First-in-Human Study with Preclinical Data of BCL-2/BCL-xL Inhibitor Pelcitoclax in Locally Advanced or Metastatic Solid Tumors

• Published in: Clinical cancer research Vol. 30; no. 3; pp. 506 - 521
• Main Authors: Lakhani, Nehal J., Rasco, Drew, Wang, Hengbang, Men, Lichuang, Liang, Eric, Fu, Tommy, Collins, Mary C., Min, Ping, Yin, Yan, Davids, Matthew S., Yang, Dajun, Zhai, Yifan
• Format: Journal Article
• Language: English
• Published: United States 01.02.2024
• Subjects: Aniline Compounds; Antineoplastic Agents - adverse effects; Apoptosis; bcl-X Protein - metabolism; Cell Line, Tumor; Humans; Lung Neoplasms - drug therapy; Lymphoma, B-Cell - drug therapy; Myeloid Cell Leukemia Sequence 1 Protein - metabolism; Piperidines; Proto-Oncogene Proteins c-bcl-2; Xenograft Model Antitumor Assays
• ISSN: 1078-0432; 1557-3265; 1557-3265
• DOI: 10.1158/1078-0432.CCR-23-1525

B-cell lymphoma-extra-large (BCL-xL) regulates apoptosis and is an attractive anticancer therapeutic target. However, BCL-xL inhibition also kills mature platelets, hampering clinical development. Using an innovative prodrug strategy, we have developed pelcitoclax (APG-1252), a potent, dual BCL-2 an...