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Gambogic amide is a potent and selective agonist of TrkA and also induces its tyrosine phosphorylation and activation of downstream signaling, including Akt and MAPK. Gambogic amide specifically interacts with the cytoplasmic juxtamembrane domain of the TrkA receptor and triggers its dimerization, leading to activation. Gambogic amide has neuroprotective activity preventing glutamate-induced neuronal cell death. Gambogic amide has improved efficacy in a transient middle cerebral artery occlusion model of stroke and could be used to study neurodegenerative diseases and stroke[1].

[1] Jang SW, et al. Gambogic amide, a selective agonist for TrkA receptor that possesses robust neurotrophic activity, prevents neuronal cell death. Proc Natl Acad Sci U S A. 2007 Oct 9;104(41):16329-34. DOI:10.1073/pnas.0706662104