BiochemProbe — Life Science Research Reagents

NVP-CGM097 free base · Synonyms: CGM097

NVP-CGM097 is a potent and selective MDM2 inhibitor.

For research use only. Not for human or veterinary use.

Target MDM-2/p53 E1/E2/E3 Enzyme
Research area Cancer
Purity >98% Stock Inquire
Data Sheet SDS COA

NVP-CGM097 structure

CAS No.: 1313363-54-0

Download structure (.mol)

Pack sizes & pricing

Size Price SKU Stock
50 mg USD 490.00 BP-02486-50mg In stock Get quote
100 mg USD 780.00 BP-02486-100mg In stock Get quote
250 mg USD 1,570.00 BP-02486-250mg In stock Get quote
500 mg USD 2,500.00 BP-02486-500mg In stock Get quote
1 g USD 4,010.00 BP-02486-1g In stock Get quote
2 g USD 6,420.00 BP-02486-2g In stock Get quote

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Description

NVP-CGM097 is a potent and selective MDM2 inhibitor with IC50 of 1.7±0.1 nM for hMDM2.

Biological activity

In Vitro NVP-CGM097 binds to human MDM2 with an IC50 of 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). 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 IC50 of 0.224 μM, demonstrating its ability to inhibit the p53:MDM2 interaction in living cells. In addition, NVP-CGM097 activity against the p53:MDM2 interaction is assessed in proliferation assays using either wild-type p53 or p53 null 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 (p53WT/WT) with IC50 of 454±136 nM. In Vivo NVP-CGM097 is able to inhibit the interaction between p53 and MDM2 and reactivate the p53 pathway in vivo 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 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.

Identifiers

SMILES
COC1=CC2=C(C=C1OC(C)C)[C@@H](N(C(=O)C2)C1=CC=C(C=C1)N(C)CC1CCC(CC1)N1CCN(C)C(=O)C1)C1=CC=C(Cl)C=C1
InChIKey
CLRSLRWKONPSRQ-CPOWQTMSSA-N

Specifications

MW (average)
659.2570
Formula
C38H47ClN4O4
CAS No.
1313363-54-0
Physical state
Solid
Color
Off-white to yellow
Shipping
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage
Powder -20°C, 3 years , 4°C, 2 years ; In solvent -20°C, 1 year;

Solubility

Soluble in DMSO

Documents

References

[1]. Holzer P, et al. Discovery of a Dihydroisoquinolinone Derivative (NVP-CGM097): A Highly Potent and Selective MDM2 Inhibitor Undergoing Phase 1 Clinical Trials in p53wt Tumors. J Med Chem. 2015 Aug 27;58(16):6348-58

Same target

Search MDM-2/p53

Same research area

Search Cancer