Is NorUDCA a Conjugated Form of UDCA?
No, norursodeoxycholic acid (norUDCA) is not a conjugated form of UDCA—it is a structurally distinct side-chain-shortened derivative of UDCA. 1, 2
Structural and Chemical Differences
NorUDCA is a C23 homologue of UDCA, created by shortening the side chain by one carbon atom, whereas UDCA is a C24 bile acid 2, 3, 4
The key distinguishing feature is that norUDCA is relatively resistant to amidation (conjugation with glycine or taurine), which fundamentally differentiates it from UDCA both structurally and pharmacologically 2, 3
UDCA undergoes efficient conjugation with glycine or taurine in the liver, which is the standard metabolic pathway for bile acids 5
Pharmacological Implications of Non-Conjugation
Because norUDCA remains largely unconjugated, it undergoes "cholehepatic shunting", allowing it to target bile ducts directly and induce bicarbonate-rich hypercholeresis with cholangioprotective effects 2, 3
Paradoxically, conjugation is essential for the anticholestatic effect of norUDCA in hepatocellular cholestasis models—when norUDCA is conjugated to taurine (TnorUDCA), it demonstrates significantly improved anticholestatic properties compared to unconjugated norUDCA 5
The resistance to conjugation gives norUDCA distinct therapeutic properties including anti-cholestatic, anti-inflammatory, anti-fibrotic, and antiproliferative effects that differ from standard UDCA 6, 2, 3
Clinical Context
NorUDCA is being investigated as a novel therapeutic agent for PSC, with phase II trials showing dose-dependent reductions in alkaline phosphatase levels (up to -26% at 1,500mg/d) with an excellent safety profile 1, 4
NorUDCA remains investigational with no completed large phase III trials for any indication, and no published histological fibrosis endpoint data exists in human trials 6
The European Association for the Study of the Liver identifies norUDCA as a distinct "novel bile acid-based therapeutic option" separate from UDCA, alongside FXR agonists and other emerging therapies 1