GFRα/RET Signaling Activator, XIB-4035

A cell-permeable chlorostyrylquinolinylbutylamino compound that was shown to competitively bind to glial cell line-derived neurotrophic factor (GDNF) family receptor-α1 (GFRα1) and act as an agonist (IC₅₀ = 10.4 µM for ¹²⁵I-GDNF binding in Neuro-2A cells) and induce autophosphorylation of RET protein. Elicits neurite outgrowth of Neuro-2A cells in a dose-dependent manner. However, some of the recent studies have questioned its agonist nature and have suggested that it acts as a positive modulator of ligand-Induced GFRα/RET signaling and prolongs the GDNF-induced RET phosphorylation. Shown to be effective in treating small fiber neuropathy caused by non-myelinating Schwann cell dysfunction in diabetic murine models leading to improved thermononiception. Does not appear to be toxic up to ~100 µM.

Please note that the molecular weight for this compound is batch-specific due to variable water content.

Cell permeable: yes

Primary Target
GFRα1

Reversible: yes

Target IC₅₀: 10.4 µM for ¹²⁵I-GDNF binding in Neuro-2A cells

Packaged under inert gas

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Use only fresh DMSO for reconstitution.

Hedstrom, K.L., et al. 2014. Proc. Natl. Acad. Sci. USA111, 2325.
Tokugawa, K., et al. 2003. Neurochem. Int.42, 81.

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Toxicity: Standard Handling (A)