Data Supplement

• Supplemental Data -

  Supplemental Methods

  Supplemental Table S1. LC-MS/MS Conditions for Metabolite Profiling and 14C-Abrocitinib Quantitation.

  Supplemental Table S2. LC-MS/MS Conditions for Isolation of Metabolites M6 and M7 - Initial Assessment.

  Supplemental Table S3. LC-MS/MS Conditions for Isolation of Metabolites M6 and M7 - Initial Fractionation.

  Supplemental Table S4. LC-MS/MS Conditions for Isolation of Metabolites M6 and M7 - Analysis of Fractions.

  Supplemental Table S5. LC-MS/MS Conditions for Isolation of Metabolites M6 and M7 – Final Fractionation.

  Supplemental Table S6. LC-MS/MS Conditions for Abrocitinib in Plasma.

  Supplemental Table S7. LC-MS/MS Conditions for In Vitro Hepatocyte Fractional Metabolism

  Supplemental Table S8. LC-MS/MS conditions for in vitro CYP450 assignment (Enzyme kinetics and chemical inhibition)

  Supplemental Table S9. LC-MS/MS conditions for abrocitinib in plasma protein binding and blood-to-plasma ratio studies.

  Supplemental Table S10. LC-MS/MS conditions for M1 in plasma protein binding and blood-to-plasma ratio studies.

  Supplemental Table S11. LC-MS/MS conditions for M2 in plasma protein binding and blood-to-plasma ratio studies.

  Supplemental Table S12. Incidence of treatment-emergent mild adverse events.

  Supplemental Table S13. Diagnostic MS product ions used for abrocitinib and proposed metabolite structures.

  Supplemental Figure S1. 1H13C HMBC spectrum (left) and 1H1H COSY spectrum (right) of M6 (PF-07095462, 370, m/z 370) metabolite isolated from pooled human urine.

  Supplemental Figure S2. 1H13C HMBC spectrum (left) and 1H1H COSY spectrum (right) of M7 (PF-06737821, 354-1, m/z 354) metabolite isolated from pooled human urine.

  Supplemental Figure S3. Radiochromatogram following 30-minute incubation of 1 µM 14C-abroctinib (PF04965842) in human hepatocytes (0.75 million cells/mL)

  Supplemental Figure S4. Enzyme kinetic plots for primary metabolites M1 (A), M2/M3 (B), M4 (C), and 149 (D) and secondary metabolites M7 (E), 358-1 (F), and 372-1 (G) from abrocitinib metabolism.