Lenacapavir Exhibits Atropisomerism - Mechanistic Pharmacokinetics and Disposition Studies of Lenacapavir Reveal Intestinal Excretion as a Major Clearance Pathway

Data Supplement

• Supplemental Data -

  Supplemental Methods. Additional details provided including lenacapavir (LEN) structure with sites of radiolabel, experimental methods, cumulative radioactivity excretion graphs, and summary data/structures of LEN biotransformation products.
  

  Figure S1. Chemical structure of lenacapavir (LEN), [¹⁴C]LEN and [³H]LEN.
  

  Table S1. Bi-directional permeability of LEN in human MDR1 (P-gp-) and BCRP-transfected MDCK cells.
  

  Table S2. Uptake rates for LEN and control compounds in non-transfected CHO cells (WT) and transfected CHO cells without and with rifampicin.
  

  Table S3. LC-HRMS conditions (Method 1 used for rat profiling).
  

  Table S4. LC-HRMS conditions (Methods 2 and 3 used for rat and dog profiling).
  

  Table S5. Summary of representative liquid chromatography-high resolution mass spectrometry data for LEN and its biotransformation products.
  

  Figure S2. Summary of late-eluting LEN-derived product peaks formed due to radiolysis/photolysis.
  

  Figure S3. Concentration-time profile of total radioactivity in blood and plasma.
  

  Figure S4. Concentration-time profiles of total radioactivity in blood, plasma, and excreta.