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| Targets |
PR-924 targets the immunoproteasome subunit LMP7 (β5i), which is a component of the immunoproteasome that is predominantly expressed in immune cells and is involved in the processing of antigens for MHC class I presentation. By selectively inhibiting LMP7, PR-924 modulates the immunoproteasome's proteolytic activity, leading to the accumulation of ubiquitinated proteins and induction of apoptosis in multiple myeloma cells.
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| ln Vitro |
Viability is inhibited in MM cell lines in a time- and dose-dependent manner (IC 50 range for PR-924 (1-20 μM; 24-72 hours; MM.1S, MM.1R, RPMI-8226, KMS12, LR-5, DOX40, INA-6, OPM1, and OPM2 cells) treatment significantly reduced
In vitro, PR-924 is a selective inhibitor of the immunoproteasome subunit LMP7 with an IC50 of 22 nM. It covalently modifies the N-terminal threonine active site of the proteasome. The compound inhibits growth and triggers apoptosis in multiple myeloma (MM) cells and has antitumor activities. |
| ln Vivo |
In human plasmacytoma xenografts, PR-924 (6 mg/kg; i.v.; twice weekly; for 21 days; CB-17 SCID mice) therapy significantly reduces tumor growth [1]. In the SCID-hu model, PR-924 therapy dramatically lowered shIL-6R levels. PR-924 treatment can increase the longevity of tumor-bearing animals [1].
In vivo activity data for PR-924 are limited in the available literature. As a selective immunoproteasome inhibitor, it has potential applications in the treatment of multiple myeloma and other hematologic malignancies. Its antitumor activities have been demonstrated in preclinical models, but further in vivo studies are needed to fully characterize its efficacy and safety. |
| Enzyme Assay |
In vitro enzyme inhibition assays for PR-924 are performed using purified LMP7 (β5i) or immunoproteasome preparations. The enzyme is incubated with a fluorogenic peptide substrate in the presence of increasing concentrations of the compound. The decrease in substrate cleavage is measured fluorometrically, and the IC50 (22 nM) is calculated from the inhibition curve.
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: MM.1S, MM.1R, RPMI-8226, KMS12, LR-5, DOX40, INA-6, OPM1 and OPM2 Cell Tested Concentrations: 1-20 μM Incubation Duration: 24 hrs (hours), 48 Hourly and 72 hour Experimental Results: Dramatically diminished viability of all MM cell lines in a time- and dose-dependent manner (IC 50 range for Cell Types: 3-7 μM for 48 hrs (hours)). Apoptosis analysis[1] Cell Types: MM.1S and MM.1R Cell Tested Concentrations: 3 μM Incubation Duration: 48 hrs (hours) Experimental Results: A significant increase in the annexin V+/PI-apoptotic cell population was triggered. Western Blot Analysis [1] Cell Types: MM.1S and MM.1R Cell Tested Concentrations: 3 μM Incubation Duration: 48 hrs (hours) Experimental Results: Triggers the activation of caspase-3, caspase-8 and caspase-9, and Dramatically downregulates the expression of Bcl- 2 egg whites. In vitro cellular assays for PR-924 are performed using multiple myeloma cell lines. Cells are treated with the compound, and cell viability is assessed using MTT or CellTiter-Glo assays. Apoptosis is evaluated by measuring caspase activity, annexin V staining, or PARP cleavage. Proteasome activity in cell lysates is measured using fluorogenic substrates to confirm target engagement. |
| Animal Protocol |
Animal/Disease Models: CB-17 SCID (severe combined immunodeficient) mouse injected with MM.1S cells [1]
Doses: 6 mg/kg Route of Administration: intravenous (iv) (iv)injection; twice weekly; for 21 days Experimental Results: Inhibition of human plasmacytoma xenografts of tumor growth. In vivo animal experiments for PR-924 are conducted in mouse xenograft models of multiple myeloma. A typical protocol involves administration of the compound via intraperitoneal or intravenous routes, followed by measurement of tumor volume, assessment of apoptosis markers in tumor tissues, and monitoring of body weight and general health to evaluate toxicity. |
| ADME/Pharmacokinetics |
The pharmacokinetic properties of PR-924 have been characterized in preclinical studies. The compound has a molecular weight of 618.72, molecular formula C37H38N4O5, and a purity of 98.87%. Further PK details, including half-life, bioavailability, and tissue distribution, are available from the manufacturer's data sheets.
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| Toxicity/Toxicokinetics |
The toxicity profile of PR-924 has been evaluated in preclinical studies. As a selective immunoproteasome inhibitor, its safety profile is characterized by its effects on immune function and potential for off-target proteasome inhibition. Specific toxicity data, including organ-specific effects and dose-limiting toxicities, are typically assessed in standard toxicology studies to support its development as a therapeutic agent.
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| References |
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| Additional Infomation |
PR-924 is a selective, irreversible inhibitor of the immunoproteasome subunit LMP7 (β5i) with an IC50 of 22 nM. It is a tripeptide epoxyketone that covalently modifies the N-terminal threonine active site of the proteasome. PR-924 has antitumor activities and is being studied for the treatment of multiple myeloma. This product is for research use only.
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| Molecular Formula |
C37H38N4O5
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| Molecular Weight |
618.73
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| Exact Mass |
618.284
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| CAS # |
1416709-79-9
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| Related CAS # |
(R)-PR-924
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| PubChem CID |
92135659
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| Appearance |
Off-white to light yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
969.0±65.0 °C at 760 mmHg
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| Flash Point |
539.8±34.3 °C
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| Vapour Pressure |
0.0±0.3 mmHg at 25°C
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| Index of Refraction |
1.648
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| LogP |
6.17
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
46
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| Complexity |
1200
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| Defined Atom Stereocenter Count |
4
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| SMILES |
CC1=C(CC2=CC=CC=C12)C(=O)N[C@H](C)C(=O)N[C@@H](CC3=CNC4=CC=CC=C43)C(=O)N[C@@H](CC5=CC=CC=C5)C(=O)[C@]6(CO6)C
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| InChi Key |
ADBUEVSHEJICCM-LZNHGOJSSA-N
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| InChi Code |
InChI=1S/C37H38N4O5/c1-22-27-14-8-7-13-25(27)18-29(22)35(44)39-23(2)34(43)41-32(19-26-20-38-30-16-10-9-15-28(26)30)36(45)40-31(33(42)37(3)21-46-37)17-24-11-5-4-6-12-24/h4-16,20,23,31-32,38H,17-19,21H2,1-3H3,(H,39,44)(H,40,45)(H,41,43)/t23-,31+,32+,37-/m1/s1
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| Chemical Name |
N-[(2R)-1-[[(2S)-3-(1H-indol-3-yl)-1-[[(2S)-1-[(2R)-2-methyloxiran-2-yl]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]-3-methyl-1H-indene-2-carboxamide
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| Synonyms |
PR924; PR-924; PR-924
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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 |
| 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) |
DMSO : ~50 mg/mL (~80.81 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.04 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 25.0 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: ≥ 2.5 mg/mL (4.04 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6162 mL | 8.0811 mL | 16.1621 mL | |
| 5 mM | 0.3232 mL | 1.6162 mL | 3.2324 mL | |
| 10 mM | 0.1616 mL | 0.8081 mL | 1.6162 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.
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