A quest for the stereo-electronic requirements for selective agonism for the neurotrophin receptors TrkA and TrkB in 17-spirocyclic-dehydroepiandrosterone derivatives.

ABSTRACT:

Introduction

The neurotrophin system plays a pivotal role in the development, morphology, and survival of the nervous system, and its dysregulation has been manifested in numerous neurodegenerative and neuroinflammatory diseases. Neurotrophins NGF and BDNF are major growth factors that prevent neuronal death and synaptic loss through binding with high affinity to their specific tropomyosin-related kinase receptors namely, TrkA and TrkB, respectively. The poor pharmacokinetic properties prohibit the use of neurotrophins as therapeutic agents. Our group has previously synthesized BNN27, a prototype small molecule based on dehydroepiandrosterone, mimicking NGF through the activation of the TrkA receptor.

Methods

To obtain a better understanding of the stereo-electronic requirem

SUBMITTER: Narducci D 

PROVIDER: S-EPMC10568017 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature