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| 10mg |
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| 25mg |
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| 50mg |
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Purity: =99.79%
RG7388 (also known as Idasanutlin; RG-7388; RO5503781) is a novel, potent and highly selective antagonist of the p53-MDM2 protein-protein interaction with potential antitumor activity. With an IC50 of 6 nM, it prevents the interaction of p53 and MDM2. Inhibiting the interaction between p53 and MDM2 in order to restore p53 activity has been viewed as a promising method for treating cancer. To create small-molecule inhibitors with desirable pharmacological profiles, the hydrophobic protein-protein interaction surface poses a significant challenge. MDM2 (mouse double minute 2; Mdm2 p53 binding protein homolog) is a tumor suppressor protein that interacts with p53. By binding to MDM2, RG7388 blocks this interaction and has an effect. When the MDM2-p53 interaction is broken, p53 is not enzymatically degraded and its transcriptional activity is reinstated, which leads to the p53-mediated induction of tumor cell apoptosis. MDM2 is a p53 pathway negative regulator that is frequently overexpressed in tumor cells. As an MDM2 antagonist, RG7388 may have anticancer properties.
| Targets |
p53-MDM2 (IC50 = 6 nM)
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| ln Vitro |
In cancer cells expressing wild-type p53, isasanutlin inhibits cell proliferation with an IC50 of 30 nM and induces dose-dependent p53 stabilization, cell cycle arrest, as well as cell apoptosis.[1]
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| ln Vivo |
With an IC50 of 30 nM, isasanutlin inhibits cell proliferation in cancer cells expressing wild-type p53 and causes dose-dependent p53 stabilization, cell cycle arrest, and cell apoptosis.[1]
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| Enzyme Assay |
The 50 mM Tris-HCl, pH 7.4, 100 mM NaCl, 1 mM DTT, and 0.02 or 0.2 mg/ml BSA buffer is used for the p53-MDM2 HTRF assay. Aliquots of small-molecule inhibitors are kept at 4°C in 96-deep-well plates as stock solutions of 10 mM DMSO. Just before testing, it is thawed and blended. A biotinylated p53 peptide and GST-MDM2 are incubated with the substance for an hour at 37°C. Following the addition of Eu-8044-streptavidin and Phycolink goat anti-GST (Type 1) allophycocyanin, an hour-long incubation at room temperature is required. Using the Envision fluorescence reader, plates are read. Data sets in duplicate or triplicate between plates are used to calculate IC50 values. Data is analyzed by XLfit4 (Microsoft) using a Sigmoidal Dose-Response Model with 4 Parameter Logistic Model and the equation Y= (A+ ((B-A)/ (1+ ((C/x)^D)))), where A and B are enzyme activity in the absence or presence of infinite inhibitor compound, respectively, C is the IC50, and D is the Hill coefficient.
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| Cell Assay |
Tetrazolium dye assay is used to assess cell proliferation. The linear regression of a plot of the concentration versus percent inhibition's logarithm yields the concentration at which cell proliferation is 50% (IC50) or 90% (IC90) inhibited.
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| References |
| Molecular Formula |
C31H29CL2F2N3O4
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|---|---|
| Molecular Weight |
616.48
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| Exact Mass |
615.15
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| Elemental Analysis |
C, 60.40; H, 4.74; Cl, 11.50; F, 6.16; N, 6.82; O, 10.38
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| CAS # |
1229705-06-9
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| Related CAS # |
Idasanutlin-d3-1;Idasanutlin (enantiomer)
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| Appearance |
Solid powder
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| SMILES |
CC(C)(C)C[C@H]1[C@]([C@H]([C@@H](N1)C(=O)NC2=C(C=C(C=C2)C(=O)O)OC)C3=C(C(=CC=C3)Cl)F)(C#N)C4=C(C=C(C=C4)Cl)F
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| InChi Key |
TVTXCJFHQKSQQM-LJQIRTBHSA-N
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| InChi Code |
InChI=1S/C31H29Cl2F2N3O4/c1-30(2,3)14-24-31(15-36,19-10-9-17(32)13-21(19)34)25(18-6-5-7-20(33)26(18)35)27(38-24)28(39)37-22-11-8-16(29(40)41)12-23(22)42-4/h5-13,24-25,27,38H,14H2,1-4H3,(H,37,39)(H,40,41)/t24-,25-,27+,31-/m0/s1
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| Chemical Name |
4-[[(2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-(2,2-dimethylpropyl)pyrrolidine-2-carbonyl]amino]-3-methoxybenzoic acid
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| Synonyms |
Idasanutlin; RG-7388; RO-5503781; RG 7388; RO5503781; RG7388; RO 5503781
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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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.06 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. Solubility in Formulation 2: 5% DMSO+40% PEG 300+5% Tween 80+ddH2O: 1.25mg/mL View More
Solubility in Formulation 3: 10 mg/mL (16.22 mM) in 0.5%HPMC 1%Tween80 (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6221 mL | 8.1106 mL | 16.2211 mL | |
| 5 mM | 0.3244 mL | 1.6221 mL | 3.2442 mL | |
| 10 mM | 0.1622 mL | 0.8111 mL | 1.6221 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 |
| NCT04029688 | Recruiting | Drug: Idasanutlin Drug: Venetoclax |
Solid Tumors Neuroblastoma |
Hoffmann-La Roche | January 27, 2020 | Phase 1 Phase 2 |
| NCT02633059 | Active Recruiting |
Drug: Dexamethasone Drug: Idasanutlin |
Loss of Chromosome 17p Recurrent Plasma Cell Myeloma |
Hoffmann-La Roche | Mayo Clinic | Phase 1 Phase 2 |
| NCT02407080 | Completed | Drug: RG7388 Drug: Pegasys |
Polycythemia Vera Essential Thrombocythemia |
John Mascarenhas | April 2015 | Phase 1 |
| NCT02828930 | Completed | Drug: Idasanutlin Drug: Placebo |
Solid Tumors | Hoffmann-La Roche | September 8, 2016 | Phase 1 |
| NCT03362723 | Completed | Drug: Idasanutlin | Solid Tumors | Hoffmann-La Roche | November 27, 2017 | Phase 1 |
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