BT44

BT44 is a selective RET activator. BT44 can penetrate through the blood-brain barrier and can be used for the research of neurodegenerative disorders and diabetes mellitus. In Vitro BT44 (7.5-75 μM; 15 min) promotes RET phosphorylation and selectively activates downstream cascades in the cells expressing GFL receptors. BT44 (0.5-10 μM; 16-20 h) promotes neurite outgrowth from sensory neurons. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Western Blot AnalysisCell Line: GFRα3-transfected MG87RET cells Concentration: 7.5, 18, 35 and 75 μM Incubation Time: 15 min Result: Increased RET and ERK phosphorylation. In Vivo 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 . 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 . 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. BT44 (10 mg/kg; i.v.) penetrates the blood-brain barrier and is rapidly eliminated from the circulation (half-life (t 1/2 ) = 0.72 h) and brain (t 1/2 = 0.47 h) in rats. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Wistar rats, spinal nerve ligation (SNL) and Streptozotocin (STZ; HY-13753)-induced diabetes mellitus models Dosage: 5, 12.5 or 25 mg/kg Administration: Subcutaneous injecton, every second day for 10, 42 or 14 days Result: Alleviated mechanical allodynia in the SNL animals. Treatment with the dose of 5 mg/kg alleviated mechanical hyperalgesia in the STZ-treated animals, while the 12.5 mg/kg dose was not effective. Concentration of 5 mg/kg attenuated cold allodynia in the STZ-treated animals during the first two weeks while the effect of 12.5 mg/kg was not significant. Animal Model: Wistar rats, SNL-induced diabetes mellitus model Dosage: 12.5 or 25 mg/kg Administration: Subcutaneous injecton, every second day for 10 days Result: Led to a significant increase in the number of IB4 expressing neurons in the ipsilateral DRGs. The 12.5 mg/kg dose protected IB4-positive neurons from SNL-induced lesion. Form:Solid

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