| Name | MX69 |
| Description | MX69 is the MDM2/XIAP inhibitor, blocking the MDM2 protein-XIAP RNA interaction, leading to MDM2 degradation. |
| Cell Research | 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.(Only for Reference) |
| In vitro | 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-mediated inhibition of XIAP is MDM2 dependent. Treatment of MX69 activates caspases 3, 7, and 9 as well as the cleavage of the death substrate PARP. 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. MX69-induced cell death is indeed due to apoptosis. MX69-induced cell apoptosis and death are dependent on MDM2, p53, and XIAP expression. MX69 shows minimal inhibitory effect on normal human bone marrow in vitro[1]. |
| In vivo | MX69 has significant apoptotic and anti-proliferative effects on MDM2-expressing cancer cells 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. Thus, specific MDM2 inhibitors such as MX69 may be excellent candidates for targeted therapy of refractory cancers expressing high levels of MDM2[1]. |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| Solubility Information | DMSO : 88 mg/mL (185.4 mM)
H2O : < 1 mg/mL (insoluble or slightly soluble)
Ethanol : 39 mg/mL (82.2 mM)
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| Keywords | E1/E2/E3 Enzyme | inhibit | E3 ligating enzyme | MX-69 | Ubiquitin ligase | IAP | E1 activating enzyme | E2 conjugating enzyme | Ubiquitin conjugating enzyme | Inhibitor | MX 69 | MX69 | Ubiquitin activating enzyme | MDM-2/p53 |
| Inhibitors Related | Milademetan | NSC697923 | XI-006 | PYZD-4409 | Nutlin-3 | NAcM-OPT | NSC232003 | Xevinapant | NAE-IN-M22 | Indole-3-carbinol | Idasanutlin | RITA |
| Related Compound Libraries | Cuproptosis Compound Library | Bioactive Compound Library | Ubiquitination Compound Library | HIF-1 Signaling Pathway Compound Library | Autophagy Compound Library | Pyroptosis Compound Library | Inhibitor Library | Anti-Aging Compound Library | Bioactive Compounds Library Max | Anti-Cancer Active Compound Library |
United States
