NRK1 inhibitors as a chemical class encompass a variety of compounds that indirectly influence the activity of Nicotinamide riboside kinase 1 (NRK1) through modulation of various cellular signaling pathways. NRK1 is a kinase involved in the phosphorylation of nicotinamide riboside and plays a role in the biosynthesis of nicotinamide adenine dinucleotide (NAD+). The compounds identified as inhibitors do not directly target NRK1 but impact the kinase indirectly by altering signaling pathways that can dictate the regulatory mechanisms of NRK1 activity.
These chemical inhibitors generally target kinases that are central to multiple signaling pathways, which ultimately contribute to the regulation of NRK1. Staurosporine, for instance, is a well-established kinase inhibitor that competes with ATP at the catalytic sites of a broad range of kinases, thereby reducing the phosphorylation activity of NRK1. LY294002 and Wortmannin are specific to the PI3K pathway, a crucial axis in cell survival and metabolism, which impacts the AKT signaling cascade and potentially the activity of NRK1. Rapamycin's inhibition of mTOR, a downstream component of the PI3K/AKT pathway, similarly affects NRK1 by altering the cellular environment and resource allocation for NAD+ biosynthesis. Furthermore, inhibitors like SP600125, U0126, SB203580, and PD98059 target various components of the MAPK signaling pathways, including JNK, MEK1/2, and p38. These pathways have broad cellular implications, including stress response and proliferation, which may intersect with NRK1 regulation.
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