This study was performed in order to reveal the effect of Noopept (ethyl ester
of N-phenylacetyl-Lprolylglycine, GVS-111) on the DNA-binding
activity of transcriptional factors (TF) in HEK293 cells transiently
transfected with luciferase reporter constructs containing sequences for CREB,
NFAT, NF-κB, p53, STAT1, GAS, VDR, HSF1, and HIF-1. Noopept (10 μM)
was shown to increase the DNA-binding activity of HIF-1 only, while lacking the
ability to affect that of CREB, NFAT, NF-κB, p53, STAT1, GAS, VDR, and
HSF1. Noopept provoked an additional increase in the DNA-binding activity of
HIF-1 when applied in conditions of CoCl2-induced HIF- 1 stabilization. The
degree of this HIF-positive effect of Noopept was shown to be
concentration-dependent. Piracetam (1 mM) failed to affect significantly any of
the TF under study. The results of molecular docking showed that Noopept
(L-isomer), as well as its metabolite,
L-isomer of N-phenyl-acetylprolyl, unlike its
pharmacologically ineffective D-isomer, is able to bind to the
active site of prolyl hydroxylase 2. Taking into account the important role of
the genes activated by HIF-1 in the formation of an adaptive response to
hypoxia, data on the ability of Noopept to provoke a selective increase in the
DNA-binding activity of HIF-1 explain the wide spectrum of neurochemical and
pharmacological effects of Noopept revealed before. The obtained data allow one
to propose the HIF-positive effect as the primary mechanism of the activity of
this Pro-Gly-containing dipeptide.