Cystacyclin, a novel microbial metabolite with NGF mimetic activity

Nerve growth factor (NGF) is known to have key roles in neural protection and repair of central and peripheral neurons.1 NGF was reported to ameliorate several neuronal dysfunction and injury in animal models,2, 3 and has been applied to clinical trial.4 Because of its protein property, NGF is thought unsuitable for oral administration and insufficient for blood–brain barrier penetration. So far low-molecular-weight compounds having NGF mimetic activity have been screened and neurite-inducing compounds such as lactacystin5 and K-252a6 were isolated from microbial resources. A chemically synthesized compound of AIT-012 was reported to enhance NGF-induced neurite outgrowth and has been applied to clinical trail.7 In this report we describe isolation of a novel NGF mimetic compound and show its physico-chemical properties and biological activities of the compound named as cystacyclin.