| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| Targets |
(3S,5S,6R)-Navtemadlin targets MDM2 (murine double minute 2), a negative regulator of the tumor suppressor protein p53. MDM2 binds to p53 and promotes its degradation, thereby inhibiting p53-mediated tumor suppression. By binding to MDM2, the compound disrupts the MDM2-p53 interaction, leading to the stabilization and activation of p53. Activated p53 induces the transcription of target genes involved in cell cycle arrest, apoptosis, and DNA repair. This mechanism makes MDM2 inhibitors promising anticancer agents for tumors with wild-type p53.
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| ln Vitro |
In vitro studies have demonstrated that (3S,5S,6R)-Navtemadlin potently inhibits MDM2 and activates the p53 pathway. The compound binds to MDM2 with high affinity, disrupting the MDM2-p53 interaction. In cancer cell lines with wild-type p53, treatment with the compound leads to p53 stabilization, activation of p53 target genes, and induction of apoptosis. The compound's antiproliferative activity has been evaluated in various cancer cell lines. These in vitro findings support its potential as an anticancer agent for tumors with wild-type p53.
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| ln Vivo |
In vivo studies of (3S,5S,6R)-Navtemadlin have demonstrated antitumor activity in animal models of cancer. The compound's ability to activate p53 and induce apoptosis in tumor tissues has been evaluated. Tumor growth inhibition has been observed in xenograft models. The compound's pharmacokinetic and pharmacodynamic properties have been characterized in preclinical studies. Further research is needed to fully characterize its in vivo efficacy and safety profile. The compound is intended for research use only and is not for human therapeutic use.
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| Enzyme Assay |
In vitro enzyme and receptor binding assays for (3S,5S,6R)-Navtemadlin typically involve testing its binding affinity to MDM2. Binding affinity is measured using surface plasmon resonance, isothermal titration calorimetry, or fluorescence polarization assays. The compound's ability to disrupt the MDM2-p53 interaction is assessed using ELISA or co-immunoprecipitation assays. IC50 values are determined from dose-response curves. Selectivity assays are performed against related proteins to assess specificity. All assays are performed with appropriate controls and standardized protocols.
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| Cell Assay |
In vitro cell-based assays for (3S,5S,6R)-Navtemadlin involve culturing cancer cell lines with wild-type p53 to evaluate its antiproliferative and apoptotic effects. Cells are treated with varying concentrations of the compound for specified durations (24-72 hours). Cell viability is assessed using MTT, CCK-8, or similar colorimetric assays. p53 stabilization and activation are measured by Western blotting for p53 and its target genes (e.g., p21, PUMA, Bax). Apoptosis is quantified using flow cytometry with Annexin V/PI staining or via caspase activity measurements. All experiments are performed in triplicate with appropriate controls.
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| Animal Protocol |
In vivo animal experiments for (3S,5S,6R)-Navtemadlin utilize xenograft models of cancer. Tumor-bearing mice are treated with the compound orally or intraperitoneally. Tumor growth is monitored by caliper measurements. Parameters assessed include tumor volume, tumor weight, body weight, survival, and general health. At study termination, tumors are collected for histopathological examination and biomarker analysis (p53, p21, apoptosis markers). Control groups receiving vehicle alone are included for comparison. All procedures comply with institutional animal care and use committee guidelines.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of (3S,5S,6R)-Navtemadlin reflect its nature as a small molecule MDM2 inhibitor. It has a molecular weight consistent with its structure. As a small molecule, it is expected to be absorbed through the gastrointestinal tract and distributed throughout the body. The compound is metabolized through standard xenobiotic pathways in the liver. Complete pharmacokinetic profiling including half-life, clearance, volume of distribution, and bioavailability would require further systematic studies using appropriate analytical methods such as high-performance liquid chromatography-mass spectrometry.
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| Toxicity/Toxicokinetics |
The toxicity profile of (3S,5S,6R)-Navtemadlin has been evaluated in preclinical studies. As an MDM2 inhibitor that activates p53, it may cause on-target toxicity in normal tissues that express wild-type p53. Potential toxicities include gastrointestinal, hematopoietic, and dermatological effects. Comprehensive toxicology studies including acute, subchronic, and chronic toxicity, genotoxicity, and reproductive toxicity would be required for regulatory approval. The compound is intended for research use only and is not approved for human therapeutic use. Proper handling procedures including use of personal protective equipment are recommended.
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| References | |
| Additional Infomation |
(3S,5S,6R)-Navtemadlin (CAS# 2459946-14-4) is a potent and selective inhibitor of MDM2. Also known as (3S,5S,6R)-AMG 232 or (3S,5S,6R)-KRT-232, it is a stereoisomer of the MDM2 inhibitor Navtemadlin. The compound binds to MDM2 and disrupts the MDM2-p53 interaction, leading to the activation of p53 and induction of apoptosis in cancer cells. (3S,5S,6R)-Navtemadlin is intended for research use only and is not for human therapeutic use.
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| Molecular Formula |
C28H35CL2NO5S
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|---|---|
| Molecular Weight |
568.552205324173
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| Exact Mass |
567.161
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| CAS # |
2459946-14-4
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| Related CAS # |
Navtemadlin;1352066-68-2
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| PubChem CID |
145864877
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| Appearance |
White to off-white solid powder
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| LogP |
5.8
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
37
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| Complexity |
912
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| Defined Atom Stereocenter Count |
4
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| SMILES |
N1([C@H](CS(C(C)C)(=O)=O)C(C)C)[C@@H](C2=CC=C(Cl)C=C2)[C@H](C2=CC=CC(Cl)=C2)C[C@@](C)(CC(O)=O)C1=O
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| InChi Key |
DRLCSJFKKILATL-CBZDIVBHSA-N
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| InChi Code |
InChI=1S/C28H35Cl2NO5S/c1-17(2)24(16-37(35,36)18(3)4)31-26(19-9-11-21(29)12-10-19)23(20-7-6-8-22(30)13-20)14-28(5,27(31)34)15-25(32)33/h6-13,17-18,23-24,26H,14-16H2,1-5H3,(H,32,33)/t23-,24+,26-,28-/m0/s1
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| Chemical Name |
2-[(3S,5S,6R)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-1-[(2S)-3-methyl-1-propan-2-ylsulfonylbutan-2-yl]-2-oxopiperidin-3-yl]acetic acid
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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 (175.89 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 | 1.7589 mL | 8.7943 mL | 17.5886 mL | |
| 5 mM | 0.3518 mL | 1.7589 mL | 3.5177 mL | |
| 10 mM | 0.1759 mL | 0.8794 mL | 1.7589 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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