Ko, Sung-Kyun Kim, Jiyeon Na, Deuk Chae Park, Sookil Park, Seong-Hyun Hyun, Ji Young Baek, Kyung-Hwa Kim, Nam Doo Kim, Nak-Kyoon Park, Young Nyun Song, Kiwon Shin, Injae 2024-01-20T07:32:05Z 2024-01-20T07:32:05Z 2021-09-05 2015-03-19 1074-5521 https://pubs.kist.re.kr/handle/201004/125655 The heat shock protein HSP70 plays antiapoptotic and oncogenic roles, and thus its inhibition has been recognized as a potential avenue for anticancer therapy. Here we describe the small molecule, apoptozole (Az), which inhibits the ATPase activity of HSP70 by binding to its ATPase domain and, as a result, induces an array of apoptotic phenotypes in cancer cells. Affinity chromatography provides evidence that Az binds HSP70 but not other types of heat shock proteins including HSP40, HSP60, and HSP90. We also demonstrate that Az induces cancer cell death via caspase-dependent apoptosis by disrupting the interaction of HSP70 with APAF-1. Animal studies indicate that Az treatment retards tumor growth in a xenograft mouse model without affecting mouse viability. These studies suggest that Az will aid the development of new cancer therapies and serve as a chemical probe to gain a better understanding of the diverse functions of HSP70. English CELL PRESS HEAT-SHOCK PROTEINS N-TERMINAL KINASE APAF-1 APOPTOSOME DNA FRAGMENTATION SKELETAL-MUSCLE HEAT-SHOCK-PROTEIN-70 CELLS STRESS BINDING FAMILY A Small Molecule Inhibitor of ATPase Activity of HSP70 Induces Apoptosis and Has Antitumor Activities Article 10.1016/j.chembiol.2015.02.004 1 CHEMISTRY & BIOLOGY, v.22, no.3, pp.391 - 403 CHEMISTRY & BIOLOGY 22 3 391 403 scie scopus 000351714700012 2-s2.0-84925463299 Biochemistry & Molecular Biology Biochemistry & Molecular Biology Article HEAT-SHOCK PROTEINS N-TERMINAL KINASE APAF-1 APOPTOSOME DNA FRAGMENTATION SKELETAL-MUSCLE HEAT-SHOCK-PROTEIN-70 CELLS STRESS BINDING FAMILY