Aminoquinol

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.1Recent 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] KIMIKO TOKUGAWA . XIB4035, a novel nonpeptidyl small molecule agonist for GFRα-1[J]. Neurochemistry international, 2003, 42 1: Pages 81-86. DOI:10.1016/s0197-0186(02)00053-0
[2] KRISTIAN L HEDSTROM. Treating small fiber neuropathy by topical application of a small molecule modulator of ligand-induced GFRα/RET receptor signaling.[J]. Proceedings of the National Academy of Sciences of the United States of America, 2014: 2325-2330. DOI:10.1073/pnas.1308889111
[3] YU-LIN HSIEH . Distinct TrkA and Ret modulated negative and positive neuropathic behaviors in a mouse model of resiniferatoxin-induced small fiber neuropathy[J]. Experimental Neurology, 2018, 300: Pages 87-99. DOI:10.1016/j.expneurol.2017.10.026
[4] ANJA DRINKUT. Ret is essential to mediate GDNF’s neuroprotective and neuroregenerative effect in a Parkinson disease mouse model[J]. Cell Death & Disease, 2016, 7 9: e2359-e2359. DOI:10.1038/cddis.2016.263