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| Targets |
RA375 targets RPN13 (ADRM1), a regulatory subunit of the 26S proteasome. RPN13 is involved in the recognition and deubiquitination of ubiquitinated proteins targeted for degradation. By inhibiting RPN13, RA375 disrupts proteasome function, leading to the accumulation of ubiquitinated proteins, activation of UPR signaling, ROS production, and apoptosis in cancer cells.
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| ln Vitro |
RA375 demonstrates potent in vitro activity against cancer cell lines. It activates UPR signaling and generates ROS in cancer cells. The compound's anti-tumor activity is ten-fold higher than that of RA190. These activities make RA375 a valuable tool for studying proteasome inhibition and cancer cell death pathways.
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| ln Vivo |
In mice, RA375 (10 mg/kg, ip) decreases the burden of ovarian tumors via inhibiting proteasome function[1].
In vivo activity of RA375 has been demonstrated in animal models. An animal protocol reports that RA375 (10 mg/kg, intraperitoneal) inhibits proteasome activity in vivo. The compound's potent anti-tumor activity suggests potential for efficacy in tumor-bearing mouse models. Further in vivo studies are needed to fully characterize its antitumor efficacy and safety profile. |
| Enzyme Assay |
In vitro enzyme assays for RA375 involve measuring its inhibition of RPN13 function or proteasome activity. Proteasome activity can be assessed using fluorogenic peptide substrates that are cleaved by the proteasome. Inhibition of RPN13-mediated deubiquitination can be measured using ubiquitin-AMC substrates. IC50 values can be determined from dose-response curves.
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| Cell Assay |
In vitro cellular assays for RA375 involve treating cancer cell lines with varying concentrations of the compound and measuring cell viability using MTT or other assays. UPR signaling activation is assessed by measuring markers such as CHOP or BiP. ROS production is measured using fluorescent probes such as DCFH-DA. Apoptosis is evaluated by Annexin V staining or caspase activity assays.
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| Animal Protocol |
Animal/Disease Models: RA375 (10 mg/kg, ip) inhibits proteasome function and reduces ovarian tumor burden in mice[1].
Doses: 10 mg/kg. Route of Administration: IP for a 5 days on, 2 days off cycle for two weeks. Experimental Results: diminished ovarian tumor burden in mice. Animal/Disease Models: Female balb/c (Bagg ALBino) mouse:[1]. Doses: 5, 10, 20, 40, 60, 100 mg/kg (Pharmacological Analysis). Route of Administration: IP single dose. Experimental Results: The dose of 40 mg/kg on alternate days for two weeks produced no observable toxicities or weight loss. In vivo animal experiments for RA375 involve administering the compound (e.g., 10 mg/kg, intraperitoneal) to tumor-bearing mouse models. Efficacy is evaluated by measuring tumor growth inhibition, survival rates, and biomarker changes such as UPR activation and apoptosis markers. The compound's pharmacokinetic properties and tissue distribution are also assessed. |
| ADME/Pharmacokinetics |
Pharmacokinetic data for RA375 are limited. The compound is soluble in DMSO. An animal protocol indicates intraperitoneal administration at 10 mg/kg. Its absorption, distribution, metabolism, and excretion properties have not been fully characterized. Further pharmacokinetic studies are needed to determine its bioavailability and half-life.
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| Toxicity/Toxicokinetics |
Toxicological data for RA375 are limited. As a potent proteasome inhibitor, the compound may have potential for off-target effects at higher concentrations. The compound is intended for research use only and is not for human therapeutic application. Standard laboratory safety precautions should be followed when handling this compound.
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| References | |
| Additional Infomation |
RA375 (CAS#: 2649154-57-2) has the molecular formula C30H25ClN4O7 and a molecular weight of 589.00. The compound is a RPN13 inhibitor that activates UPR signaling, generates ROS, and induces apoptosis. It exhibits ten-fold greater activity than RA190. Purity is ≥98%.
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| Molecular Formula |
C30H25CLN4O7
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|---|---|
| Molecular Weight |
588.995106458664
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| Exact Mass |
588.141
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| CAS # |
2649154-57-2
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| PubChem CID |
146681207
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
4.7
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
42
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| Complexity |
1020
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C\1N(C/C(=C\C2=CC=C(C=C2)[N+](=O)[O-])/C(=O)/C1=C/C3=CC=C(C=C3)[N+](=O)[O-])C(=O)[C@@H](NC(=O)CCl)CC4=CC=CC=C4
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| InChi Key |
REFAVUFYPFWJGH-SWAPHQFDSA-N
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| InChi Code |
InChI=1S/C30H25ClN4O7/c31-17-28(36)32-27(16-20-4-2-1-3-5-20)30(38)33-18-23(14-21-6-10-25(11-7-21)34(39)40)29(37)24(19-33)15-22-8-12-26(13-9-22)35(41)42/h1-15,27H,16-19H2,(H,32,36)/b23-14+,24-15+/t27-/m0/s1
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| Chemical Name |
N-[(2S)-1-[(3E,5E)-3,5-bis[(4-nitrophenyl)methylidene]-4-oxopiperidin-1-yl]-1-oxo-3-phenylpropan-2-yl]-2-chloroacetamide
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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 : 100 mg/mL (169.78 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6978 mL | 8.4890 mL | 16.9779 mL | |
| 5 mM | 0.3396 mL | 1.6978 mL | 3.3956 mL | |
| 10 mM | 0.1698 mL | 0.8489 mL | 1.6978 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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