[CAS NO. 1313367-56-4] NVP-CGM097sulfate
PRODUCTS SPECIFICATIONS [1313367-56-4]
DESCRIPTION [1313367-56-4]
Overview
| MDL | MFCD31382179 |
|---|---|
| Molecular Weight | 757.34 |
| Molecular Formula | C38H49ClN4O8S |
| SMILES | ClC(C=C1)=CC=C1[C@@H](C2=CC(OC(C)C)=C(OC)C=C2C3)N(C4=CC=C(N(C[C@@H]5CC[C@@H](N6CC(N(C)CC6)=O)CC5)C)C=C4)C3=O.O=S(O)(O)=O |
Summary
NVP-CGM097 sulfate is a potent and selective MDM2 inhibitor with IC 50 of 1.7±0.1 nM for hMDM2 .
IC50 & Target
IC50 & Target: IC50: 1.7±0.1 nM (hMDM2) [1]
In Vitro
NVP-CGM097 binds to human MDM2 with an IC 50 of 1.7 nM and shows high selectivity over MDM4 (IC 50 =2000 nM). NVP-CGM097 is about four times more potent than Nutlin-3a (IC 50 =8 nM). In addition, NVP-CGM097 shows no significant activity against Bcl-2:Bak, Bcl-2:Bad, Mcl-1:Bak, Mcl-1:NOXA, XIAP:BIR3, and c-IAP:BIR3 protein-protein interactions. NVP-CGM097 significantly inhibits the proliferation of cells expressing wild-type p53, while sparing the p53 null cells with a 35-58-fold difference. NVP-CGM097 is able to significantly redistribute wild-type p53 into the cell nucleus with an IC 50 of 0.224 μM, demonstrating its ability to inhibit the p53:MDM2 interaction in living cells. NVP-CGM097 significantly inhibits the proliferation of cells expressing wild-type p53, while sparing the p53 null cells with a 35-58-fold difference. NVP-CGM097 inhibtis HCT116 (p53 WT/WT ) with IC 50 of 454±136 nM [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
NVP-CGM097 is able to inhibit the interaction between p53 and MDM2 and reactivate the p53 pathway in a MDM2-amplified SJSA-1 human tumor model, as judged by elevation of p21 mRNA levels, a pharmacodynamic (PD) indicator for p53 activity. p21 mRNA levels are found to increase concomitantly with levels of NVP-CGM097 in tumor-bearing rats dosed at 30 mg/kg. The PD response is biphasic and prolonged up to 24 h. Additional p53 target genes such as MDM2 and PUMA mRNA levels are assessed in the tumor samples as well and showed a similar behavior. Daily treatment with NVP-CGM097 dose dependently and significantly inhibits SJSA-1 tumor growth in rats. It promotes stable disease at 20 mg/kg, which is associated with a plasma AUC 0-24 of 163 μM•h. After iv administration, the total blood clearance (CL) of NVP-CGM097 is 5 mL/min per kg for mouse, 7 mL/min per kg for rat, 3 mL/min per kg for dog, and 4 mL/min per kg for monkey. The apparent terminal half-life (t 1/2 ) is long in rodents and monkey (6-12 h) but is comparatively longer in dogs (20 h). After oral dosing, NVP-CGM097 is well absorbed with T max occurring between 1 and 4.5 h in all species tested [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT01760525 | Novartis Pharmaceuticals|Novartis |
Solid Tumor With p53 Wild Type Status
|
March 20, 2013 | Phase 1 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Solvent & Solubility
DMSO : 100 mg/mL ( 132.04 mM ; Need ultrasonic)
H 2 O : 100 mg/mL ( 132.04 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.3204 mL | 6.6021 mL | 13.2041 mL |
| 5 mM | 0.2641 mL | 1.3204 mL | 2.6408 mL |
| 10 mM | 0.1320 mL | 0.6602 mL | 1.3204 mL |
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1.
Add each solvent one by one: PBS
Solubility: 50 mg/mL (66.02 mM); Clear solution; Need ultrasonic
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2.
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3.
Add each solvent one by one: 10% DMSO >> 90% (20% SBE-β-CD in saline)
Solubility: ≥ 2.5 mg/mL (3.30 mM); Clear solution
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4.
Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 2.5 mg/mL (3.30 mM); Clear solution