ArticleClinical cancer research : an official journal of the American Association for Cancer Research2013
A purine scaffold HSP90 inhibitor BIIB021 has selective activity against KSHV-associated primary effusion lymphoma and blocks vFLIP K13-induced NF-κB.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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33 citing papers in PubMed, 51 citations in OpenAlex.
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- Molecular mechanism of anticancer effect of heat shock protein 90 inhibitor BIIB021 in human bladder cancer cell line.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
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- Nm23-H1 induces apoptosis in primary effusion lymphoma cells via inhibition of NF-κB signaling through interaction with oncogenic latent protein vFLIP K13 of Kaposi's sarcoma-associated herpes virus.Cellular oncology (Dordrecht, Netherlands) · 2022Article
- The Chaperone System in Salivary Glands: Hsp90 Prospects for Differential Diagnosis and Treatment of Malignant Tumors.International journal of molecular sciences · 2022Article
- Stress-induced inflammation evoked by immunogenic cell death is blunted by the IRE1α kinase inhibitor KIRA6 through HSP60 targeting.Cell death and differentiation · 2022Article
- Recent Advances in Developing Treatments of Kaposi's Sarcoma Herpesvirus-Related Diseases.Viruses · 2021Review
- A novel thermostable beetle luciferase based cytotoxicity assay.Scientific reports · 2021Article
- Viral Infections: Negative Regulators of Apoptosis and Oncogenic Factors.Biochemistry. Biokhimiia · 2020Review
- Modulation of virus-induced NF-κB signaling by NEMO coiled coil mimics.Nature communications · 2020Article
- Narciclasine, an isocarbostyril alkaloid, has preferential activity against primary effusion lymphoma.Scientific reports · 2020Article
- Identification and Structure-Activity Studies of 1,3-Dibenzyl-2-aryl imidazolidines as Novel Hsp90 Inhibitors.Molecules (Basel, Switzerland) · 2019Article
- Molecular mechanisms of viral oncogenesis in humans.Nature reviews. Microbiology · 2018Review
- Peroxisomes support human herpesvirus 8 latency by stabilizing the viral oncogenic protein vFLIP via the MAVS-TRAF complex.PLoS pathogens · 2018Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
purposeKaposi sarcoma-associated herpes virus (KSHV)-associated primary effusion lymphomas (PEL) have extremely poor prognosis when treated with conventional chemotherapy. KSHV-encoded viral FLICE-inhibitory protein (vFLIP) K13 binds to the IkappaB kinase (IKK) complex to constitutively activate the NF-κB pathway, which has been shown to be essential for the survival and proliferation of PEL cells. The molecular chaperone HSP90 is a component of the IKK complex and is required for its activity. EXPERIMENTAL
designWe have analyzed the effect of HSP90 inhibitors on the survival and proliferation of PEL cells and on the activity of the NF-κB pathway.
resultsWe show that BIIB021, a purine scaffold-based orally administrable HSP90 inhibitor, shows preferential cytotoxicity toward PEL cells as compared with non-PEL cells. The cytotoxic effect of BIIB021 against PEL was associated with induction of cell-cycle arrest and apoptosis. BIIB021 blocked the expression of a number of cellular proteins involved in the regulation of cell cycle and apoptosis. BIIB021 also blocked constitutive NF-κB activity present in PEL cells, in part, by blocking the interaction of vFLIP K13 with the IKK complex subunits. In a xenograft model of PEL, BIIB021 significantly reduced tumor growth.
conclusionBIIB021 blocks constitutive NF-κB activity in PEL and shows preferential antitumor activity against PEL in vitro and in vivo. BIIB021 may be a promising agent for treatment of PEL.
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