From:  Dimeric dipeptide mimetics of neurotrophins as molecular tools and potential neuroprotective drugs

The relationships between the diverse pharmacological activities of NGF, BDNF, and NT-3 dipeptide mimetics, their patterns of post-receptor signaling activation, and the nature of the parent neurotrophins

Activation patterns of post-receptor signaling pathways of Trk receptors by dipeptide mimetics of neurotrophins    
Parent neurotrophinsNGFBDNFNT-3NGFBDNFBDNFNT-3
Dipeptide mimeticGTS-115GK-61GSB-106GTS-302GK-2GSB-214GTS-201GTS-301
Neuroprotective activityIn vitro++++++++
In vivo+ns++++++nsns
Antidiabetic activityNot assessedNot assessed+Not assessed++++ns+
Memory-enhancing activityNot assessednsns+++ns+
Antidepressant-likeNot assessed+++++++ns+
Anxiolytic activityNot assessednot assessed++Not assessedns+ns
Effect on pain sensitivityNot assessed↑↓↓↓nsNot assessed↓
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NGF: nerve growth factor; BDNF: brain-derived neurotrophic factor; NT-3: neurotrophin-3; ns: non significant; GK-2: bis-(monosuccinyl-L-glutamyl-L-lysine) hexamethylenediamide; GK-6: bis-(N-aminocaproyl-glycyl-L-lysine) hexamethylenediamide; GTS-115: bis-(N-gamma-oxybutyryl-L-lysyl-L-histidine) hexamethylenediamide; GSB-106: bis-(N-monosuccinyl-L-seryl-L-lysine) hexamethylenediamide; GSB-214: bis-(N-monosuccinyl-L-methionyl-L-serine) heptamethylenediamide; GTS-201: bis-(N-hexanoyl-L-seryl-L-lysine) hexamethylenediamide; GTS-301: bis-(N-monosuccinyl-L-asparaginyl-L-asparagine) hexamethylenediamide; GTS-302: bis-(N-gamma-oxybutyryl-L-glutamyl-L-asparagine) hexamethylenediamide. All effects not labeled as “ns” are statistically significant. ↑: increase in pain thresholds; ↓: decrease in pain thresholds; 1 Although NGF mimetics GTS-115 and GK-6 both activated all major post-receptor signaling cascades of Trk receptors, GK-6, in contrast to GTS-115, induced only short-term activation of the PI3K/Akt pathway. This presumably explains the lack of neuroprotective activity of GK-6 in vivo