NVP-CGM097 sulfate - ≥98% , CAS No.1313367-56-4

CAS: 1313367-56-4 Cat. No.: N649940 Molecular Weight: 659.26 PubChem CID: 53262550

GRADE & PURITY ≥98%

Storage

Store at 2-8°C,Desiccated

Shipped In

Wet ice

Overview

NVP-CGM097 sulfate is a potent and selective MDM2 inhibitor with IC 50 of 1.7±0.1 nM for hMDM2 .

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 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 cells with a 35-58-fold difference. NVP-CGM097 inhibtis HCT116 (p53 WT/WT ) with IC 50 of 454±136 nM. 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 . MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Form:Solid

IC50& Target:IC50 & Target: IC50: 1.7±0.1 nM (hMDM2)

Specifications

Specifications & Purity

≥98%

Biochemical and Physiological Mechanisms

NVP-CGM097 sulfate is a potent and selective MDM2 inhibitor with IC 50 of 1.7±0.1 nM for hMDM2 .

Storage

Store at 2-8°C, Desiccated

Shipped In

Wet ice

This product requires cold chain shipping. Ground and other economy services are not available.

Action Type

INHIBITOR

Purity

≥98%

Names and Identifiers

• Canonical Smiles: CC(C)OC1=C(C=C2CC(=O)N(C(C2=C1)C3=CC=C(C=C3)Cl)C4=CC=C(C=C4)N(C)CC5CCC(CC5)N6CCN(C(=O)C6)C)OC.OS(=O)(=O)O
• IUPAC Name: (1S)-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;sulfuric acid
• InChIKey: YFLKIFVIZIALIA-GHVGLMRRSA-N
• INCHI: 1S/C38H47ClN4O4.H2O4S/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;1-5(2,3)4/h8-11,14-17,20,22,25-26,31,38H,6-7,12-13,18-19,21,23-24H2,1-5H3;(H2,1,2,3,4)/t26?,31?,38-;/m0./s1
• Isomeric 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.OS(=O)(=O)O
• PubChem CID: 53262550
• Molecular Weight: 659.26

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Class Tetrahydroisoquinolines
      • Subclass 1-phenyltetrahydroisoquinolines

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Class: Tetrahydroisoquinolines
• Subclass: 1-phenyltetrahydroisoquinolines
• Intermediate Tree Nodes: Not available
• Direct Parent: 1-phenyltetrahydroisoquinolines
• Alternative Parents: Isoquinolones and derivatives Alpha amino acids and derivatives Aniline and substituted anilines Anisoles Dialkylarylamines Alkyl aryl ethers N-methylpiperazines Cyclohexylamines Chlorobenzenes Organic sulfuric acids Aryl chlorides Tertiary carboxylic acid amides Trialkylamines Lactams Azacyclic compounds Carbonyl compounds Hydrocarbon derivatives Organic oxides Organochlorides Organopnictogen compounds
• Molecular Framework: Aromatic heteropolycyclic compounds
• Substituents: 1-phenyltetrahydroisoquinoline - Isoquinolone - Alpha-amino acid or derivatives - Anisole - Phenol ether - Tertiary aliphatic/aromatic amine - Aniline or substituted anilines - Dialkylarylamine - Alkyl aryl ether - Sulfuric acid - Halobenzene - Cyclohexylamine - Chlorobenzene - N-methylpiperazine - N-alkylpiperazine - Piperazine - Aryl halide - 1,4-diazinane - Monocyclic benzene moiety - Aryl chloride - Benzenoid - Tertiary carboxylic acid amide - Organic sulfuric acid or derivatives - Amino acid or derivatives - Tertiary aliphatic amine - Carboxamide group - Tertiary amine - Lactam - Carboxylic acid derivative - Azacycle - Ether - Organooxygen compound - Amine - Organopnictogen compound - Carbonyl group - Organic oxygen compound - Hydrocarbon derivative - Organic oxide - Organonitrogen compound - Organochloride - Organohalogen compound - Organic nitrogen compound - Aromatic heteropolycyclic compound
• Description: This compound belongs to the class of organic compounds known as 1-phenyltetrahydroisoquinolines. These are compounds containing a phenyl group attached to the C1-atom of a tetrahydroisoquinoline moiety.
• External Descriptors: Not available

Data sources

1. Djoumbou Feunang Y, Eisner R, Knox C, Chepelev L, Hastings J, Owen G, Fahy E, Steinbeck C, Subramanian S, Bolton E, Greiner R, and Wishart DS. ClassyFire: Automated Chemical Classification With A Comprehensive, Computable Taxonomy. Journal of Cheminformatics, 2016, 8:61.

DOI: 10.1186/s13321-016-0174-y

Chemical and Physical Properties

• Solubility: DMSO : 100 mg/mL (132.04 mM; Need ultrasonic) H2O : 100 mg/mL (132.04 mM; Need ultrasonic)
• Molecular Weight: 757.300 g/mol
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 10
• Rotatable Bond Count: 9
• Exact Mass: 756.296 Da
• Monoisotopic Mass: 756.296 Da
• Topological Polar Surface Area: 149.000 Ų
• Heavy Atom Count: 52
• Formal Charge: 0
• Complexity: 1120.000
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 1
• Undefined Atom Stereocenter Count: 0
• Defined Bond Stereocenter Count: 0
• Undefined Bond Stereocenter Count: 0
• The total count of all stereochemical bonds: 0
• Covalently-Bonded Unit Count: 2

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