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Purity: ≥98%
Oprozomib (formerly known as ONX 0912 and PR 047) is a novel, potent, and orally bioavailable small molecule inhibitor that has the ability to potentially inhibit tumor growth by blocking the chymotrypsin-like (CT)-L activity of 20S proteasome β5/LMP7. The inhibitory concentration of 20S proteasome β5/LMP7 is 36 nM/82 nM. In both mouse syngeneic models and multiple human tumor xenografts, oprozomib demonstrated strong antitumor activity in vivo.
| Targets |
20S proteasome β5 (IC50 = 36 nM); 20S proteasome LMP7 (IC50 = 82 nM)
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| ln Vitro |
Oprozomib inhibits 20S chymotrypsin-like (CT-L) at an IC50 of 55 ± 19․nM.
Oprozomib inhibits human leukemia The CT-L of molt-4 cells has an IC50 of 66 nM [1]. Oprozomib (ONX 0912; 1-1000 nM; 48 hours) reduces human multiple myeloma (MM) cell lines' viability considerably[2]. The activation of caspase-8, caspase-9, caspase-3, and PARP is linked to oprozomib's anti-MM activity[2]. |
| ln Vivo |
Oprozomib (PR-047) has an absolute bioavailability of up to 39% in rodents and dogs[1], and it selectively inhibits the chymotrypsin-like (CT-L) activity of the constitutive proteasome (β5) and immunoproteasome (LMP7).[1]
Oprozomib, when taken orally at doses lower than the maximum tolerated dose (MTD), enhances antitumor activity in various animal models[1]. Oprozomib (30 mg/kg by oral gavage once daily for 5 consecutive days followed by 2 days of rest) treatment dreduces the amount of tumor in NOD.SCID.IL2Rγ-/- and C57Bl/6 mice[3]. |
| Enzyme Assay |
Probe PR-584 (5-15 μM) biotinylated active site is applied to samples (lysed cells or tissue homogenates) for 1 hour at room temperature. By adding 0.9% final SDS and heating the samples to 100 °C for five minutes, the samples are denatured. Following the denatured samples' transfer to a 96-or 384-well filter plate, streptavidin-sepharose beads (2.5–5 μL packed beads/well) are added, and the plate is shaken to incubate the mixture for one hour at room temperature. The ELISA buffer (PBS, 1% bovine serum albumin, 0.1% Tween-20) is vacuum-filtered five times through 100–200 μL/well to wash the beads. The following antibodies are used to incubate the beads overnight at 4 °C on a plate shaker. The antibodies are diluted into ELISA buffer and recognize the six catalytic subunits: β5, β1, and β2 at 1:3000, LMP7 and LMP2 at 1:5000, and MECL-1 at 1:1000. After washing the beads five times with 100–200 μL of ELISA buffer per well, they are incubated for two hours at room temperature on a plate shaker with a 1:5000 dilution of HRP-conjugated secondary antibody. The beads are developed for chemiluminescence signal using the supersignal ELISA pico substrate in accordance with the manufacturer's instructions after being washed five times with 100–200 μL of ELISA buffer per well. Via comparison with standard curves for untreated cell lysate or 20S proteasome, luminosity is measured on a plate reader and converted to ng of proteasome or μg/ml of lysate. Active site probe binding values for proteasome inhibitor investigations are reported as the percentage of binding in comparison to cells treated with DMSO.
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| Cell Assay |
Trypan blue exclusion assays showed that ONX 0912 exhibited IC50 values in 8 different HNSCC cell lines, ranging from 58.9 to 185.7 nmol/L. Treatment with ONX 0912 caused caspase-3 to be processed into active subunits and the caspase substrate PARP to be cleaved in the four HNSCC cell lines (UMSCC-1, UMSCC-22B, 1483, and UMSCC-1) that were studied.
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| Animal Protocol |
Non-Hodgkin’s lymphoma cell line RL xenograft, colorectal tumor cell line CT-26 xenograft
30 mg/kg, twice weekly on days 1 and 2 p.o. |
| References |
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| Additional Infomation |
Oprozomib has been used in trials studying the treatment of Solid Tumors, Multiple Myeloma, Waldenstrom Macroglobulinemia, Advanced Hepatocellular Carcinoma, and Advanced Non-Central Nervous System (CNS) Malignancies.
Oprozomib is an orally bioavailable proteasome inhibitor with potential antineoplastic activity. Proteasome inhibitor ONX 0912 inhibits the activity of the proteasome, thereby blocking the targeted proteolysis normally performed by the proteasome; this may result in an accumulation of unwanted or misfolded proteins. Disruption of various cell signaling pathways may follow, eventually leading to the induction of apoptosis and inhibition of tumor growth. Proteasomes are large protease complexes that degrade unneeded or damaged proteins that have been ubiquitinated. |
| Molecular Formula |
C25H32N4O7S
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| Molecular Weight |
532.61
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| Exact Mass |
532.199
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| Elemental Analysis |
C, 56.38; H, 6.06; N, 10.52; O, 21.03; S, 6.02
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| CAS # |
935888-69-0
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| Related CAS # |
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| PubChem CID |
25067547
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| Appearance |
white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
849.9±65.0 °C at 760 mmHg
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| Flash Point |
467.8±34.3 °C
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| Vapour Pressure |
0.0±3.2 mmHg at 25°C
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| Index of Refraction |
1.573
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| LogP |
2.79
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
14
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| Heavy Atom Count |
37
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| Complexity |
825
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| Defined Atom Stereocenter Count |
4
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| SMILES |
C([C@@]1(OC1)C)(=O)[C@@H](NC(=O)[C@H](COC)NC(=O)[C@H](COC)NC(C1SC(C)=NC=1)=O)CC1C=CC=CC=1
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| InChi Key |
SWZXEVABPLUDIO-WSZYKNRRSA-N
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| InChi Code |
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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| 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
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| Synonyms |
ONX 0912; ONX-0912; ONX0912; PR047; PR 047; PR-047
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.91 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (3.91 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (3.91 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8775 mL | 9.3877 mL | 18.7755 mL | |
| 5 mM | 0.3755 mL | 1.8775 mL | 3.7551 mL | |
| 10 mM | 0.1878 mL | 0.9388 mL | 1.8775 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT01129349 | Completed | Drug: Oprozomib | Solid Tumors | Amgen | April 2010 | Phase 1 |
| NCT02072863 | Completed | Drug: Oprozomib Drug: Melphalan |
Multiple Myeloma | Amgen | January 2014 | Phase 1 Phase 2 |
| NCT01832727 | Terminated | Drug: Oprozomib Drug: Dexamethasone |
Multiple Myeloma | Amgen | July 2, 2013 | Phase 1 Phase 2 |
| NCT02244112 | Terminated | Drug: Oprozomib Drug: Midazolam |
Advanced Non-Central Nervous System (CNS) Malignancies |
Amgen | August 2014 | Phase 1 |
| NCT01881789 | Terminated | Drug: Oprozomib Drug: Lenalidomide |
Multiple Myeloma | Amgen | October 28, 2013 | Phase 1 Phase 2 |
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