ArticleMolecular pharmacology2009
KU135, a novel novobiocin-derived C-terminal inhibitor of the 90-kDa heat shock protein, exerts potent antiproliferative effects in human leukemic cells.
Article in Molecular pharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 95 citations in OpenAlex.
- Recent progress in the development of HSP90 inhibitors: structure-activity relationship and biological evaluation studies.Molecular diversity · 2026Review
- Breaking the bonds: targeting protein dimerization for prostate cancer therapy.Endocrinology · 2026Review
- The evolution of heat shock protein 90 C-terminal inhibitors: From novobiocin to potential clinical candidates.Cell stress & chaperones · 2026Review
- Investigation of a cryptic ligand binding site on Plasmodium falciparum Hsp90.Bioorganic & medicinal chemistry · 2025Article
- A Coumarin-Imidazothiadiazole Derivative, SP11 Abrogates Tumor Growth by Targeting HSP90 and Its Client Proteins.Molecules (Basel, Switzerland) · 2023Article
- HSP90 inhibitors and cancer: Prospects for use in targeted therapies (Review).Oncology reports · 2023Review
- Heterocyclic Compounds as Hsp90 Inhibitors: A Perspective on Anticancer Applications.Pharmaceutics · 2022Review
- Synthesis and evaluation of 3'- and 4'-substituted cyclohexyl noviomimetics that modulate mitochondrial respiration.Bioorganic & medicinal chemistry · 2022Article
- Article
- Chaperoning STAT3/5 by Heat Shock Proteins: Interest of Their Targeting in Cancer Therapy.Cancers · 2019Review
- Mitochondrial-targeted Hsp90 C-terminal inhibitors manifest anti-proliferative activity.Bioorganic & medicinal chemistry letters · 2019Article
- The Multiple Roles and Therapeutic Potential of Molecular Chaperones in Prostate Cancer.Cancers · 2019Review
- Stimulation of heat shock protein 90 chaperone function through binding of a novobiocin analog KU-32.The Journal of biological chemistry · 2019Article
- Cancer drug resistance: rationale for drug delivery systems and targeted inhibition of HSP90 family proteins.Cancer drug resistance (Alhambra, Calif.) · 2019Review
- New Opportunities for Targeting the Androgen Receptor in Prostate Cancer.Cold Spring Harbor perspectives in medicine · 2018Review
- Synthesis and evaluation of a ring-constrained Hsp90 C-terminal inhibitor that exhibits neuroprotective activity.Bioorganic & medicinal chemistry letters · 2018Article
- Synthesis and Biological Evaluation of Stilbene Analogues as Hsp90 C-Terminal Inhibitors.ChemMedChem · 2017Article
- Synthesis and Biological Evaluation of Novobiocin Core Analogues as Hsp90 Inhibitors.Chemistry (Weinheim an der Bergstrasse, Germany) · 2016Article
- Endoplasmic Reticulum-resident Heat Shock Protein 90 (HSP90) Isoform Glucose-regulated Protein 94 (GRP94) Regulates Cell Polarity and Cancer Cell Migration by Affecting Intracellular Transport.The Journal of biological chemistry · 2016Article
- Novobiocin Analogues That Inhibit the MAPK Pathway.Journal of medicinal chemistry · 2016Article
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
The 90-kDa heat shock protein (Hsp90) assists in the proper folding of numerous mutated or overexpressed signal transduction proteins that are involved in cancer. Consequently, there is considerable interest in developing chemotherapeutic drugs that specifically disrupt the function of Hsp90. Here, we investigated the extent to which a novel novobiocin-derived C-terminal Hsp90 inhibitor, designated KU135, induced antiproliferative effects in Jurkat T-lymphocytes. The results indicated that KU135 bound directly to Hsp90, caused the degradation of known Hsp90 client proteins, and induced more potent antiproliferative effects than the established N-terminal Hsp90 inhibitor 17-allylamino-demethoxygeldanamycin (17-AAG). Closer examination of the cellular response to KU135 and 17-AAG revealed that only 17-AAG induced a strong up-regulation of Hsp70 and Hsp90. In addition, KU135 caused wild-type cells to undergo G(2)/M arrest, whereas cells treated with 17-AAG accumulated in G(1). Furthermore, KU135 but not 17-AAG was found to be a potent inducer of mitochondria-mediated apoptosis as evidenced, in part, by the fact that cell death was inhibited to a similar extent by Bcl-2/Bcl-x(L) overexpression or the depletion of apoptotic protease-activating factor-1 (Apaf-1). Together, these data suggest that KU135 inhibits cell proliferation by regulating signaling pathways that are mechanistically different from those targeted by 17-AAG and as such represents a novel opportunity for Hsp90 inhibition.
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