scholarly journals Heat Shock Protein 90 (Hsp90)-Inhibitor-Luminespib-Loaded-Protein-Based Nanoformulation for Cancer Therapy

Polymers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 1798
Author(s):  
Ankit K. Rochani ◽  
Sivakumar Balasubramanian ◽  
Aswathy Ravindran Girija ◽  
Toru Maekawa ◽  
Gagan Kaushal ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Heat Shock ◽  
Cancer Therapy ◽  
Heat Shock Protein ◽  
Heat Shock Protein 90 ◽  
Hsp90 Inhibitor ◽  
Hsp90 Inhibitors ◽  
Delivery Platform ◽  
New Generation

Drugs targeting heat shock protein 90 (Hsp90) have been extensively explored for their anticancer potential in advanced clinical trials. Nanoformulations have been an important drug delivery platform for the anticancer molecules like Hsp90 inhibitors. It has been reported that bovine serum albumin (BSA) nanoparticles (NPs) serve as carriers for anticancer drugs, which have been extensively explored for their therapeutic efficacy against cancers. Luminespib (also known as NVP-AUY922) is a new generation Hsp90 inhibitor that was introduced recently. It is one of the most studied Hsp90 inhibitors for a variety of cancers in Phase I and II clinical trials and is similar to its predecessors such as the ansamycin class of molecules. To our knowledge, nanoformulations for luminespib remain unexplored for their anticancer potential. In the present study, we developed aqueous dispensable BSA NPs for controlled delivery of luminespib. The luminespib-loaded BSA NPs were characterized by SEM, TEM, FTIR, XPS, UV-visible spectroscopy and fluorescence spectroscopy. The results suggest that luminespib interacts by non-covalent reversible interactions with BSA to form drug-loaded BSA NPs (DNPs). Our in vitro evaluations suggest that DNP-based aqueous nanoformulations can be used in both pancreatic (MIA PaCa-2) and breast (MCF-7) cancer therapy.

scholarly journals Kajian Heat Shock Protein 90 (HSP90) dalam Pencarian Kandidat Penghambatnya melalui Ekplorasi Bahan Alam Indonesia

2019 ◽  
Vol 5 (1) ◽  
pp. 1-11
Author(s):  
Rehmadanta Sitepu
Keyword(s):  
Clinical Trials ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Tyrosine Kinases ◽  
Glucocorticoid Receptors ◽  
Heat Shock Protein 90 ◽  
Hsp90 Inhibitor ◽  
Hsp90 Inhibitors ◽  
Protein Activity ◽  
Third Phase

Exploration on anticancer candidates on inhibition of Heat Shock Protein (HSP) activity are increasing in the past ten years. Some of HSP90 inhibitor candidates were in third phase of clinical trials. However, this issue is not followed by the emergency of HSP90 inhibitor research in Indonesia, not only study on natural source but also on synthetic candidates. This study aims to look the development of tracking HSP90 inhibitor candidates globally so that it can initiate the related research in Indonesia. Study of HSP90 and its inhibitors were taken from scientific articles in the range from 2009 to 2018. HSP90 and its inhibitors have important values in the dynamics of functions and stability of proteins to maintain survival of cells. This also include the oncogene proteins that involve in cell proliferation such as tyrosine kinases, transcription factors, and regulatory proteins that expression and interaction depend on HSP90. Expression of the transcription factor p53, Alk gene, Wnt gene, glucocorticoid receptors have also links with HSP90 protein activity. Some candidates for inhibitor of HSP90 have been entering clinical trials such as geldanamycin analogues, resorcinol derivatives, and purines analog. Candidates from natural sources that are also being developed such as luteolin, licochalcone A, oleochantal, novobiocin, epigallocathecin gallat, silybin, deguelin, and celastrol from terpenoid class, Apigenin from flavon class, Curcumin, and  Gambogat Acid. HSP90 inhibitors which are entering the third phase of clinical trial are ganetespib from the resorcinol derivative and retaspimycin from geldanamisin analog group. Exploration of HSP90 inhibitors from Indonesia natural resources still have great potential to be developed because they have high impact values as anticancer candidates.

Abstract: P678 HEAT SHOCK PROTEIN 90 (HSP90) INHIBITORS ATTENUATE INFLAMATORY RESPONSES IN VITRO AND IN VIVO

2009 ◽  
Vol 10 (2) ◽  
pp. e864
Author(s):  
J Madrigal-Matute ◽  
ó López-Franco ◽  
L Blanco-Colio ◽  
B Muñoz-Garcia ◽  
P Ramos-Mozo ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 90 ◽  
Hsp90 Inhibitors

scholarly journals Binding of Natural and Synthetic Inhibitors to Human Heat Shock Protein 90 and Their Clinical Application

Medicina ◽  
2011 ◽  
Vol 47 (8) ◽  
pp. 413 ◽  
Author(s):  
Vilma Petrikaitė ◽  
Daumantas Matulis
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Cancer Progression ◽  
Heat Shock Protein 90 ◽  
Hsp90 Inhibitor ◽  
Titration Calorimetry ◽  
Binding Assays ◽  
Hsp90 Inhibitors ◽  
Lead Compounds ◽  
Binding Energetics

This review describes the recent progress in the field of heat shock protein 90 (Hsp90) inhibitor design. Hsp90 is a heat shock protein with a molecular weight of approximately 90 kDa. Hsp90 is considered a good anticancer target because its inhibition leads to inactivation of its numerous client proteins participating in various signaling and other processes involved in cancer progression. Numerous Hsp90 inhibitors-leads currently tested in clinical trials are presented in this review. Furthermore, this review emphasizes the application of biophysical binding assays in the development of Hsp90 inhibitors. The binding of designed lead compounds to various Hsp90 constructs is measured by isothermal titration calorimetry and thermal shift assay. These assays provide a detailed energetic insight of the binding reaction, including the enthalpy, entropy, heat capacity, and the Gibbs free energy. A detailed description of the binding energetics helps to extend our knowledge of structure-activity relationships in the design of more potent inhibitors. The most active compounds are then tested for their absorption, distribution, metabolism, elimination, toxicity, and activity against cancer cell lines.

Heat-shock protein 90 inhibition in autoimmunity to type VII collagen: evidence that nonmalignant plasma cells are not therapeutic targets

Blood ◽  
2011 ◽  
Vol 117 (23) ◽  
pp. 6135-6142 ◽  
Author(s):  
Michael Kasperkiewicz ◽  
Ralf Müller ◽  
Rudolf Manz ◽  
Moritz Magens ◽  
Christoph M. Hammers ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Plasma Cells ◽  
Protein Biosynthesis ◽  
Heat Shock Protein 90 ◽  
Hsp90 Inhibitors ◽  
Hsp90 Inhibition ◽  
Type Vii Collagen

Abstract Blocking heat-shock protein 90 (Hsp90) induces death of malignant plasma cells by activation of the unfolded protein response, a signaling pathway activated by accumulation of misfolded proteins within the endoplasmic reticulum. We hypothesized that nontransformed plasma cells are also hypersensitive to Hsp90 inhibition because of their high amount of protein biosynthesis. To investigate this hypothesis, 2 different Hsp90 inhibitors, the geldanamycin derivative 17-DMAG and the nontoxic peptide derivative TCBL-145, were applied to mice with experimental epidermolysis bullosa acquisita, an autoimmune bullous disease characterized by autoantibodies against type VII collagen of the dermal-epidermal junction. Both inhibitors ameliorated clinical disease of type VII collagen–immunized mice, suppressed auto-antibody production, and reduced dermal neutrophilic infiltrate. Interestingly, total plasma cell numbers, type VII collagen–specific plasma cells, and germinal center B cells were unaffected by anti-Hsp90 treatment in vivo. However, T-cell proliferation was potently inhibited, as evidenced by the reduced response of isolated lymph node cells from immunized mice to in vitro restimulation with anti-CD3/CD28 antibody or autoantigen in the presence of Hsp90 inhibitors. Our results suggest that Hsp90 blockade has no impact on normal or autoreactive plasma cells in vivo and indentify T cells as targets of anti-Hsp90 treatment in autoimmunity to type VII collagen.

scholarly journals In VitroActivity of Geldanamycin Derivatives againstSchistosoma japonicumandBrugia malayi

2010 ◽  
Vol 2010 ◽  
pp. 1-7 ◽  
Author(s):  
David Wenkert ◽  
Bernadette Ramirez ◽  
Yuehai Shen ◽  
Michael A. Kron
Keyword(s):  
Clinical Trials ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Heat Shock Protein 90 ◽  
Shock Proteins ◽  
Work Supports ◽  
Antiparasitic Agents

Geldanamycin (GA) is a benzoquinone-containing ansamycin that inhibits heat shock protein 90. GA derivatives are being evaluated as anti-neoplastic agents, but their utility against parasites whose heat shock proteins (Hsps) have homology with human Hsp90 is unknown. The activities of four synthetic GA derivatives were testedin vitrousing adultBrugia malayiandSchistosoma japonicum. Two of the derivatives, 17-N-allyl-17-demethoxygeldanamycin (17-AAG) and 17-N-(2-dimethylaminoethylamino)-17-demethoxygeldanamycin (DMAG), are currently in human clinical trials as anticancer drugs. Using concentrations considered safe peak plasma concentrations for these two derivatives, all four derivatives were active against both parasites. The less toxic derivative 17-AAG was as effective as GA in killingS. japonicum, and both DMAG and 5′-bromogeldanoxazinone were more active than 17-AAG againstB. malayi. This work supports continued evaluation of ansamycin derivatives as broad spectrum antiparasitic agents.

scholarly journals The Effect of Heat Shock Protein 90 Inhibitor on Pain in Cancer Patients: A Systematic Review and Meta-Analysis

Medicina ◽  
2020 ◽  
Vol 57 (1) ◽  
pp. 5
Author(s):  
Victoria N. Miles ◽  
Roma K. Patel ◽  
Amanda G. Smith ◽  
Ryan P. McCall ◽  
Jun Wu ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Abdominal Pain ◽  
Back Pain ◽  
Heat Shock ◽  
Meta Analysis ◽  
Heat Shock Protein 90 ◽  
Hsp90 Inhibitor ◽  
Controlled Trials ◽  
Hsp90 Inhibitors ◽  
Randomized Controlled

Heat shock protein 90 (Hsp90) is a molecular chaperone that plays an essential role in tumor growth. Numerous Hsp90 inhibitors have been discovered and tested in preclinical and clinical trials. Recently, several preclinical studies have demonstrated that Hsp90 inhibitors could modulate pain sensitization. However, no studies have evaluated the impact of Hsp90 inhibitors on pain in the patients. This study aims to summarize the pain events reported in clinical trials assessing Hsp90 inhibitors and to determine the effect of Hsp90 inhibitors on pain in patients. We searched PubMed, EBSCOhost, and clinicaltrials.gov for Hsp90 inhibitor clinical trials. The pain-related adverse events were summarized. Meta-analysis was performed using the data reported in randomized controlled trials. We identified 90 clinical trials that reported pain as an adverse effect, including 5 randomized controlled trials. The most common types of pain reported in all trials included headache, abdominal pain, and back pain. The meta-analysis showed that Hsp90 inhibitors increased the risk of abdominal pain significantly and appeared to increase the risk for back pain. In conclusion, Hsp90 inhibitor treatment could potentially increase the risk of pain. However, the meta-analysis demonstrated only moderate evidence for the connection between Hsp90 inhibitor and pain.

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