Al-Ali, Hassan; Ding, Ying; Slepak, Tatiana; Wu, Wei; Sun, Yan; Martinez, Yania; Xu, Xiao-Ming; Lemmon, Vance P.; Bixby, John L. published the artcile< The mTOR substrate S6 kinase 1 (S6K1) is a negative regulator of axon regeneration and a potential drug target for central nervous System Injury>, Formula: C24H15F3N4O, the main research area is central nervous system injury axon regeneration mTOR SK; S6K; axon regeneration; drug discovery; drug target; kinase; spinal cord injury.
The mammalian target of rapamycin (mTOR) pos. regulates axon growth in the mammalian central nervous system (CNS). Although axon regeneration and functional recovery from CNS injuries are typically limited, knockdown or deletion of PTEN, a neg. regulator of mTOR, increases mTOR activity and induces robust axon growth and regeneration. It has been suggested that inhibition of S6 kinase 1 (S6K1, gene symbol: RPS6KB1), a prominent mTOR target, would blunt mTOR’s pos. effect on axon growth. In contrast to this expectation, we demonstrate that inhibition of S6K1 in CNS neurons promotes neurite outgrowth in vitro by twofold to threefold. Biochem. anal. revealed that an mTOR-dependent induction of PI3K signaling is involved in mediating this effect of S6K1 inhibition. Importantly, treating female mice in vivo with PF-4708671, a selective S6K1 inhibitor, stimulated corticospinal tract regeneration across a dorsal spinal hemisection between the cervical 5 and 6 cord segments (C5/C6), increasing axon counts for at least 3 mm beyond the injury site at 8 wk after injury. Concomitantly, treatment with PF-4708671 produced significant locomotor recovery. Pharmacol. targeting of S6K1 may therefore constitute an attractive strategy for promoting axon regeneration following CNS injury, especially given that S6K1 inhibitors are being assessed in clin. trials for nononcol. indications.
Journal of Neuroscience published new progress about Central nervous system injury. 1223001-51-1 belongs to class naphthyridine, and the molecular formula is C24H15F3N4O, Formula: C24H15F3N4O.
Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem