Article Figures & Data
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Tables
Data Supplement
- Supplemental Data -
Supplemental Abbreviations
Supplemental Materials and Methods
Supplemental References
Supplemental Figure 1. 1H NMR spectrum of PF-07321332.
Supplemental Figure 2. High-resolution mass spectral data for metabolite M1 (PF-07329265).
Supplementary Figure 3. 1H NMR spectrum of M1 (PF-07329265).
Supplementary Figure 4. Comparison of the 1H13C HSQC of PF-07321332 (panel B) and M1
(PF-07329265) (panel C), 1H NMR spectrum of PF-07329265 at 340 ◦K (panel D), 1D ROE
spectra of PF-07329265 at 340 ◦K, C10 methylene irradiated, 3.32, (panel E), 1D ROE
spectrum of PF-07329265 at 340 ◦K, C9 methyl irradiated, 0.86 (panel F).Supplementary Figure 5. Energy minimized three dimensional structure of metabolite M1 (PF07329265).
Supplemental Figure 6. High-resolution mass spectral data for metabolite M2 (PF-07329266).
Supplementary Figure 7. 1H NMR spectrum of metabolite M2 (PF-07329266).
Supplementary Figure 8. High-resolution mass spectra data for metabolite M3 (PF-07329267).
Supplementary Figure 9. 1H NMR spectrum of metabolite M3 (PF-07329267).
Supplementary Figure 10. 1H13C HSQC NMR spectrum of metabolite M3 (PF-07329267).
Supplemental Figure 11. High-resolution mass spectral data for metabolite M4 (PF-07329268).
Supplemental Figure 12. 1H NMR spectrum of metabolite M4 (PF-07329268).
Supplemental Figure 13. 1H-13C HSQC spectral data for metabolite M4 (PF-07329268).
Supplemental Figure 14. High-resolution mass spectral data for dehydrogenated metabolite m/z 498.
Supplemental Figure 15. Eadie-Hofstee plots for the formation of the primary PF-07321332 metabolites PF-07329265 (M1), PF-07329266 (M2), PF-07329267 (M3), and PF-07329268 (M4) following incubation of PF-07321332 (0.02–200 M) with HLM (0.3 mg/ml).
Supplemental Figure 16. IV and PO single dose PK for PF-07321332 in rats (Panel A) and
monkeys (Panel B).
Supplementary Figure 17. Measurement of absorption spectra of CYP metabolic intermediate
(MI) complexes following incubation of PF-07321332 and positive control troleandomycin with
recombinant human CYP3A4, oxidoreductase, and cytochrome b5 supersomes.Supplemental Table 1. Permeability of PF-07321332 across caco-2 cell monolayers.
Supplemental Table 2. Permeability and efflux ratios of PF-07321332 in MDCKI-MDR1 and
MDCKII-BCRP cells.Supplemental Table 3. Plasma protein binding of PF-07321332.
Supplemental Table 4. IC50 values for the reversible inhibition of major human cytochrome
P450 (CYP) enzyme activities in HLM by PF-07321332.Supplemental Table 5. Kinetic Parameters for the time-, concentration-, and NADPHdependent inhibition of CYP3A4/5 by PF-07321332 in NADPH-fortified HLM.
Supplemental Table 6. EC50, Emax, and gamma (Hill slope) (± standard error (SE)a) for induction of CYP3A4 mRNA and midazolam-1’-hydroxylase activity by PF-07321332 in human hepatocytes.
Supplemental Table 7. IC50 values for the reversible inhibition of major human intestinal,
hepatobiliary, and renal transporters by PF-07321332.Supplemental Table 8. Toxicokinetic parameters for orally administered PF-07321332-MTBE co-solvate in rats and monkeys in a 2-week regulatory toxicology study.
- Supplemental Data -