Article Figures & Data
Additional Files
Data Supplement
- Supplemental Data -
Supplemental Figure 1 - Proton NMR spectra for VU0652922 (M1)
Supplemental Figure 2 - Extracted ion chromatograms (XIC) obtained from extracts of incubations with VU238 (5 mu-M) in (A) mixed gender human hepatic S9 (2 mg/mL), (B) male rhesus monkey hepatic S9 (2 mg/mL), (C) male mouse hepatic S9 (2 mg/mL), (D) male guinea pig hepatic S9 (2 mg/mL), and (E) male minipig hepatic S9 (2mg/mL) demonstrating formation of M1 and M2 in the presence or absence of the XO inhibitor allopurinol (100 mu-M) or the AO inhibitor hydralazine (50 mu-M)
Supplemental Figure 3 - Extracted ion chromatograms (XIC) obtained from extracts of incubations with VU922 (5 mu-M) in (A) mixed gender human hepatic S9 (2 mg/mL), (B) male rhesus monkey hepatic S9 (2 mg/mL), (C) male mouse hepatic S9 (2 mg/mL), (D) male guinea pig hepatic S9 (2 mg/mL), and (E) male minipig hepatic S9 (2mg/mL) demonstrating formation of M2 in the presence or absence of the XO inhibitor allopurinol (100 mu-M) or the AO inhibitor hydralazine (50 mu-M)
Supplemental Figure 4 - Extracted ion chromatograms (XIC) obtained from extracts of incubations with BIBX1382 (5 mu-M) in (A) mixed gender human hepatic S9 (2 mg/mL), (B) male rhesus monkey hepatic S9 (2 mg/mL), (C) male mouse hepatic S9 (2 mg/mL), (D) male guinea pig hepatic S9 (2 mg/mL), and (E) male minipig hepatic S9 (2mg/mL) demonstrating formation of M1b and M2b in the presence or absence of the XO inhibitor allopurinol (100 mu-M) or the AO inhibitor hydralazine (50 mu-M)
Supplemental Table 1 - Percent total MS peak area of parent drug and metabolites from biotransformation experiments with VU238, VU922, or BIBX1382 (5 mu-M) in hepatic S9 of multiple species (2 mg/mL) in the presence or absence of the XO inhibitor allopurinol (100 mu-M) or the AO inhibitor hydralazine (50 mu-M)
Supplemental Figure 5 - UV chromatograms obtained from extracts of 60-minute incubations with 6-thioxanthine (6-TX, 20 mu-M) in (A) male cynomolgus monkey hepatic S9 (2 mg/mL), (B) male rat hepatic S9 (2 mg/mL), (C) mixed gender human hepatic S9 (2 mg/mL), (D) male rhesus monkey hepatic S9 (2 mg/mL), (E) male mouse hepatic S9 (2mg/mL), (F) male guinea pig hepatic S9 (2mg/mL), and (G) male minipig hepatic S9 (2mg/mL) demonstrating formation of 6-thiouric acid (6-TUA) in the presence or absence of the XO inhibitor allopurinol (100 mu-M) or the AO inhibitor hydralazine (50 mu-M)
Supplemental Table 2 - Percent total UV peak area of parent drug (6-TX) and metabolite (6-TUA) from biotransformation experiments (Supplemental Figure 5) with 6-TX (20 mu-M) in hepatic S9 of multiple species (2 mg/mL) in the presence or absence of the XO inhibitor allopurinol (100 mu-M) or the AO inhibitor hydralazine (50 mu-M). 6-TX, 6-thioxanthine; 6-TUA, 6-thiouric acid
- Supplemental Data -