Article Figures & Data
Additional Files
Data Supplement
- Supplemental Data -
Supplementary Material
Supplementary Table 1 - Capmatinib and metabolites in plasma (mean of n=6, SD)
Supplementary Table 2 - Capmatinib and metabolites in excreta (means of n=6, SD)
Supplementary Table 3A - Mass spectral data of [14C]capmatinib and metabolites observed in the study.
Supplementary Table 3B - Exact mass measurements and hydrogen/deuterium exchange.
Supplementary Figure 1 - Plasma metabolite profiles and kinetics of [14C]capmatinib in rats after oral administration.
Supplementary Methods
Supplementary Results
Supplementary Table 4A - Concentration-dependent biotransformation of [14C] Capmatinib to M16.
Supplementary Table 4B - Concentration-dependent biotransformation of [14C] Capmatinib to M19.
Supplementary Table 5 - Estimation of enzyme kinetics constants.
Supplementary Table 6A - Phenotyping with molybdenum hydroxylases for the formation of M16.
Supplementary Table 6B - Phenotyping with molybdenum hydroxylases for the formation of M19.
Supplementary Figure 2 - Effect of chemical inhibitors on capmatinib metabolism in HLC (M19 formation).
Supplementary Figure 3 - Incubations of O6-Benzylguanine with human hepatocytes in the absence and presence of 18O-water.
Supplementary Figure 4 - Incubation of [14C] capmatinib with human hepatocytes in the absence and presence of 18O-water.
Supplementary Table 7 - Summary of 18O incorporation into metabolites of capmatinib and the positive control O6-benzylguanine in incubations with Hμrel® human pooled primary hepatic co-culture and human hepatocytes.
Supplementary Figure 5 - Proposed metabolic pathway of capmatinib.
Supplementary Table 8 - Species comparison of metabolites.
Supplementary Table 9 - Enzyme kinetics
Supplementary Figure 6 - Biotransformation with recombinant CYP450s and FMOs.
Supplementary Table 10 - 10 Enzyme kinetics
Supplementary Table 11 - Chemical Inhibition
Supplementary Figure 7 - Effect of CYP-selective inhibitors on capmatinib total metabolism in HLM.
Supplementary Table 12 - Correlation analysis of capmatinib total metabolism rates with marker enzyme activities.
Supplementary Figure 8 - Correlation of [14C]capmatinib metabolism rates with CYP3A4/5 marker enzyme activities (testosterone 6beta-hydroxylation).
Supplementary Figure 9 - Schematic presentation of the synthesis of the M13 (2) and M19 (5).
Supplementary Metabolite - M3, M8, M13, M16, M17, M18, M19, M21
Supplementary References
- Supplemental Data -