Casokefamide

Casokefamide
Clinical data
Other names	L-tyrosyl-D-alanyl-L-phenylalanyl-D-alanyl-L-tyrosinamide
ATC code	None;
Identifiers
	IUPAC name (2S)-2-[(2R)-2-[(2S)-2-[(2R)-2-[(2S)-2-amino-3-(4-hydroxyphenyl)propanamido]propanamido]-3-phenylpropanamido]propanamido]-3-(4-hydroxyphenyl)propanamide;
CAS Number	98815-38-4;
PubChem CID	5464104;
ChemSpider	4576538;
UNII	B453T1E8MP;
ChEMBL	ChEMBL2106384;
CompTox Dashboard (EPA)	DTXSID30243827 ;
Chemical and physical data
Formula	C33H40N6O7
Molar mass	632.718 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES O=C(N[C@@H](C(=O)N[C@H](C(=O)N[C@@H](C(=O)N[C@H](C(=O)N)Cc1ccc(O)cc1)C)Cc2ccccc2)C)[C@@H](N)Cc3ccc(O)cc3;
	InChI InChI=1S/C33H40N6O7/c1-19(36-32(45)26(34)16-22-8-12-24(40)13-9-22)31(44)39-28(18-21-6-4-3-5-7-21)33(46)37-20(2)30(43)38-27(29(35)42)17-23-10-14-25(41)15-11-23/h3-15,19-20,26-28,40-41H,16-18,34H2,1-2H3,(H2,35,42)(H,36,45)(H,37,46)(H,38,43)(H,39,44)/t19-,20-,26+,27+,28+/m1/s1; Key:XDRHVZLDLNGKLM-FLVVDCEDSA-N;

Casokefamide (INN), also known as β-casomorphin 4027 (β-CM-4027) and [D-Ala^2,4,Tyr⁵]-β-casomorphin-5-amide, is a peripherally-specific, synthetic opioid pentapeptide with the amino acid sequence Tyr-D-Ala-Phe-D-Ala-Tyr-NH₂.^[1] Derived from the β-casomorphin sequence, it was designed with the intention of improving resistance to digestive enzymes so that it could be used as an antidiarrheal medicine.^[1]^[2] Unlike other casomorphins, which are generally selective μ-opioid receptor agonists, casokefamide binds to both the μ- and δ-opioid receptors.^[1] In a clinical study, casokefamide was found to be effective via the oral route for the treatment of chronic diarrhea, and did not produce any side effects.^[2] However, further clinical development was not pursued and it was never marketed.

References

^ ^a ^b ^c Brantl V, Picone D, Amodeo P, Temussi PA (March 1993). "Solution structure of casokefamide". Biochemical and Biophysical Research Communications. 191 (3): 853–9. doi:10.1006/bbrc.1993.1295. PMID 8466524.
^ ^a ^b Schulte-Frohlinde E, Reindl W, Bierling D, et al. (March 2000). "Effects of oral casokefamide on plasma levels, tolerance, and intestinal transit in man". Peptides. 21 (3): 439–42. doi:10.1016/S0196-9781(00)00166-2. PMID 10793229. S2CID 44670226.