Table 3 Estimated binding free energy and dissociation constant between putative substrates and human UGT2B10
Model | Substrate | Ligand | ΔG [Kcal/mol ± SD] | Kd [mM] |
|---|---|---|---|---|
UGT2B10 with UDPGlcA | Controls | Amitriptyline | −1.9 ± 0.2 | 39.0 |
Itraconazole | 19.0 ± 0.5 | 1.1 × 1017 | ||
Putative ligands | 4-hydroxy voriconazole | −1.0 ± 0.0 | 184.7 | |
Acetaminophen | −5.5 ± 0.0 | 0.1 | ||
Cyclosporine A | 154.9 ± 2.9 | 1.8 × 10118 | ||
Bilirubine | 6.9 ± 0.0 | 1.2 × 1015 | ||
Dihydroxy voriconazole | −0.6 ± 0.0 | 363.0 | ||
Hydroxy voriconazole | −1.2 ± 0.1 | 125.0 | ||
Lorazepam | −2.6 ± 0.0 | 12.4 | ||
Methotrexate | −0.5 ± 0.5 | 567.3 | ||
Methylprednisolone | 5.2 ± 0.1 | 6.2 × 106 | ||
Mycophenolic acid | −5.1 ± 0.1 | 0.2 | ||
Posaconazole | 17.6 ± 0.3 | 8.8 × 1015 | ||
UDCA-G1 | 2.2 ± 0.1 | 4.4 × 104 | ||
UDCA-G2 | 1.2 ± 0.1 | 8053.6 | ||
Ursodeoxycholic acid | 2.2 ± 0.1 | 4.4 × 104 | ||
Voriconazole | −1.0 ± 0.1 | 197.8 | ||
Voriconazole N-oxide | −2.3 ± 0.1 | 2.1 × 104 | ||
Voriconazole N-oxide intermediate UK-215,364 [35] | −6.4 ± 0.1 | 0.02 |