Sidorova, Yulia A. published the artcileA novel small molecule GDNF receptor RET agonist, BT13, promotes neurite growth from sensory neurons in vitro and attenuates experimental neuropathy in the rat, Synthetic Route of 330161-87-0, the publication is Frontiers in Pharmacology (2017), 365/1-365/18, database is CAplus and MEDLINE.
Neuropathic pain caused by nerve damage is a common and severe class of chronic pain. Disease-modifying clin. therapies are needed as current treatments typically provide only symptomatic relief; show varying clin. efficacy; and most have significant adverse effects. One approach is targeting either neurotrophic factors or their receptors that normalize sensory neuron function and stimulate regeneration after nerve damage. Two candidate targets are glial cell line-derived neurotrophic factor (GDNF) and artemin (ARTN), as these GDNF family ligands (GFLs) show efficacy in animal models of neuropathic pain (Boucher et al., 2000; Gardell et al., 2003; Wang et al., 2008, 2014). As these protein ligands have poor drug-like properties and are expensive to produce for clin. use, we screened 18,400 drug-like compounds to develop small mols. that act similarly to GFLs (GDNF mimetics). This screening identified BT13 as a compound that selectively targeted GFL receptor RET to activate downstream signaling cascades. BT13 was similar to NGF and ARTN in selectively promoting neurite outgrowth from the peptidergic class of adult sensory neurons in culture, but was opposite to ARTN in causing neurite elongation without affecting initiation. When administered after spinal nerve ligation in a rat model of neuropathic pain, 20 and 25mg/kg of BT13 decreased mech. hypersensitivity and normalized expression of sensory neuron markers in dorsal root ganglia. In control rats, BT13 had no effect on baseline mech. or thermal sensitivity, motor coordination, or weight gain. Thus, small mol. BT13 selectively activates RET and offers opportunities for developing novel disease-modifying medications to treat neuropathic pain.
Frontiers in Pharmacology published new progress about 330161-87-0. 330161-87-0 belongs to indole-building-block, auxiliary class Protein Tyrosine Kinase/RTK,Src, name is SU6656, and the molecular formula is C8H11NO, Synthetic Route of 330161-87-0.
Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles