The glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs) alleviate symptoms of experimental neuropathy, protect and stimulate the regeneration of sensory neurons in animal models of neuropathic pain, and restore their functional activity.  BT44 is a GDNF mimetic with improved biological activity. It selectively activates the major signal transduction unit of the GFL receptor complex, receptor tyrosine kinase RET for the research of neuropathic pain.

BT44 is a selective RET activator that can be used for the research of neurodegenerative disorders.

In vitro: Firstly, BT44 (7.5-75 μM; 15 min) promotes RET phosphorylation and selectively activates downstream cascades in the cells expressing GFL receptors. Secondly, BT44 (0.5-10 μM; 16-20 h) promotes neurite outgrowth from sensory neurons.

In vivo: Firstly, BT44 (5-25 mg/kg; s.c.; every second day for 10, 42 or 14 days) alleviates sensory signs in the SNL and STZ models of neuropathic. Secondly, BT44 (12.5 or 25 mg/kg; s.c.; every second day for 10 days) protects IB4-positive neurons in DRGs of animals with experimental neuropathy. Thirdly, BT44 (0.1 and 0.3 μg/24 h; infuse into the right dorsal striatum for 14 days) reverses amphetamine-induced motor imbalance and seems to protect dopaminergic fibers in the striatum in 6-OHDA rat model of Parkinson’s disease. Furthermore, BT44 (10 mg/kg; i.v.) can penetrate the blood-brain barrier and is rapidly eliminated from the circulation (t_1/2= 0.72 h) and brain (t_1/2 = 0.47 h) in rats.

In a word, BT44 is a selective RET activator. BT44 can be used for the research of neurodegenerative disorders and diabetes mellitus.

Reference:

[1] Haider MS, et al. Biomacromolecules. 2022;10.1021/acs.biomac.2c00761.

[2] Viisanen H, et al. Mol Pain. 2020 Jan-Dec;16:1744806920950866.