XIB4035 (10023-54-8) is a novel small molecule thought to be an agonist at the glial cell line-derived neurotrophic factor (GDNF) family receptor GFRα-1. It inhibits radiolabeled GDNF binding in Neuro-2A cells in a concentration dependent manner IC50?= 10.4 μM. Like GDNF, XIB4035 induced Ret autophosphorylation and promoted neurite outgrowth in Neuro-2A cells.1?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
1) Tokugawa?et al. (2003),?XIB4035, a novel nonpeptidyl small molecule agonist for GFRα-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
