product name MX69
Description: MX69 is a potent and seletive MDM2/XIAP inhibitor that is useful for cancer treatment. MX69 blocks the MDM2 protein-XIAP RNA interaction, leading to MDM2 degradation. MX69 shows minimal inhibitory effect on normal human hematopoiesis in vitro and is very well tolerated in animal models. MX69-induced MDM2 downregulation results not only in inhibition of XIAP expression, but also in activation of p53, which contributes to cancer cell apoptosis in vitro and inhibition of cancer cell proliferation in vivo.
References: Cancer Cell. 2016 Oct 10;30(4):623-636.
474.57
Formula
C27H26N2O4S
CAS No.
1005264-47-0
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 95 mg/mL (200.2 mM)
Water: <1 mg/mL
Ethanol: 41 mg/mL (86.4 mM)
Solubility (In vivo)
Synonyms
other peoduct :
| In Vitro |
In vitro activity: 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. Kinase Assay: Cell Assay: The cytotoxic effect of leads on 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) 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. |
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| 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. |
| Animal model | |
| Formulation & Dosage | |
| References | Cancer Cell. 2016 Oct 10;30(4):623-636. |
