TABLE 1.
Overview of affinity constants of microbial bile salt conjugates for the main host bile salt receptors
| Bile salt species | EC50 for TGR5 (µM) | EC50 for FXR (µM) |
|---|---|---|
| TLCA | 1.7 ± 0.1 | N.D. |
| CDCA | 32.7 ± 3.2 | 2.6 |
| GCDCA | 29.4 ± 0.9 | 8.6 |
| TCDCA | 26.1 ± 1.3 | 12.3 |
| LeuCDCA | 50.1 ± 7.4 | N.D. |
| PheCDCA | 59.2 ± 2.5 | N.D. |
| L-TyrCDCA | 88.9 ± 5.3 | 2.8/7.8 ± 2.9 |
| D-TyrCDCA | 93.7 ± 14.6 | N.D./6.8 |
| CA | 423.0 ± 39.6 | N.D. |
| GCA | 342.2 ± 26.7 | N.D. |
| TCA | 276.6 ± 16.6 | N.D. |
| LeuCA | 1149.8 ± 60.8 | N.D. |
| PheCA | 265.4 ± 67.5 | N.D. |
| L-TyrCA | Not calculable | N.D./46.3 |
| D-TyrCA | 528.5 ± 61.0 | N.D./9.9 |
Notes: EC50 values for TGR5 were derived from 4 independent cell-based nanoBRET assays. Those for FXR were obtained from a cell-free LanthaScreen coactivator assay, or in the case of a second column entry, a cell-based reporter assay. This reporter assay was repeated thrice for L-TyrCDCA. Data are presented as the average (± SD) of the means of independent replications. Abbreviations: CA, cholic acid; CDCA, chenodeoxycholic acid; D-TyrCA, D-Tyrosocholic acid; D-TyrCDCA, D-Tyrosochenodeoxycholic acid; FXR, farnesoid X receptor; GCA, glycocholic acid; GCDCA, glycochenodeoxycholic acid; LeuCA, leucocholic acid; LeuCDCA, leucochenodeoxycholic acid; L-TyrCA, L-Tyrosocholic acid; L-TyrCDCA, L-Tyrosochenodeoxycholic acid; nanoBRET, nano-luciferase bioluminescence resonance energy transfer; N.D., not determined; PheCA, phenylalanocholic acid; PheCDCA, Phenylalanochenodeoxycholic acid; TCA, Taurocholic acid; TCDCA, taurochenodeoxycholic acid; TGR5, Takeda G protein-coupled receptor 5; TLCA, taurolithocholic acid; TyrCA, tyrosocholic acid.