canonical SMILES | CC1=NC=C(S1)C(=O)NC(COC)C(=O)NC(COC)C(=O)NC(CC2=CC=CC=C2)C(=O)C3(CO3)C |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment: | |
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Cell lines |
The human HNSCC cell lines UMSCC-22A, UMSCC-22B, 1483, UMSCC-1, and Cal33. |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
48 h; IC50 values ranging from 58.9 to185.7 nmol/L in 8 different HNSCC cell lines. |
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Applications |
In trypan blue exclusion assays, ONX 0912 exhibited IC50 values ranging from 58.9 to185.7 nmol/L in 8 different HNSCC cell lines. In the 4 HNSCC cell lines (UMSCC-1, UMSCC-22B, 1483, and UMSCC-1) examined, treatment ONX 0912 resulted in processing of caspase-3 to active subunits and cleavage of the caspase substrate PARP. |
| Animal experiment: | |
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Animal models |
Athymic nude mice |
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Dosage form |
30 mg/kg; Oral taken. |
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Applications |
Using nude mice harboring HNSCC xenograft tumors, oral administration of 30 mg/kg ONX 0912 effectively inhibited CT-L activity in normal and HNSCC tumor tissues. Treatments (10 mg/kg and 30 mg/kg) were administered via oral gavage once a day on 2 consecutive days and repeated weekly for 2 weeks. Treatment with 10 mg/kg ONX 0912 did not have a significant effect on tumor growth, relative to treatment with vehicle alone. In contrast, highly significant inhibition of HNSCC tumor growth was seen with 30 mg/kg ONX 0912 (P = 0.003). These results show that consecutive-day treatment with orally administered ONX 0912, using a dose that has previously been shown to be well tolerated, leads to inhibition of HNSCC tumor growth. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Zang Y, Thomas S M, Chan E T, et al. 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[J]. Clinical Cancer Research, 2012, 18(20): 5639-5649. |
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| Description | Oprozomib (ONX 0912) is an orally bioavailable inhibitor for CT-L activity of 20S proteasome β5 and LMP7 with IC50 values of 36 nM and 82 nM, respectively. | |||||
| Targets | 20S proteasome β5 | 20S proteasome LMP7 | ||||
| IC50 | 36 nM | 82 nM | ||||
Quality Control & MSDS
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