Description
A-484954 is an ATP-competitive inhibitor of eukaryotic elongation factor-2 kinase (eEF-2K; IC
50 = 420 nM). It reduces eEF-2K autophosphorylation in PC3, HeLa, H460, H1299, and MDA-MB-231 cancer cells when used at a concentration of 75 μM.
Uses
7-AMino-1-cyclopropyl-3-ethyl-1,2,3,4-tetrahydro-2,4-dioxopyrido[2,3-d]pyriMidine-6-carboxaMide,a pyrido[2,3-d]pyrimidin-2,4(1H,3H)-dione derivative with potential use as herbicide antidote.
Uses
A-484954 has been used a selective and potent inhibitor to inhibit eEF2K (eukaryotic elongation factor 2 kinase), in order to check the enhancement of synaptic transmission in the stratum radiatum of the hippocampal CA1 region. It has also been used as an eEF2K inhibitor to monitor real-time luminescence of U2OS Arntl::dLUC cells.
Biochem/physiol Actions
A-484954 is a potent, selective inhibitor of eukaryotic longation factor-2 kinase (eEF2K). Eukaryotic elongation factor-2, which is required for protein synthesis, is inactivated upon phosphorylation by eEF2K.
in vivo
A484954 causes relaxation in E (+) and E (-) aorta or mesenteric artery precontracted with NA. Pretreatment with L-NAME but not indomethacin or cimetidine partially inhibits the A484954-induced relaxation in mesenteric artery[2].
Long-term A-484954 treatment inhibits MCT-induced increases PA pressure. It is revealed that A-484954 inhibits MCT-induced PA hypertrophy and fibrosis but not impairment of endothelium-dependent and -independent relaxation. Furthermore, A-484954 inhibits MCT-induced NADPH oxidase-1 expression and ROS generation as well as matrix metalloproteinase-2 activation[3].
References
[1] RAMAKRISHNA EDUPUGANTI . Synthesis and biological evaluation of pyrido[2,3-d]pyrimidine-2,4-dione derivatives as eEF-2K inhibitors[J]. Bioorganic & Medicinal Chemistry, 2014, 22 17: Pages 4910-4916. DOI:
10.1016/j.bmc.2014.06.050
![7-AMino-1-cyclopropyl-3-ethyl-1,2,3,4-tetrahydro-2,4-dioxopyrido[2,3-d]pyriMidine-6-carboxaMide Structure](https://www.chemicalbook.com/CAS/GIF/142557-61-7.gif)
