Table 2 Characteristics of kisspeptin receptor agonists
From: Advances in clinical applications of kisspeptin-GnRH pathway in female reproduction
Kisspeptin receptor agonists | Sequence | Affinity | Half-life (t½) | Potency (in vivo and in vitro) | BBB permeability | Related studies |
|---|---|---|---|---|---|---|
KP10 | H-Tyr-Asn-Trp-Asn-Ser-Phe-Gly-Leu-Arg-Phe-NH2 | Reference | 55 s to 4 min in humans and 34 s in mice | Reference | NO | (Beltramo and Decourt 2018; d'Anglemont de Tassigny et al. 2017 [73]; Jayasena et al. 2011 [51]) |
KP54 | H-Gly-Thr-Ser···Tyr-Asn-Trp-Asn-Ser-Phe-Gly-Leu-Arg-Phe-NH2 | Comparable | 1.3–1.8 h in humans and 32 min in mice (28 min in humans in one study (Dhillo et al. 2005)) | Comparable in vitro, higher in vivo | YES | (George et al. 2011 [77]; Abbara et al. 2020 [67]; d'Anglemont de Tassigny et al. 2017 [73]; Beltramo and Decourt 2018; Abbara, Clarke, and Dhillo 2021 [88]) |
FTM080 | 4-fluorobenzoyl-Phe-Gly-Leu-Arg-Trp-NH2 | Comparable | 6.6 h in murine serum | Comparable in vitro and lower in vivo | Maybe yes (it induces ovulation in musk shrews) | (Whitlock et al. 2015 [86]; Inoue et al. 2011) |
[dY](1)KP-10 | H-d-Tyr-Asn-Trp-Asn-Ser-Phe-Gly-Leu-Arg-Phe-NH2 | Lower in vitro | Unclear | Comparable in vitro and higher in vivo | Unclear | (Curtis et al. 2010 [87]) |
Compound 6 | palm-γ-Glutamyl-Tyr-Asn-Trp-Asn-Ser-GlyΨ[Tz]Leu-Arg(Me)-Tyr-NH2 | Higher | Longer than KP10 | Higher in vitro and in vivo | Probably Yes | (Decourt et al. 2016 [89]; Decourt et al. 2019) |
Compound 26 (KISS1-305) | H-Â d-Tyr-d-Pya(4)-Asn-Ser-Phe-azaGly-Leu-Arg(Me)-Phe-NH2 | Comparable | 6.76 min in rats | Higher in vitro | Probably Yes | |
TAK-448 (MVT-602) | Ac-d-Tyr-Hydroxyproline (Hyp)-Asn-Thr-Phe-azaGly-Leu-Arg(Me)-Trp-NH 2 | Comparable | 1.6-2.2 h in humans | Comparable in vitro and higher in vivo | YES | (Yoshida et al. 2012; Matsui et al. 2014 [92]; Abbara et al. 2020 [67]) |
TAK-683 | Ac-d-Tyr-d-Trp-Asn-Thr-Phe-azaGly-Leu-Arg(Me)-Trp-NH2 | Comparable | 1.18-17.94 h in humans | Comparable in vitro and higher in vivo | Unclear | (Yoshida et al. 2012; Matsui et al. 2014 [92]; Scott et al. 2013 [93]; Abbara et al. 2020 [67]; Rahayu et al. 2017) |
RF9 | 1-adamantane carbonyl-Arg-Phe-NH2 | Higher | 40 min in mare circulation | Lower in vitro | Unclear | (Liu and Herbison 2014 [94]; Min et al. 2015 [95]; Korthanke et al. 2017) |
Bz-Arg-Trp-NH2 | Bz-Arg-Trp-NH2 | Higher | 121 min in rat serum | Lower in vitro and comparable in vivo | Unclear | (Doebelin et al. 2016 [96]) |