Discovery and Canine Preclinical Assessment of a Nontoxic Procaspase-3–Activating Compound

• Published in: Cancer research (Chicago, Ill.) Vol. 70; no. 18; pp. 7232 - 7241
• Main Authors: Peterson, Quinn P., Hsu, Danny C., Novotny, Chris J., West, Diana C., Kim, Dewey, Schmit, Joanna M., Dirikolu, Levent, Hergenrother, Paul J., Fan, Timothy M.
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.09.2010
• Subjects: Animals; Antineoplastic agents; Apoptosis - drug effects; Biological and medical sciences; Caspase 3 - metabolism; Dog Diseases - drug therapy; Dog Diseases - enzymology; Dog Diseases - pathology; Dogs; Enzyme Activation - drug effects; HeLa Cells; Humans; Hydrazones - pharmacokinetics; Hydrazones - pharmacology; Hydrazones - toxicity; Jurkat Cells; Lymphoma, B-Cell - drug therapy; Lymphoma, B-Cell - enzymology; Lymphoma, B-Cell - pathology; Lymphoma, B-Cell - veterinary; Male; Medical sciences; Mice; Mice, Inbred C57BL; Pharmacology. Drug treatments; Piperazines - pharmacokinetics; Piperazines - pharmacology; Piperazines - toxicity; Tumors; U937 Cells; Fissipedia; Evaluation; Carnivora; Vertebrata; Mammalia; Animal; Preclinical trial; Dog

A critical event in the apoptotic cascade is the proteolytic activation of procaspases to active caspases. The caspase autoactivating compound PAC-1 induces cancer cell apoptosis and exhibits antitumor activity in murine xenograft models when administered orally as a lipid-based formulation or impla...