Application | Comment | Organism |
---|---|---|
pharmacology | isoform UGT1A8173Ala/277Tyr variant exhibits no detectable glucuronidation activity against the trans isomers of either 4-hydroxytamoxifen or endoxifen. Little or no difference in tamoxifen glucuronidating activity is observed for the UGT1A8173Gly/277Cys or UGT1A10139Lys variants compared with their wild-type counterparts. For active hepatic UGTs, the UGT2B7268Tyr variant exhibits significant 2- and 5fold decreases in activity against the trans isomers of 4-hydroxytamoxifen and endoxifen, respectively, compared with wild-type UGT2B7268His. Functional polymorphisms in tamoxifen-metabolizing UGTs, including UGT2B7 and potentially UGT1A8, may be important in interindividual variability in tamoxifen metabolism and response to tamoxifen therapy | Homo sapiens |
Protein Variants | Comment | Organism |
---|---|---|
additional information | isoform UGT1A8173Ala/277Tyr variant exhibits no detectable glucuronidation activity against the trans isomers of either 4-hydroxytamoxifen or endoxifen. Little or no difference in tamoxifen glucuronidating activity is observed for the UGT1A8173Gly/277Cys or UGT1A10139Lys variants compared with their wild-type counterparts. For active hepatic UGTs, the UGT2B7268Tyr variant exhibits significant 2- and 5fold decreases in activity against the trans isomers of 4-hydroxytamoxifen and endoxifen, respectively, compared with wild-type UGT2B7268His | Homo sapiens |
KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
0.0037 | - |
trans-4-hydroxytamoxifen | isoform UGT2B7, variant 268His, pH 7.4, 37°C | Homo sapiens | |
0.0087 | - |
trans-4-hydroxytamoxifen | isoform UGT2B7, variant 268Tyr, pH 7.4, 37°C | Homo sapiens | |
0.013 | - |
trans-endoxifen | isoform UGTA10, variant 139Lys, pH 7.4, 37°C | Homo sapiens | |
0.023 | - |
trans-4-hydroxytamoxifen | isoform UGT1A8, variant 173Ala/277Cys, pH 7.4, 37°C | Homo sapiens | |
0.04 | - |
trans-endoxifen | isoform UGTA10, variant 139Glu, pH 7.4, 37°C | Homo sapiens | |
0.043 | - |
trans-4-hydroxytamoxifen | isoform UGT1A8, variant 173Gly/277Cys, pH 7.4, 37°C | Homo sapiens | |
0.052 | - |
trans-4-hydroxytamoxifen | isoform UGTA10, variant 139Lys, pH 7.4, 37°C | Homo sapiens | |
0.096 | - |
trans-4-hydroxytamoxifen | isoform UGTA10, variant 139Glu, pH 7.4, 37°C | Homo sapiens | |
0.098 | - |
trans-endoxifen | isoform UGT1A8, variant 173Ala/277Cys, pH 7.4, 37°C | Homo sapiens | |
0.101 | - |
trans-endoxifen | isoform UGT2B7, variant 268His, pH 7.4, 37°C | Homo sapiens | |
0.101 | - |
trans-endoxifen | isoform UGT2B7, variant 268Tyr, pH 7.4, 37°C | Homo sapiens | |
0.135 | - |
trans-endoxifen | isoform UGT1A8, variant 173Gly/277Cys, pH 7.4, 37°C | Homo sapiens |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
tamoxifen + UDP-glucuronate | - |
Homo sapiens | UDP + ? | - |
? | |
trans-4-hydroxytamoxifen + UDP-glucuronate | - |
Homo sapiens | UDP + ? | - |
? | |
trans-endoxifen + UDP-glucuronate | - |
Homo sapiens | UDP + ? | - |
? |