RF9 (drug)

RF9 (drug)
Identifiers
	IUPAC name (1S,3S,5S,7S)-N-((S)-1-(((S)-1-Amino-1-oxo-3-phenylpropan-2-yl)amino)-5-guanidino-1-oxopentan-2-yl)adamantane-2-carboxamide;
CAS Number	876310-60-0;
PubChem CID	53320361;
ChemSpider	9866263;
ChEBI	CHEBI:140980;
ChEMBL	ChEMBL1672380;
CompTox Dashboard (EPA)	DTXSID001151466 ;
Chemical and physical data
Formula	C26H38N6O3
Molar mass	482.629 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES O=C(N[C@H]([C@](N[C@H](C(N)=O)CC4=CC=CC=C4)=O)CCCNC(N)=N)C1(CC(C3)C2)CC3CC2C1;
	InChI InChI=1S/C26H38N6O3/c27-23(33)21(14-15-5-2-1-3-6-15)32-24(34)20(7-4-8-30-26(28)29)31-25(35)22-18-10-16-9-17(12-18)13-19(22)11-16/h1-3,5-6,16-22H,4,7-14H2,(H2,27,33)(H,31,35)(H,32,34)(H4,28,29,30)/t16?,17?,18?,19?,20-,21-,22?/m0/s1; Key:ZLSDDXOZWMSRNZ-BFLAJNRSSA-N;

RF9 is a drug used in scientific research which acts as a potent and selective antagonist for the neuropeptide FF receptors NPFF1 and NPFF2, binding to both NPFF subtypes but with improved selectivity over related targets such as neuropeptide Y receptors compared to older drugs such as BIBP-3226. In animal studies, RF9 increased the analgesic effects of mu-opioid agonists while decreasing some side effects such as hyperalgesia.^[1]^[2]^[3]^[4]^[5]^[6]

References

^ Simonin F, Schmitt M, Laulin JP, Laboureyras E, Jhamandas JH, MacTavish D, et al. (2006). "RF9, a potent and selective neuropeptide FF receptor antagonist, prevents opioid-induced tolerance associated with hyperalgesia". Proceedings of the National Academy of Sciences. 103 (2): 466–471. Bibcode:2006PNAS..103..466S. doi:10.1073/pnas.0502090103. PMC 1326150. PMID 16407169.
^ Gibula-Tarlowska E, Kedzierska E, Piechura K, Silberring J, Kotlinska J (2019). "The influence of a new derivate of kisspeptin-10 – Kissorphin (KSO) on the rewarding effects of morphine in the conditioned place preference (CPP) test in male rats". Behavioural Brain Research. 372 112043. doi:10.1016/j.bbr.2019.112043. PMID 31226311.
^ Wojciechowski P, Andrzejewski K, Kaczyńska K (2020). "Intracerebroventricular Neuropeptide FF Diminishes the Number of Apneas and Cardiovascular Effects Produced by Opioid Receptors' Activation". International Journal of Molecular Sciences. 21 (23): 8931. doi:10.3390/ijms21238931. PMC 7728097. PMID 33255594.
^ Aquino NS, Mansano NS, Vieira FA, Silva KS, Gusmao DO, Anderson GM, et al. (2023). "RFamide-related Peptide 3 Signaling via Neuropeptide FF Receptor Stimulates Prolactin Secretion in Female Rats". Endocrinology. 164 (8) bqad102. doi:10.1210/endocr/bqad102. PMID 37403228.
^ Chen D, Zhang M, Zhang Q, Wu S, Yu B, Zhang X, et al. (2024). "The blockade of neuropeptide FF receptor 1 and 2 differentially contributed to the modulating effects on fentanyl-induced analgesia and hyperalgesia in mice". European Journal of Pharmacology. 969 176457. doi:10.1016/j.ejphar.2024.176457. PMID 38395375.
^ Tang H, Zhang T, Feng J, Zhang M, Xu B, Zhang Q, et al. (2024). "Neuropeptide FF prevented histamine- or chloroquine-induced acute itch behavior through non-NPFF receptors mechanism in male mice". Neuropeptides. 108 102481. doi:10.1016/j.npep.2024.102481. PMID 39504659.

[1] Simonin F, Schmitt M, Laulin JP, Laboureyras E, Jhamandas JH, MacTavish D, et al. (2006). "RF9, a potent and selective neuropeptide FF receptor antagonist, prevents opioid-induced tolerance associated with hyperalgesia". Proceedings of the National Academy of Sciences. 103 (2): 466–471. Bibcode:2006PNAS..103..466S. doi:10.1073/pnas.0502090103. PMC 1326150. PMID 16407169.

[2] Gibula-Tarlowska E, Kedzierska E, Piechura K, Silberring J, Kotlinska J (2019). "The influence of a new derivate of kisspeptin-10 – Kissorphin (KSO) on the rewarding effects of morphine in the conditioned place preference (CPP) test in male rats". Behavioural Brain Research. 372 112043. doi:10.1016/j.bbr.2019.112043. PMID 31226311.

[3] Wojciechowski P, Andrzejewski K, Kaczyńska K (2020). "Intracerebroventricular Neuropeptide FF Diminishes the Number of Apneas and Cardiovascular Effects Produced by Opioid Receptors' Activation". International Journal of Molecular Sciences. 21 (23): 8931. doi:10.3390/ijms21238931. PMC 7728097. PMID 33255594.

[4] Aquino NS, Mansano NS, Vieira FA, Silva KS, Gusmao DO, Anderson GM, et al. (2023). "RFamide-related Peptide 3 Signaling via Neuropeptide FF Receptor Stimulates Prolactin Secretion in Female Rats". Endocrinology. 164 (8) bqad102. doi:10.1210/endocr/bqad102. PMID 37403228.

[5] Chen D, Zhang M, Zhang Q, Wu S, Yu B, Zhang X, et al. (2024). "The blockade of neuropeptide FF receptor 1 and 2 differentially contributed to the modulating effects on fentanyl-induced analgesia and hyperalgesia in mice". European Journal of Pharmacology. 969 176457. doi:10.1016/j.ejphar.2024.176457. PMID 38395375.

[6] Tang H, Zhang T, Feng J, Zhang M, Xu B, Zhang Q, et al. (2024). "Neuropeptide FF prevented histamine- or chloroquine-induced acute itch behavior through non-NPFF receptors mechanism in male mice". Neuropeptides. 108 102481. doi:10.1016/j.npep.2024.102481. PMID 39504659.

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