Home Apoptosis MDM2/MDMX inhibitor MX69

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MX69 MDM2/MDMX inhibitor

MX69 is a MDM2/XIAP inhibitor that binds to MDM2 RING protein with binding Kd values of 2.34 μM. It is used for cancer treatment.

MX69 MDM2/MDMX inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 474.57

Purity & Quality Control

Batch: S840301 DMSO]95 mg/mL]false]Ethanol]41 mg/mL]false]Water]Insoluble]false Purity: 99.99%
99.99

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Signaling Pathway

MDM2/MDMX Signaling Pathways

MDM2/MDMX Signaling Pathway

Mechanism of Action

Targets
MDM2 [1]
(Cell-free assay)
2.34 μM(Kd)

In vitro
In vitro MX69 inhibits expression of both MDM2 and XIAP in a time- and dose-dependent manner. This compound induces ubiquitination of endogenous MDM2 in cancer cells. Downregulation of MDM2 by this chemical is through induction of MDM2 self-ubiquitination and degradation. Half-life of MDM2 in control-treated EU-1 cells is greater than 90 min, whereas this compound treatment decreases the MDM2 half-life to <30 min. In SK-N-SH cells with stably transfected either wild-type (WT)-MDM2 or mutant MDM2-C464A, Treatment with this compound significantly inhibits expression and increased the turnover of WT-MDM2 but not MDM2-C464A. This compound significantly enhances the p53 half-life in WT-MDM2 but not mutant MDM2-C464A-transfected SK-N-SH cells. p53 is stabilized and accumulates in this compound-treated cells. This compound-mediated inhibition of XIAP is MDM2 dependent. Treatment of this chemical activates caspases 3, 7, and 9 as well as the cleavage of the death substrate PARP. This compound also exhibits a significant cytotoxic effect on both ALL and NB lines(cancer cell lines), particularly those lines with MDM2 overexpression and a WTp53 phenotype. This compound-induced cell death is indeed due to apoptosis. This compound-induced cell apoptosis and death are dependent on MDM2, p53, and XIAP expression. This compound shows minimal inhibitory effect on normal human bone marrow in vitro[1].
Cell Research Cell lines six ALL cell lines (EU-1, EU-3, EU-6, EU-8, SUP-B13, and UOC-B1) and six NB cell lines (NB-1691, NB-1643, SH-EP1, IMR-32, SK-NSH, and LA1-55N)
Concentrations 0-10 μM
Incubation Time 24 h
Method The cytotoxic effect of MX69 is determined using the WST assay. Briefly, cells cultured in 96-well microtiter plates are treated with different concentrations of this compound for a 20-hr period. WST (25 mg/well) is then added and incubation continued for an additional 4 hr, after which the optical density is read with a microplate reader.

In Vivo
In vivo MX69 has significant apoptotic and anti-proliferative effects on MDM2-expressing cancer cells in vivo. This compound is well tolerated in animals due to the fact that normal cells/tissues express little or no MDM2. No evidence of toxicity after treatment with this chemical at the 100 mg/kg dose. This MDM2-specific agent should not activate either on-target (e.g., p53 induction) or off-target signaling pathways in normal cells. Thus, specific MDM2 inhibitors such as this compound may be excellent candidates for targeted therapy of refractory cancers expressing high levels of MDM2[1].

References
  • https://pubmed.ncbi.nlm.nih.gov/27666947/

Chemical Information

Molecular Weight 474.57 Formula

C27H26N2O4S
CAS No. 1005264-47-0 SDF Download SDF
Synonyms N/A
Smiles CC1=C(C=C(C=C1)NS(=O)(=O)C2=CC3=C(C=C2)NC(C4C3C=CC4)C5=CC=C(C=C5)C(=O)O)C

Storage and Stability

Storage (From the date of receipt)

In vitro
Batch:

DMSO : 95 mg/mL ( (200.18 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 41 mg/mL

Water : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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