EBE-A22

EBE-A22 is a N-methyl derivative of PD-153035 which exhibits a very high affinity and selectivity for the epidermal growth factor receptor tyrosine kinase (EGF-R TK) and shows a remarkable cytotoxicity against several types of tumor cell lines. Nevertheless, EBE-A22 retains a high cytotoxic profile while having no effect on EGF-R TK. EBE-A22 and PD-153035 both bind to DNA and act like typical intercalating agents, according to the results of a variety of optical and gel electrophoresis analyses. More specifically, as one might anticipate from an intercalating agent, EBE-A22 unwinds supercoiled plasmid, stabilizes duplex DNA against heat denaturation, and generates negative CD and ELD signals. DNase I footprinting experiments on a wide variety of DNA substrates demonstrate that EBE-A22 interacts preferentially with GC-rich sequences and discriminates against homooligomeric runs of A and T, which are frequently cut more easily by the enzyme in the presence of the drug than the control. However, PD153035 does not exhibit these properties. All things considered, the findings indicate that this N-methylated ring system is a promising candidate for the synthesis of DNA-targeted cytotoxic compounds and offer the first experimental proof that anilinoquinazoline derivatives target DNA. The potential significance of specific DNA binding for an activity is examined. The surprising GC-selective binding characteristics of EBE-A22 call for more research into the potential applications of N-methylanilinoquinazoline derivatives as instruments for the synthesis of DNA binding ligands that are sequence-specific.

*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.