ML264

ML264 is a novel and selective inhibitor of Krüppel-like factor 5 (KLF5) that potently inhibits the proliferation of colorectal cancer cells in vitro through modifications of the cell-cycle profile. Additionally, ML264 effectively stops the tumor's growth in 5 days in a well-established mouse xenograft model of colon cancer. Since ML264 potently inhibits the expression of KLF5 and EGR1, a transcriptional activator of KLF5, this effect is brought on by a marked decrease in proliferation. ML264 is highly active (IC50 = 29 nM is a cell-based assay for proliferation of DLD-1 cells, IC50 = 81 nM in a cell-based luciferase assay). The IEC-6 control cell line does not exhibit any cytotoxicity (IC50 >50 μM,<50% inhibition was observed at 100 μM). A number of other KLF5-expressing cell types (such as HCT116, IC50 = 560 nM; HT29, IC50 = 130 nM; and SW620, IC50 = 430 nM) also showed robust activity. An analysis of a panel of 47 selected kinases revealed that ML264 does not inhibit the kinases connected to the KLF5 pathway. By a large margin, ML264 lowers KLF5 expression, according to a Western blot analysis. These outcomes illustrate the target specificity of KLF5. According to a NCI60 panel study using ML264, the majority of colon cancer cell lines are killed off, and a number of other tumor cell lines are also affected by its cytotoxicity. Chemical stability, lack of reaction with glutathione, suitability for aqueous solubility, high stability to mouse, rat, and human hepatic microsomes, favorable characteristics related to drug-likeness, and lack of inhibition of CYP enzymes are all characteristics of ML264. It also has suitable aqueous solubility. These characteristics, combined with ML264's high cellular potency and selectivity, make it an excellent candidate for in vivo anticancer studies. It also has great potential for use in long-term in situ studies aimed at elucidating the function of KLF5 as a regulator of cellular proliferation and tumor formation in the intestinal epithelium. The potential of ML264 and its analogues as a novel therapeutic agent to stop the growth and spread of colorectal cancer is worth exploring.

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.