Deconstructing the Iboga Alkaloid Skeleton: Potentiation of FGF2-induced Glial Cell Line-Derived Neurotrophic Factor Release by a Novel Compound.
ACS chemical biology January 15, 2016 Madalee M Gassaway, Teresa L Jacques, Andrew C Kruegel et al. 23 citations
A novel iboga analog, XL-008, induces release of glial cell line-derived neurotrophic factor (GDNF) in C6 glioma cells. It also potentiates GDNF release induced by fibroblast growth factor 2 (FGF2), increasing potency more than 2-fold (from 7.85 ± 2.59 ng/mL to 3.31 ± 0.98 ng/mL) and efficacy more than 3-fold. The GDNF release by both XL-008 and the FGF2/XL-008 mixture is mediated through the MEK and PI3K signaling pathways but not through PLCγ. This work describes a small-molecule approach to modulating growth factor signaling in the brain, relevant to treating neuropsychiatric disorders such as depression, anxiety, and addiction.