Neutral analogs of the heat shock protein 70 (Hsp70) inhibitor, JG-98
Copyright policy )Neutral analogs of the heat shock protein 70 (Hsp70) inhibitor, JG-98
The heat shock protein 70 (Hsp70) family of molecular chaperones are highly expressed in tumors. Inhibitors containing a pyridinium-modified benzothiazole, such as JG-98, bind to a conserved, allosteric site in Hsp70, showing promising anti-proliferative activity in cancer cells. When bound to Hsp70, the charged pyridinium makes favorable contacts; however, this moiety also increases the inhibitor's fluorescence, giving rise to undesirable interference in biochemical and cell-based assays. Here, we explore whether the pyridinium can be replaced with a neutral pyridine. We report that pyridine-modified benzothiazoles, such as compound 17h (JG2-38), have reduced fluorescence, yet retain promising anti-proliferative activity (EC50 values ~0.1 to 0.07 µM) in breast and prostate cancer cell lines. These chemical probes are expected to be useful in exploring the roles of Hsp70s in tumorigenesis and cell survival.
Aging, Allosteric inhibitor, Medicinal & Biomolecular Chemistry, Anti-cancer agents, Organic chemistry, Antineoplastic Agents, Drug Screening Assays, Fluorescence, Cell Line, Medicinal and Biomolecular Chemistry, Structure-Activity Relationship, Breast cancer, Cell Line, Tumor, Breast Cancer, Medicinal and biomolecular chemistry, Chemical probe, Humans, HSP70 Heat-Shock Proteins, Benzothiazoles, Cancer, Cell Proliferation, Fluorescent Dyes, Tumor, Prostate cancer, Binding Sites, Molecular Structure, Organic Chemistry, Antitumor, Pharmacology and Pharmaceutical Sciences, Molecular Docking Simulation, Chemical Sciences, Molecular chaperone, Proteostasis, Drug Screening Assays, Antitumor, Protein Binding
Aging, Allosteric inhibitor, Medicinal & Biomolecular Chemistry, Anti-cancer agents, Organic chemistry, Antineoplastic Agents, Drug Screening Assays, Fluorescence, Cell Line, Medicinal and Biomolecular Chemistry, Structure-Activity Relationship, Breast cancer, Cell Line, Tumor, Breast Cancer, Medicinal and biomolecular chemistry, Chemical probe, Humans, HSP70 Heat-Shock Proteins, Benzothiazoles, Cancer, Cell Proliferation, Fluorescent Dyes, Tumor, Prostate cancer, Binding Sites, Molecular Structure, Organic Chemistry, Antitumor, Pharmacology and Pharmaceutical Sciences, Molecular Docking Simulation, Chemical Sciences, Molecular chaperone, Proteostasis, Drug Screening Assays, Antitumor, Protein Binding
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