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NVP-CGM097

Name: NVP-CGM097
Brand: Selleck Chemicals
SKU: S7875
Rating: 5 (5 reviews)

Catalog No.S7875 Synonyms: CGM-097

For research use only.

NVP-CGM097 is a highly potent and selective MDM2 inhibitor with Ki value of 1.3 nM for hMDM2 in TR-FRET assay. It binds to the p53 binding-site of the Mdm2 protein, disrupting the interaction between both proteins, leading to an activation of the p53 pathway.

CAS No. 1313363-54-0

Selleck's NVP-CGM097 has been cited by 5 Publications

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MDM2/MDMX Signaling Pathway Map

Biological Activity

Description

Targets

MDM2 ^[1]
(Cell-free assay)

1.7 nM

In vitro

NVP-CGM097 binding to MDM2 is species dependent. It was shown to be selective for the p53:MDM2 interaction compared to the p53:MDM4 interaction (1176-fold selectivity) and the Ras:Raf interaction (3000-fold selectivity). In addition, NVP-CGM097 showed 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 was 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. NVP-CGM097 treatment leads to p53 nuclear translocation that results in cell growth inhibition in a p53-dependent manner^[1].

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Formulation	Activity Description	PMID

SJSA1 cells	MWLGeY5kfGmxbjDhd5NigQ>?	NGq1WYlKdmirYnn0bY9vKG:oIHPlcIwheHKxbHnm[ZJifGmxbjDv[kBpfW2jbjDTTnNCOSClZXzsd{whT0l3ME2wMlM2KM7:TR?=	Mn33NlYyQDF6NUG=
HCT116 cells	NEnuXoVHfW6ldHnvckBie3OjeR?=	NGLac\|JKdmirYnn0bY9vKG:oIHPlcIwheHKxbHnm[ZJifGmxbjDv[kBpfW2jbjDIR3QyOTZiY3XscJMh\XiycnXzd4lv\yCyNUOsJGlEPTB;MD60OVQh\|ryP	M2TabFI3OThzOEWx
PC3 cells	NVPRZVJHTnWwY4Tpc44h[XO\|YYm=	MWnJcohq[mm2aX;uJI9nKG2WT2LDNkBqdiCqdX3hckBRSzNiY3XscJMh[XO\|ZYPz[YQh[XNiaX7obYJqfGmxbjDv[kBCU1RicHjvd5Bpd3K7bHH0bY9vKGG2IGO0O\|Mh[W[2ZYKgNUBpeixiSVO1NF0xNjB{MjFOwG0>	M4nCd\|I3OTB{NUC2

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In vivo

After iv administration, the total blood clearance (CL) of NVP-CGM097 was 5 mL/min/kg for mouse, 7 mL/min/kg for rat, 3 mL/min/kg for dog, and 4 mL/min/kg for monkey. On the basis of the respective hepatic blood flows, NVP-CGM097 showed a consistent low total blood CL in all species (5-10% of hepatic blood flow). The apparent terminal half-life (t1/2) was long in rodents and monkey (6-12 h) but was comparatively longer in dogs (20 h). After oral dosing, the compound was well absorbed with Tmax occurring between 1 and 4.5 h in all species tested. The oral bioavailability (%F) was high in mouse, rat, and dog and moderate in monkey. NVP-CGM097 was 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. p21 mRNA levels were found to increase concomitantly with levels of compound 1 in tumor-bearing rats dosed at 30 mg/kg. Daily treatment with NVP-CGM097 dose dependently and significantly inhibited SJSA-1 tumor growth in rats^[1].

Protocol (from reference)

Cell Research:^[2]

Cell lines: Bon1 cells, NCI-H727 cells, Got1 cells
Concentrations: 0.1 nM-2500 nM
Incubation Time: 48 hrs, 96 hrs, 144 hrs or 216 hrs
Method: Cells were seeded in appropriate densities (Bon1 cells: 1500 cells/well, NCI-H727 cells: 2000 cells/well, Got1 cells: 50000 cells/well) into 96-well plates and grown for 24 hrs in complete medium containing serum/antibiotic. The next day, the cells were incubated with various concentrations of NVP-CGM097 (0.1 nM-2500 nM), 5-fluorouracil (100 nM-100 µM), streptozotocin (1 nM-100 µM), temozolomide (1 µM-1 mM), everolimus (10 nM) or octreotide (100 nM-10 µM) in 10 % FBS medium (antibiotic-free). After 48 hrs, 96 hrs, 144 hrs or 216 hrs the metabolic activity was measured with "Cell Titer 96 Aqueous One Solution" cell proliferation assay. The measurement was performed at 492 nm with an ELISA plate reader.

Animal Research:^[1]

Animal Models: Sprague-Dawley rat
Dosages: 1 mg/kg
Administration: i.v.

References

Solubility (25°C)

In vitro

Chemical Information

Molecular Weight	659.26
Formula	C₃₈H₄₇ClN₄O₄
CAS No.	1313363-54-0
Storage	3 years	-20°C	powder
Storage	2 years	-80°C	in solvent
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

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In vivo Formulation Calculator (Clear solution)

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