Frakefamide

Frakefamide
Clinical data
Other names	L-Tyrosyl-D-alanyl-4-fluoro-L-phenylalanyl-L-phenylalaninamide
ATC code	None;
Identifiers
	IUPAC name (2S)-2-[(2R)-2-[(2S)-2-amino-3-(4-hydroxyphenyl)propanamido]propanamido]-N-[(1S)-1-carbamoyl-2-phenylethyl]-3-(4-fluorophenyl)propanamide;
CAS Number	188196-22-7;
PubChem CID	9829352;
ChemSpider	8005088;
UNII	DM32B4GU70;
CompTox Dashboard (EPA)	DTXSID701030318 ;
Chemical and physical data
Formula	C30H34FN5O5
Molar mass	563.630 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C[C@H](C(=O)N[C@@H](CC1=CC=C(C=C1)F)C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)N)NC(=O)[C@H](CC3=CC=C(C=C3)O)N;
	InChI InChI=1S/C30H34FN5O5/c1-18(34-29(40)24(32)15-20-9-13-23(37)14-10-20)28(39)36-26(17-21-7-11-22(31)12-8-21)30(41)35-25(27(33)38)16-19-5-3-2-4-6-19/h2-14,18,24-26,37H,15-17,32H2,1H3,(H2,33,38)(H,34,40)(H,35,41)(H,36,39)/t18-,24+,25+,26+/m1/s1; Key:GTPHQORJKFJIRB-JTQLPTLWSA-N;

Frakefamide (INN) is a synthetic, fluorinated linear tetrapeptide with the amino acid sequence Tyr-D-Ala-(p-F)Phe-Phe-NH₂ which acts as a peripherally-specific, selective μ-opioid receptor agonist.^[1]^[2] Despite its inability to penetrate the blood-brain-barrier and enter the central nervous system,^[1] frakefamide has potent analgesic effects and, unlike centrally-acting opioids like morphine, does not produce respiratory depression, indicating that its antinociceptive effects are mediated by peripheral μ-opioid receptors.^[1]^[3] It was under development for the treatment of pain by AstraZeneca and Shire but was shelved after phase II clinical trials.^[4]^[5]

References

^ ^a ^b ^c Modalen ÅÖ, Quiding H, Frey J, Westman L, Lindahl S (March 2005). "A novel molecule (frakefamide) with peripheral opioid properties: the effects on resting ventilation compared with morphine and placebo". Anesthesia and Analgesia. 100 (3): 713–717. doi:10.1213/01.ANE.0000145011.75545.C5. PMID 15728057. S2CID 23249323.
^ Aronson JK (30 November 2009). Meyler's Side Effects of Analgesics and Anti-Inflammatory Drugs. Elsevier. p. 84. ISBN 978-0-444-53273-2. Retrieved 27 April 2012.
^ Modalen AO, Quiding H, Frey J, Westman L, Lindahl S (January 2006). "A novel molecule with peripheral opioid properties: the effects on hypercarbic and hypoxic ventilation at steady-state compared with morphine and placebo". Anesthesia and Analgesia. 102 (1): 104–109. doi:10.1213/01.ANE.0000184254.85567.80. PMID 16368813. S2CID 40297091.
^ Anderson NG (15 April 2012). "Introduction". Practical Process Research and Development: A Guide for Organic Chemists. Academic Press. p. 4. ISBN 978-0-12-386537-3. Retrieved 27 April 2012.
^ Schmidt WK (13 May 2003). "An overview of current and investigational drugs for the treatment of acute and chronic pain". In Bountra C, Munglani R, Schmidt WK (eds.). Pain: Current Understanding, Emerging Therapies, And Novel Approaches To Drug Discovery. CRC Press. p. 400. ISBN 978-0-8247-8865-0. Retrieved 27 April 2012.