Isoxazole-9

2022-08-17: Nootropics reference: Metamind reddit longpost: The role of Isoxazole-9 on invitro & invivo neurogenesis and cognitive enhancement

Isoxazole-9 #

• Effects of Isx-9 and stress on adult hippocampal neurogenesis: Experimental considerations and future perspectives
  • It is also noteworthy that Isx-9-induced activation of endogenous neuronal gene programs is able to inhibit differentiation of neural progenitors into other cell types, even in the presence of strong gliogenic signals
• Isoxazole-9 reduces enhanced fear responses and retrieval in ethanol-dependent male rats
• Differential Effects of Isoxazole-9 on Neural Stem/Progenitor Cells, Oligodendrocyte Precursor Cells, and Endothelial Progenitor Cells
  • Slightly increased the number of NSPCs and effectively induced neuronal differentiation of NSPCs.
  • Significantly decreased OPC number in a concentration-dependent manner, suggesting cytotoxicity.
    • Blank: This is due to Ca2+ influx. isx-9 and Curcumin both potentiate wnt signaling and inhibit hdac but curcumin’s ‘off targets’ also protect oligodendrocytes. It’s well-known in the literature that WNT signaling downregulates OPC, but enhances mature ones.
  • Did not affect EPC cell number. But in a matrigel assay of angiogenesis, Isx-9 significantly inhibited tube formation in outgrowth endothelial cells derived from EPCs. This potential anti-tube-formation effect of Isx-9 was confirmed in a brain endothelial cell line.
• Isoxazole 9 (ISX9), a small molecule targeting Axin, activates Wnt/β‐catenin signalling and promotes hair regrowth (Jan 2023)
  • Axin1 inhibitor (which in most places increases β-Catenin). Increases neurogenesis without depleting stem cell pool.
• Therapeutic blood-brain barrier modulation and stroke treatment by a bioengineered FZD4-selective WNT surrogate in mice
• Functional and mechanistic exploration of an adult neurogenesis-promoting small molecule
• ISX-9 potentiates CaMKIIδ-mediated BMAL1 activation to enhance circadian amplitude

• Blank: Permanently improved memory but also my limbs get numb/cold easier. It’s too fucking schizo to even talk about. I used to have almost complete amnesia of parts of my life but isx9 completely reversed that allowing me to freely move within my memories, at least if I put enough effort into it. This also made me feel more whole as a person (remembering is metabolically intensive, take skq1).
  • it also remains possible that Isx-9 enhances dendritic complexity via an as-yet unidentified cell intrinsic or circuit-level change
  • ~15mg IN
• Brotherman: I megadoses intranasal multiple times. It feels so weird on my ears and brain but makes music way better and makes my brain so much more functionally awake. Weird side effects but super powerful with intranasal, sharpens mind a lot. What else activates wnt/beta-catenin as much as isx-9 then? The effects are phenomenal and the top 3 most powerful nootropics i have taken.
  • Potentiates my AMPAR expression in the Substantia Nigra similar to TAK-653.
  • GSK3α/β is a negative regulator of β-catenin, these studies imply that reducing activity of the Wnt pathway increases the vulnerability to depression, mania, psychosis, and autistic behavior. Wnt/β-catenin signaling in brain development and mental disorders: keeping TCF7L2 in mind
  • Can cause rage and mania