Chemicals classified as DDIAS inhibitors may not directly bind to or block the functional domain of DDIAS, but they can influence the cellular pathways that determine its activity. For instance, inhibitors like Olaparib, KU-55933, and NU7441 target enzymes such as PARP, ATM, and DNA-PK, which are pivotal in the DNA damage response (DDR). The DDR is a network of cellular pathways that detect and repair DNA lesions, and DDIAS is implicated in modulating this response, particularly by suppressing apoptosis in the presence of DNA damage.
By perturbing the DDR through various points of intervention, these compounds can alter the normal function of DDIAS. Etoposide and Camptothecin, through their actions on topoisomerases, escalate the level of DNA damage, potentially surpassing the capacity of DDIAS to suppress apoptosis, resulting in an indirect inhibitory effect. Similarly, Cisplatin and Aphidicolin introduce DNA lesions that could challenge the protective role of DDIAS. Cell cycle inhibitors like Chk1 Inhibitor - PF-477736, MK-1775, and VE-821 further demonstrate the indirect method of inhibiting DDIAS by disrupting the cell cycle checkpoints and the ATR-mediated signaling pathways that are integral to the DDR.
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