Antibodies
Oprozomib (ONX 0912)
- 貨號 Cat. No.
- S7049
- 規格 Size
- 10mM/1mL~500mg
- 品牌 Brand
- Selleckchem
Description
Oprozomib (ONX 0912)
Catalog No.S7049
Oprozomib (ONX 0912) is an orally bioavailable inhibitor for CT-L activity of 20S proteasome β5/LMP7 with IC50 of 36 nM/82 nM.
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Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw
Biological Activity
| Description | Oprozomib (ONX 0912) is an orally bioavailable inhibitor for CT-L activity of 20S proteasome β5/LMP7 with IC50of 36 nM/82 nM. | |||||
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| Targets | 20S proteasome β5 | 20S proteasome LMP7 | ||||
| IC50 | 36 nM | 82 nM [1] | ||||
| In vitro | The anti-MM activity of Oprozomib is associated with activation of caspase-8, caspase-9, caspase-3, and PARP, as well as inhibition of migration of MM cells and angiogenesis. [2] | |||||
| In vivo | Oprozomib is demonstrated an absolute bioavailability of up to 39% in rodents and dogs. It is well tolerated with repeated oral administration at doses resulting in >80% proteasome inhibition in most tissues and elicited an antitumor response in multiple human tumor xenograft and mouse syngeneic models [1]. | |||||
| Features | ||||||
Protocol(Only for Reference)
Kinase Assay: [3]
| ELISA-based active site binding assay | Samples (lysed cells or tissue homogenates) are treated for 1 h at room temperature with the biotinylated active site probe PR-584 (5-15 μM). Samples are denatured by addition of SDS (0.9% final) and heating to 100 °C for 5 min. The denatured samples are transferred to a 96-well or 384-well filter plat, mixed with streptavidin-sepharose beads (2.5-5 μL packed beads/well), and incubated for 1 h at room temperature on a plate shaker. The beads are washed 5 times with 100-200 μL /well of ELISA buffer (PBS, 1% bovine serum albumin, 0.1% Tween-20) by vacuum filtration. The beads are incubated overnight at 4 °C on a plate shaker with the following antibodies recognizing the six catalytic subunits diluted into ELISA buffer: β5, β1, and β2 diluted 1:3000, LMP7 and LMP2 diluted 1:5000, and MECL-1 diluted 1:1000. The beads are washed 5 times with 100-200 μL /well of ELISA buffer and incubated with HRP-conjugated secondary antibody diluted 1:5000 in ELISA buffer and incubated 2 h at room temperature on a plate shaker. The beads are washed 5 times with 100-200 μL /well of ELISA buffer and developed for chemiluminsecence signal using the supersignal ELISA pico substrate following the manufacturer’s instructions. Luminescence is measured on a plate reader and converted to ng of proteasome or μg/ml of lysate by comparison with 20S proteasome or untreated cell lysate standard curves. For proteasome inhibitor studies, active site probe binding values are expressed as the percent of binding relative to DMSO treated cells. |
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Cell Assay: [2]
| Cell lines | MM.1S, MM.1R, RPMI-8226, KMS12, INA-6, OPM-2, Dox-40 |
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| Concentrations | ~1 μM |
| Incubation Time | 48 h |
| Method | MTT assay |
Animal Study: [1]
| Animal Models | Non-Hodgkin’s lymphoma cell line RL xenograft, colorectal tumor cell line CT-26 xenograft |
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| Dosages | 30 mg/kg, twice weekly on days 1 and 2 |
| Administration | p.o. |
| Solubility | 1% DMSO/30% polyethylene glycol/1% Tween 80, 30 mg/mL |
References
Clinical Trial Information( data from http://clinicaltrials.gov)
| NCT Number | Recruitment | Conditions | Sponsor /Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT01129349 | Recruiting | Advanced Solid Tumors | Onyx Pharmaceuticals|Onyx Therapeutics, Inc. | 2010-04 | Phase 1 |
| NCT01416428 | Recruiting | Multiple Myeloma|Waldenstrom Macroglobulinemia | Onyx Pharmaceuticals|Onyx Therapeutics, Inc. | 2011-09 | Phase 1|Phase 2 |
| NCT01832727 | Recruiting | Multiple Myeloma | Onyx Pharmaceuticals|Onyx Therapeutics, Inc. | 2013-05 | Phase 1|Phase 2 |
Chemical Information
| Molecular Weight (MW) | 532.61 |
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| Formula | C25H32N4O7S |
| CAS No. | 935888-69-0 |
| Storage | 3 years -20℃Powder |
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| 6 months-80℃in DMSO | |
| Syonnyms | N/A |
| Solubility (25°C) * | In vitro | DMSO | 107 mg/mL (200 mM) |
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| Water | <1 mg/mL (<1 mM) | ||
| Ethanol | <1 mg/mL (<1 mM) | ||
| In vivo | 1% DMSO/30% polyethylene glycol/1% Tween 80, | 30 mg/mL | |
| * <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. | |||
| Chemical Name | L-Serinamide, O-methyl-N-[(2-methyl-5-thiazolyl)carbonyl]-L-seryl-O-methyl-N-[(1S)-2-[(2R)-2-methyl-2-oxiranyl]-2-oxo-1-(phenylmethyl)ethyl]- |
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Preparing Stock Solutions
| Stock Solution (1ml DMSO) | 1mM | 10mM | 20mM | 30mM |
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| Mass(mg) | 0.53261 | 5.3261 | 10.6522 | 15.9783 |
