| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
NVP-CGM097 specifically targets the human homolog of Mouse Double Minute 2 (HDM2 or MDM2). It binds to the p53-binding pocket on the surface of the MDM2 protein. The binding affinity (IC50) of NVP-CGM097 for MDM2 is approximately 1.7 ± 0.1 nM, demonstrating high potency. It shows significant selectivity for the p53-MDM2 interaction over other protein-protein interactions, such as p53-MDM4 (1176-fold selectivity) .
The (R)-NVP-CGM097 stereoisomer does not bind effectively to MDM2 and is considered inactive. The active (S)-stereoisomer (NVP-CGM097) targets MDM2 (murine double minute 2), an E3 ubiquitin ligase that negatively regulates p53 by promoting its degradation. NVP-CGM097 inhibits the MDM2-p53 protein-protein interaction, blocking MDM2-mediated ubiquitination of p53. This leads to stabilization and accumulation of p53 protein, activation of p53 target genes, and induction of apoptosis and cell cycle arrest in p53 wild-type cancer cells. The stereoisomer is used to distinguish MDM2-dependent from MDM2-independent effects. |
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| ln Vitro |
In vitro, NVP-CGM097 effectively inhibits the proliferation of cancer cells harboring wild-type p53 (p53wt) in a p53-dependent manner. For instance, in p53wt neuroendocrine tumor cells (GOT1), treatment with 2,500 nM NVP-CGM097 for 96 hours resulted in a significant reduction in cell viability to 47.7%. In ER-positive breast cancer cell lines (MCF-7, ZR75-1), sub-micromolar IC50 values (approx. 0.2 μM) were observed, while p53-mutant cells (T-47D) were resistant (IC50 ~7.2 μM). Mechanistically, it induces nuclear translocation of p53, increases the expression of p53 target proteins like p21 and PUMA, and leads to G1 and G2/M cell cycle arrest followed by apoptosis .
In vitro, the stereoisomer NVP-CGM097 (stereoisomer) shows little to no activity compared to the active NVP-CGM097 enantiomer. The active compound inhibits MDM2 binding to p53, stabilizes p53 protein, and activates p53 transcriptional activity, leading to apoptosis in cancer cell lines with wild-type p53. In contrast, the (R)-stereoisomer does not significantly displace p53 from MDM2 and fails to activate p53 or induce cell death. Therefore, this inactive stereoisomer is used as a negative control to validate that observed biological effects are specifically due to MDM2 inhibition rather than off-target effects. |
| ln Vivo |
In vivo, NVP-CGM097 demonstrates potent antitumor activity in mouse xenograft models. In the MDM2-amplified, p53wt SJSA-1 osteosarcoma model, oral administration of NVP-CGM097 at well-tolerated doses (e.g., 25, 50, 100 mg/kg daily) led to significant tumor growth inhibition and even regression. Efficacy was observed across various dosing schedules (from daily to twice per week). Furthermore, it showed efficacy in other p53wt models, including patient-derived xenografts (PDX) of liposarcoma, AML, and endocrine-resistant breast cancer, particularly in combination with other agents like fulvestrant or CDK4/6 inhibitors .
In vivo, the (R)-stereoisomer of NVP-CGM097 is not expected to exhibit antitumor activity due to its inability to bind MDM2 effectively. It is used as an inactive control compound in animal xenograft studies. The active NVP-CGM097 shows potent antitumor efficacy in preclinical models of p53 wild-type cancers. By including the inactive stereoisomer as a control, researchers can confirm that the antitumor effects of the active compound are specifically mediated through MDM2-p53 pathway engagement rather than non-specific toxicity or off-target mechanisms. |
| Enzyme Assay |
The primary binding affinity of NVP-CGM097 for MDM2 is typically determined using fluorescence polarization (FP) or time-resolved fluorescence resonance energy transfer (TR-FRET) assays. These cell-free assays utilize a recombinant MDM2 protein and a fluorescently labeled p53-derived peptide that mimics the transactivation domain of p53. The compound is serially diluted and incubated with the MDM2 protein and the labeled peptide. Upon binding, NVP-CGM097 displaces the labeled peptide from MDM2, causing a decrease in the fluorescence polarization or FRET signal, which is measured to calculate the IC50 value .
Cell-free MDM2-p53 binding assay: MDM2 protein (or the MDM2-p53 binding domain) is incubated with a fluorescently labeled p53-derived peptide (e.g., FITC-labeled p53 peptide corresponding to residues 17-29) in the presence of varying concentrations of test compound (including the active NVP-CGM097 and its inactive stereoisomer). Fluorescence polarization is measured to quantify displacement of the p53 peptide from MDM2. The inactive stereoisomer shows no significant displacement compared to the active compound, validating its use as a negative control in competition assays. |
| Cell Assay |
The primary binding affinity of NVP-CGM097 for MDM2 is typically determined using fluorescence polarization (FP) or time-resolved fluorescence resonance energy transfer (TR-FRET) assays. These cell-free assays utilize a recombinant MDM2 protein and a fluorescently labeled p53-derived peptide that mimics the transactivation domain of p53. The compound is serially diluted and incubated with the MDM2 protein and the labeled peptide. Upon binding, NVP-CGM097 displaces the labeled peptide from MDM2, causing a decrease in the fluorescence polarization or FRET signal, which is measured to calculate the IC50 value .
Cell-based p53 activation assay: p53 wild-type cancer cells (e.g., HCT116, RKO) are seeded in 96-well plates and treated with the active NVP-CGM097 or its inactive stereoisomer at various concentrations (e.g., 0.01-10 microM) for 24-48 hours. p53 protein levels are quantified by Western blot, and p53 transcriptional activity is measured using a luciferase reporter (p53-responsive element-luciferase). The inactive stereoisomer should produce no significant increase in p53 levels or transcriptional activity, confirming that the active compound's effects are specific to MDM2 inhibition rather than general cytotoxicity. |
| Animal Protocol |
A typical in vivo efficacy study involves female athymic nude mice bearing subcutaneous SJSA-1 xenografts. When tumors reach a certain size (e.g., ~200-300 mm³), mice are randomized into treatment groups (n=6-12 per group). NVP-CGM097 is formulated as an oral suspension and administered by oral gavage at various doses (e.g., 25, 50, 100 mg/kg) and schedules (e.g., daily for 14 days, or three times a week). Tumor volumes are measured twice weekly with calipers, and body weight is monitored as a proxy for toxicity. At the end of the study, tumors and plasma are collected for pharmacokinetic (PK) and pharmacodynamic (PD) analysis (e.g., measuring p21 mRNA levels) .
In vivo xenograft protocol: Female athymic nude mice bearing established p53 wild-type cancer xenografts (e.g., SJSA-1 osteosarcoma or HCT116 colon carcinoma) are randomized (n=8-10/group) and treated with the active NVP-CGM097, the inactive stereoisomer (at comparable doses), or vehicle control. Compounds are typically administered orally at doses of 10-100 mg/kg once daily or on a schedule (e.g., QD or QOD). Tumor volumes are measured twice weekly by calipers. The inactive stereoisomer group serves as a negative control, expected to show no tumor growth inhibition compared to vehicle. |
| ADME/Pharmacokinetics |
Pharmacokinetic data for the inactive stereoisomer are not available. The active NVP-CGM097 is orally bioavailable and has been characterized in preclinical species. The stereoisomer likely has similar absorption and distribution properties due to identical molecular weight and similar physicochemical properties (e.g., logP, solubility). However, as the compound is not intended for therapeutic use, detailed PK characterization is not a priority. It is used as a control tool, not for PK studies.
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| Toxicity/Toxicokinetics |
No toxicity studies have been conducted specifically for the inactive stereoisomer of NVP-CGM097, as it is not a drug candidate. The compound is a research-grade chemical used as a negative control in MDM2-p53 studies. The active NVP-CGM097 has been evaluated in preclinical toxicity studies and has shown acceptable tolerability profiles. The stereoisomer would not be expected to have significant toxicity at the concentrations used in control experiments (typically low micromolar in vitro and low mg/kg in vivo), but this is not formally established. Standard safety precautions apply.
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| References |
[1]. https://www.invivochem.cn/product/V61718
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| Additional Infomation |
NVP-CGM097 (stereoisomer) is not a drug and has no clinical applications or regulatory approval. It is a research-grade chemical used as a negative control in studies investigating the MDM2-p53 interaction. The active NVP-CGM097 (not this stereoisomer) has been investigated as a potential cancer therapeutic that activates p53 in wild-type p53 cancers. MDM2 inhibitors represent a promising class of anticancer agents. This stereoisomer is essential for rigorous controlled experiments to confirm that observed biological and antitumor effects are specifically due to MDM2 inhibition and not off-target activities or non-specific compound effects. Not for human use.
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| Molecular Formula |
C38H47CLN4O4
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|---|---|
| Molecular Weight |
659.26
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| Exact Mass |
658.328
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| Elemental Analysis |
C, 69.23; H, 7.19; Cl, 5.38; N, 8.50; O, 9.71
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| CAS # |
2070009-54-8
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| Related CAS # |
NVP-CGM097;1313363-54-0;NVP-CGM097 sulfate;1313367-56-4
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| PubChem CID |
124201616
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
6.5
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
47
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| Complexity |
1040
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC(C)OC1=C(C=C2CC(=O)N([C@@H](C2=C1)C3=CC=C(C=C3)Cl)C4=CC=C(C=C4)N(C)CC5CCC(CC5)N6CCN(C(=O)C6)C)OC
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| InChi Key |
CLRSLRWKONPSRQ-DUZTVQHZSA-N
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| InChi Code |
InChI=1S/C38H47ClN4O4/c1-25(2)47-35-22-33-28(20-34(35)46-5)21-36(44)43(38(33)27-8-10-29(39)11-9-27)32-16-14-30(15-17-32)41(4)23-26-6-12-31(13-7-26)42-19-18-40(3)37(45)24-42/h8-11,14-17,20,22,25-26,31,38H,6-7,12-13,18-19,21,23-24H2,1-5H3/t26?,31?,38-/m1/s1
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| Chemical Name |
(1R)-1-(4-chlorophenyl)-6-methoxy-2-[4-[methyl-[[4-(4-methyl-3-oxopiperazin-1-yl)cyclohexyl]methyl]amino]phenyl]-7-propan-2-yloxy-1,4-dihydroisoquinolin-3-one
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| Synonyms |
NVP-CGM097 (stereoisomer); NVP-CGM097 stereoisomer; (1R)-1-(4-chlorophenyl)-6-methoxy-2-[4-[methyl-[[4-(4-methyl-3-oxopiperazin-1-yl)cyclohexyl]methyl]amino]phenyl]-7-propan-2-yloxy-1,4-dihydroisoquinolin-3-one; 2643938-26-3;
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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: ≥ 241.5 mg/mL (366.32 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 | 1.5169 mL | 7.5843 mL | 15.1685 mL | |
| 5 mM | 0.3034 mL | 1.5169 mL | 3.0337 mL | |
| 10 mM | 0.1517 mL | 0.7584 mL | 1.5169 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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