XIB4035
GFRα1 agonist / A novel small molecule thought to be an agonist at the glial cell line-derived neurotrophic factor (GDNF) family receptor α-1 GFRα-1. It inhibits radiolabeled GDNF binding in Neuro-2A cells in a concentration dependent manner IC50=10.4 μM. Like GDNF, it induced Ret autophosphorylation and promoted neurite outgrowth in Neuro-2A cells1. Recent studies indicate that it enhances GFRα family receptor signaling in conjunction with ligand stimulation. Effective treatment for small-fiber neuropathy in mouse models of the disease.2,3 GDNF agonists may be a new class of Parkinson’s disease therapeutics.4
Biochemicals & reagents
10023-54-8
1) Tokugawa et al. (2003), XIB4035, a novel nonpeptidyl small molecule agonist for GFRalpha-1; Neurochem. Int., 42 81 2) Hedstrom et al. (2014), Treating small fiber neuropathy by topical application of a small molecule modulator of ligand-induced GFRα/RET receptor signaling; Proc. Natl. Acad. Sci. USA, 111 2325 3) Hsieh et al. (2018) Distinct TrkA and Ret Modulated negative and positive neuropathic behaviors in a mouse model of resiniferatoxin-induced small fiber neuropathy; Exp. Neurol., 300 87 4) Drinkut et al. (2016) Ret is essential to mediate GDNF’s neuroprotective and neuroregenerative effect in Parkinson disease mouse model; Cell Death Dis. 7 e2359
RT
PATHWAY: Neurotrophin; Proliferation -- RESEARCH AREA: Neuroscience -- DISEASE AREA: Neurodegeneration