Data Supplement

• Supplemental Data -

  Supplemental Table S1. Composition of urine, feces, and bile pools from the rat ADME study.
  

  Supplemental Table S2. Summary of total recovery of radioactivity 0–168 h after a single oral dose of [14C]AZD4831 (40 mg/kg) to intact male and female rats (n = 3/sex).

  Supplemental Table S3. Summary of total recovery of radioactivity 0–168 h after a single intravenous dose of [14C]AZD4831 (10 mg/kg) to intact male and female rats (n = 3/sex).

  Supplemental Table S4. Summary of total recovery of radioactivity 0–72 h after a single oral dose of [14C]AZD4831 (40 mg/kg) to bile-duct cannulated male and female rats (n = 3/sex).

  Supplemental Table S5. Mass-to-charge ratios for fragment ions of AZD4831 and non-cyclic metabolites, acquired using LC-HRMS and MS-MS.

  Supplemental Table S6. Mass-to-charge ratios for fragment ions of AZD4831 and cyclized metabolites, acquired using LC-HRMS and MS-MS.

  Supplemental Table S7. Mass-to-charge ratios for fragment ions of non-cyclic metabolites in samples from rats, acquired using LCHRMS and MS-MS.

  Supplemental Table S8. Quantitative estimates of AZD4831 and metabolites in samples collected after a single intravenous administration of AZD4831 to intact rats at a target dose level of 10 mg/kg (10 MBq/kg).

  Supplemental Table S9. Quantitative estimates (% of dose) of AZD4831 and metabolites in samples collected after a single oral administration of AZD4831 to BDC rats at a target dose level of 40 mg/kg (10 MBq/kg).

  Supplemental Figure S1. Proposed formation of fragment ion k from protonated AZD4831 in positive ionization high-resolution mass spectrometry.

  Supplemental Figure S2. Proposed formation of fragment ion b1 from protonated AZD4831 and metabolites M7, M9 and M11 in positive ionization HR-MS-MS mode.

  Supplemental Figure S3. Fragmentation pathways for protonated AZD4831: multiple fragmentation pathways leading to the diagnostic ion m/z 318.0468 (b) via deamination of AZD4831 at [M+H]+ = 335.0733.

  Supplemental Figure S4. Fragmentation pathways for protonated AZD4831: proposed fragmentation from m/z 318.0468 (b) to 282.0701 (c) and 259.0638 (d).

  Supplemental Figure S5. Fragmentation pathways for protonated AZD4831: proposed formation of m/z 168.0232 (f).

  Supplemental Figure S6. Fragmentation pathways for protonated AZD4831: proposed formation of m/z 151.0315 (g), 116.0626 (i), and 115.0548 (j).

  Supplemental Figure S7. Metabolite profiles of AZD4831 and metabolites in rat urine samples.

  Supplemental Figure S8. Metabolite profiles of AZD4831 and metabolites in rat feces samples.

  Supplemental Figure S9. Metabolite profiles of AZD4831 and metabolites in rat bile samples.

  Supplemental Figure S10. Metabolite profiles of AZD4831 and metabolites in rat plasma samples.