| 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) .
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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 .
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| 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 .
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| 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 .
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| 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 .
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| 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) .
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| References |
[1]. https://www.invivochem.cn/product/V61718
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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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