Discovery of Peptidomimetic Antibody–Drug Conjugate Linkers with Enhanced Protease Specificity

• Published in: Journal of medicinal chemistry Vol. 61; no. 3; pp. 989 - 1000
• Main Authors: Wei, BinQing, Gunzner-Toste, Janet, Yao, Hui, Wang, Tao, Wang, Jing, Xu, Zijin, Chen, Jinhua, Wai, John, Nonomiya, Jim, Tsai, Siao Ping, Chuh, Josefa, Kozak, Katherine R, Liu, Yichin, Yu, Shang-Fan, Lau, Jeff, Li, Guangmin, Phillips, Gail D, Leipold, Doug, Kamath, Amrita, Su, Dian, Xu, Keyang, Eigenbrot, Charles, Steinbacher, Stefan, Ohri, Rachana, Raab, Helga, Staben, Leanna R, Zhao, Guiling, Flygare, John A, Pillow, Thomas H, Verma, Vishal, Masterson, Luke A, Howard, Philip W, Safina, Brian
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 08.02.2018; Amer Chemical Soc
• Subjects: Cathepsin B - metabolism; Chemistry, Medicinal; Drug Discovery; Humans; Immunoconjugates - chemistry; Immunoconjugates - metabolism; Intracellular Space - metabolism; Life Sciences & Biomedicine; Peptidomimetics - chemistry; Peptidomimetics - metabolism; Pharmacology & Pharmacy; Science & Technology; Substrate Specificity; ANTICANCER ACTIVITY; ATTACHMENT SITE; POTENT; STABILITY; INHIBITORS; ADCS; NEXT-GENERATION; CANCER-THERAPY; CATHEPSIN-B; STRATEGIES

Antibody–drug conjugates (ADCs) have become an important therapeutic modality for oncology, with three approved by the FDA and over 60 others in clinical trials. Despite the progress, improvements in ADC therapeutic index are desired. Peptide-based ADC linkers that are cleaved by lysosomal proteases...