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Oprozomib Proteasome inhibitor

Name: Oprozomib
Brand: Selleck Chemicals
SKU: S7049
Availability: InStock
Rating: 5 (20 reviews)

Cat.No.S7049

Oprozomib is an orally bioavailable inhibitor for CT-L activity of 20S proteasome β5/LMP7 with IC50 of 36 nM/82 nM. Phase 1/2.

Chemical Structure

Molecular Weight: 532.61

Jump to Mechanism of Action Solubility Chemical Information, Storage & Stability Specificity

Quality Control

Batch: Purity: 99.97%

99.97

Related Targets	HDAC Caspase MMP HCV Protease Cysteine Protease DPP Tyrosinase HIV Protease Serine Protease Secretase PCSK9 Glutaminase Acyltransferase Thrombin Cathepsin B MALT PAD PREP Neprilysin SGK Aminopeptidase 3C-Like Protease PGDS GOT
Related Products	MG132 Epoxomicin (BU-4061T) Celastrol ONX-0914 (PR-957) Delanzomib VR23 Marizomib (Salinosporamide A) PI-1840 Isoginkgetin S5a/PSMD4 Antibody [L2F5] PSMD11 Antibody [L2N1] PSMB5 Antibody [F16L3] Ubiquitin (linkage-specific K27) Antibody [J11K4] S5a/PSMD4 Antibody [K9M17] RA-190 PSMB6 Antibody [P14M13] Laminin Receptor Antibody [L4P5] MG-115 KSQ-4279 (USP1-IN-1) Proteasome 20S LMP7 Antibody [N6D20]

Chemical Information, Storage & Stability

Molecular Weight	532.61	Formula	C₂₅H₃₂N₄O₇S	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	935888-69-0	--		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	ONX 0912, PR-047			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

Solubility

In vitro
Batch:

DMSO : 100 mg/mL (187.75 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	5.000mg/ml (9.39mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	0.625mg/ml (1.17mM)	Taking the 1 mL working solution as an example, add 50 μL of 12.5 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Mechanism of Action

Targets/IC₅₀/Ki	20S proteasome β5 ^[1] 36 nM 20S proteasome LMP7 ^[1] 82 nM
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]
Kinase Assay	ELISA-based active site binding assay
Kinase 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.
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].
References	[1] https://pubmed.ncbi.nlm.nih.gov/19348473/ [2] https://pubmed.ncbi.nlm.nih.gov/20805366/ [3] https://pubmed.ncbi.nlm.nih.gov/19525961/

Applications

Methods	Biomarkers	Images	PMID
Western blot	Cyclin D1 / Cyclin D2 / Cyclin E / p21(waf1/cip1) / p27(kip1) β-catenin / GRP94 / PERK / p-EIF2α / BiP / PDI / ATF4 Bcl-2 / Bcl-xL / Mcl-1 / Bik / Bim / Bax / Bak		20110419
Growth inhibition assay	Cell viability		20805366

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT01999335	Terminated	Multiple Myeloma	Amgen	July 30 2014	Phase 1
NCT01832727	Terminated	Multiple Myeloma	Amgen	July 2 2013	Phase 1\|Phase 2
NCT01416428	Terminated	Multiple Myeloma\|Waldenstrom Macroglobulinemia	Amgen	October 15 2011	Phase 1\|Phase 2

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