DRAM activators represent a diverse class of chemicals that exert their effects on the protein DRAM (DNA damage-regulated autophagy modulator 1). DRAM plays a crucial role in autophagy, a cellular process involved in the degradation and recycling of cellular components. The selected chemicals, including Rapamycin, Torin 1, Resveratrol, Chloroquine, Spautin-1, SBI-0206965, Lithium Chloride, SB216763, Niclosamide, NSC 67078, LY294002, and Cisplatin, directly enhance the functional activity of DRAM through various mechanisms. Rapamycin and Torin 1 act as mTOR inhibitors, relieving mTORC1 suppression on DRAM expression and promoting autophagy. Resveratrol activates AMPK signaling, leading to increased DRAM expression and autophagy initiation. Chloroquine inhibits lysosomal function, stabilizing DRAM and enhancing autophagy. Spautin-1 inhibits USP10 and USP13, preventing ubiquitin-mediated degradation of DRAM. SBI-0206965, an AMPK inhibitor, suppresses AMPK signaling, leading to decreased DRAM expression and autophagy induction.
Lithium Chloride and SB216763 target GSK-3β, stabilizing DRAM and initiating autophagy. Niclosamide activates AMPK signaling, promoting DRAM-mediated autophagy. NSC 67078, a p53 inhibitor, prevents p53-mediated repression of DRAM, enhancing autophagy. LY294002 inhibits PI3K/AKT signaling, suppressing autophagic responses mediated by DRAM. Cisplatin induces DNA damage and activates the p53 pathway, leading to increased DRAM expression and autophagy initiation. These DRAM activators provide valuable tools for understanding and manipulating autophagic processes, offering insights into the intricate regulation of cellular homeostasis. The diversity of mechanisms employed by these chemicals highlights the complexity of autophagy regulation and the multifaceted role of DRAM in maintaining cellular balance.
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