6alpha-ethyl-chenodeoxycholic acid (6-ECDCA), a potent and selective FXR agonist endowed with anticholestatic activity.
A series of 6alpha-alkyl-substituted analogues of chenodeoxycholic acid (CDCA) were synthesized and evaluated as potential farnesoid X receptor (FXR) ligands. Among them, 6alpha-ethyl-chenodeoxycholic acid (6-ECDCA) was shown to be a very potent and selective FXR agonist (EC(50) = 99 nM) and to be endowed with anticholeretic activity in an in vivo rat model of cholestasis.
Pellicciari
Roberto
R
Fiorucci
Stefano
S
Camaioni
Emidio
E
Clerici
Carlo
C
Costantino
Gabriele
G
Maloney
Patrick R
PR
Morelli
Antonio
A
Parks
Derek J
DJ
Willson
Timothy M
TM
D000818:Animals; D000924:Anticholesteremic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D002635:Chenodeoxycholic Acid / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002779:Cholestasis / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D004268:DNA-Binding Proteins / Q000819:agonists*; D006801:Humans; D008024:Ligands; D008099:Liver / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000819:agonists*; D000099150:Receptor, Farnesoid X-Activated
D000924:Anticholesteremic Agents; D002635:Chenodeoxycholic Acid; D004268:DNA-Binding Proteins; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D000099150:Receptor, Farnesoid X-Activated; C464660:obeticholic acid