Supplementary Data from Expanding the Repertoire for 'Large Small Molecules': Prodrug ABBV-167 Efficiently Converts to Venetoclax with Reduced Food Effect in Healthy Volunteers

Autor: Andrew J. Souers, Nathaniel D. Catron, Geoff G.Z. Zhang, Xilu Wang, Ahmed A. Suleiman, Deanne Stolarik, Yi Shi, Ahmad Y. Sheikh, Yeshwant D. Sanzgiri, Saul H. Rosenberg, Yu-Ming Pu, Darren C. Phillips, Chang H. Park, Rajeev M. Menon, Kennan C. Marsh, Richard A. Marks, Joel D. Leverson, Yi-Yin Ku, Russell C. Klix, John C. Kalvass, Russell A. Judge, Jianguo Ji, Gary J. Jenkins, Richard Hong, Kaid C. Harper, Keith M. Fournier, Steven W. Elmore, Rohinton Edalji, Shuang Chen, Jie Chen, Orlando F. Bueno, Zhi-Fu Tao, Ahmed Hamed Salem
Rok vydání: 2023
Popis: 1. Measured pKa values of ABBV-167 (Table S1. Ionization constants of ABBV-167) 2. Preparation of ABBV-167 on large scale (Scheme S1: Synopsis of GMP synthesis of ABBV-167) 3. Preparation of clinical ABBV-167 drug supply 4. Animal pharmacokinetics (Table S2. Single dose pharmacokinetics of prodrug 3 and parent venetoclax in mouse and dog after IV dosing of prodrug 3. Table S3. Single dose pharmacokinetics of 3 after oral dosing in mouse and dog. Table S4. Single dose pharmacokinetics of parent venetoclax in mouse and dog after oral dosing of 3.) 5. Clinical study (Study design, Pharmacokinetic and statistical analysis, Safety and tolerability assessments, Clinical pharmacokinetic results, Table S5. Effect of prodrug and food on venetoclax bioavailability, Safety results) 6. Crystallography methods (Protein preparation. BCL-2 ABBV-167 complex crystallization. X-ray structure determination. Table S6. Diffraction data collection and refinement statistics for BCL-2 in complex with ABBV-167 (PDB code 7LHB))
Databáze: OpenAIRE