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MX69

Cat. No. M8895
MX69 Structure
Size Price Availability Quantity
10mg USD 240 In stock
50mg USD 950 In stock
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Quality Control
  • Current batch:
  • Purity >98%
  • COA
  • MSDS
Biological Activity

MX69 is a dual inhibitor of MDM2 and XIAP that binds to MDM2 RING protein with binding Kd values of 2.34 μM. MX69 inhibits expression of both MDM2 and XIAP in a time- and dose-dependent manner. MX69 induces ubiquitination of endogenous MDM2 in cancer cells.

Downregulation of MDM2 by MX69 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 MX69 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 MX69 significantly inhibits expression and increased the turnover of WT-MDM2 but not MDM2-C464A. MX69 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 MX69-treated cells. MX69 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.

In vivo, MX69 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 MX69 at the 100 mg/kg dose. MDM2-specific agent MX69 should not activate either on-target (e.g., p53 induction) or off-target signaling pathways in normal cells.

Protocol
Cell Experiment
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)
Preparation method The cytotoxic effect of leads is determined using the WST assay. Briefly, cells cultured in 96-well microtiter plates are treated with different concentrations of leads 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.
Concentrations 0-10 μM
Incubation time 24 h
Animal Experiment
Animal models
Formulation
Dosages
Administration
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information
Molecular Weight 474.57
Formula C27H26N2O4S
CAS Number 1005264-47-0
Purity >98%
Solubility DMSO: ≥ 60 mg/mL
Storage at -20°C
References

Discovery of Dual Inhibitors of MDM2 and XIAP for Cancer Treatment.
Gu L, et al. Cancer Cell. 2016 Oct 10;30(4):623-636. PMID: 27666947.

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  Catalog
Abmole Inhibitor Catalog 2017




Keywords: MX69 supplier, Mdm2, inhibitors

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