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XIB4035 | GFR alpha 1 agonist

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

Focus Biomolecules cell signaling reagent supplier, chemical structure of XIB4035 | GFR alpha 1 agonist | CAS 10023-54-8

Catalog#  10-1486

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Catalog Number:
GFRα1 agonist
Chemical Name:
(E)-N4-(7-chloro-2-(2-chlorostyryl)quinolin-4-yl)-N1,N1-diethylpentane-1,4-diamine 3(H3PO4)
Molecular Weight:
Molecular Formula:
C26H31Cl2N3 3(H3PO4)
Soluble in DMSO (up to 25 mg/ml with warming).
Physical Properties:
Light brown solid
98% by TLC
NMR (Conforms)
Storage Temperature:
Stable for 2 years as supplied. Solutions in DMSO may be stored at -20° for up to 3 months.
Shipping Code:
Materials provided by Focus Biomolecules are for laboratory research use only and are not intended for human or veterinary applications.

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