NVP-CGM097

SKU: orb1296113

Description

NVP-CGM097 (CGM097) is a potent and selective small-molecule inhibitor of the MDM2-p53 interaction, exhibiting an IC50 of 1.7 nM against human MDM2. It is widely used in cancer research to reactivate p53 pathways, facilitating studies on tumor suppression in both cellular and animal models.

Research Area

Cell Biology, Protein Biochemistry

Key Properties

• CAS Number: 1313363-54-0
• MW: 659.26
• Purity: 98.92% (May vary between batches)
• Formula: C₃₈H₄₇ClN₄O₄
• SMILES: COc1cc2CC(=O)N([C@@H](c3ccc(Cl)cc3)c2cc1OC(C)C)c1ccc(cc1)N(C)C[C@H]1CC[C@@H](CC1)N1CCN(C)C(=O)C1
• Target: E1/E2/E3 Enzyme,Mdm2,MDM-2/p53
• Solubility: DMSO:48 mg/mL (72.81 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (3.03 mM);H2O:Insoluble

Bioactivity

• Target IC50:
  MDM2:1.7 nM
• In Vivo:
  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 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 AUC0-24 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 (t1/2) 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 Tmax occurring between 1 and 4.5 h in all species tested.
• In Vitro:
  NVP-CGM097 binds to human MDM2(IC50: 1.7 nM) and shows high selectivity over MDM4 (IC50: 2000 nM). NVP-CGM097 is about four times more potent than Nutlin-3a (IC50: 8 nM). 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 IC50 of 0.224 μM. 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 inhibits HCT116 (p53WT/WT, IC50: 454±136 nM).
• Cell Research:
  Two pairs of cell lines are used to assess NVP-CGM097 p53-dependent antiproliferative effects: (1) an isogenic pair of HCT116 cell lines either expressing wild-type p53 or knocked-out for the p53 gene and (2) a nonisogenic pair of osteosarcoma cell lines either endogenously expressing wild-type p53 and amplified for MDM2 (SJSA-1 cells) or null for p53 (SAOS-2 cells).
• Animal Research:
  Female athymic rats bearing subcutaneous xenotransplants of SJSA-1 tumors (n=5-12) are treated at 5, 10, 20, or 30 mg/kg or three times a week on Monday, Wednesday, and Friday (3qw M, W, F) at 30 or 70 mg/kg p.o for 14 days. Plasma AUCs are determined at the end of the study. Positive numbers indicate the percentage of tumor growth inhibition (T/C); negative numbers indicate the percentage of tumor regression.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

E1 activating enzyme, E1 Enzyme, E3Enzyme, E1/E2/E3 Enzyme, E1Enzyme, E2 conjugating enzyme, E2 Enzyme, E2Enzyme, E3 Enzyme, E3 ligating enzyme, CGM 097, CGM097, CGM-097, NVP CGM097, NVP-CGM 097, NVPCGM097, NVP-CGM097, NVP-CGM-097, inhibit, Inhibitor, MDM-2/p53, Mdm2, MDM2, Ubiquitin activating enzyme, Ubiquitin conjugating enzyme, Ubiquitin ligase

Compound Identifiers

PubChem CID

53240420