Preclinical efficacy of PF-04942847, a novel HSP90 inhibitor, in osteosarcoma

2014 ◽  
Author(s):  
Francois Lamoureux ◽  
Marc Baud'Huin ◽  
Benjamin Ory ◽  
Dominique Heymann ◽  
Francoise Redini
Keyword(s):  
Hsp90 Inhibitor ◽  
Preclinical Efficacy

Abstract 1964: Preclinical efficacy of the HSP90 inhibitor SNX-5422 in targeting C481S mutant BTK and ibrutinib resistant CLL

2018 ◽  
Author(s):  
Timothy L. Chen ◽  
Bonnie Harrington ◽  
Jean Truxall ◽  
Ronni Wasmuth ◽  
Amy Lehman ◽  
...  
Keyword(s):  
Hsp90 Inhibitor ◽  
Preclinical Efficacy

Demonstrating preclinical efficacy of AUY922, a novel Hsp90 inhibitor, alone and in combination with standard chemotherapy or radiation in esophageal adenocarcinoma.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. e13506-e13506
Author(s):  
Juliann Kosovec ◽  
Christina Rotoloni ◽  
Ali H Zaidi ◽  
Yoshihiro Komastu ◽  
Lori Kelly ◽  
...  
Keyword(s):  
Esophageal Adenocarcinoma ◽  
Hsp90 Inhibitor ◽  
Standard Chemotherapy ◽  
Preclinical Efficacy

Preclinical efficacy of STA-12-8666, an HSP90 inhibitor-targeted SN-38 conjugate, in small cell lung cancer (SCLC).

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. e18560-e18560
Author(s):  
Yanis Boumber ◽  
Anna Gaponova ◽  
Anna S Nikonova ◽  
Alexander Deneka ◽  
Alexander Kudinov ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Hsp90 Inhibitor ◽  
Small Cell ◽  
Small Cell Lung ◽  
Preclinical Efficacy

New models of breast and lung cancer bone metastases for preclinical efficacy testing

2016 ◽  
Author(s):  
Mari I. Suominen ◽  
Urs B. Hagemann ◽  
Yvonne Konkol ◽  
Jenni Bernoulli ◽  
Katja M. Fagerlund ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Bone Metastases ◽  
New Models ◽  
Preclinical Efficacy

Effect of HSP90 inhibitor radicicol on zebrafish embryonic development

2017 ◽  
Vol 24 (5) ◽  
pp. 988
Author(s):  
Juntao LUO ◽  
Yan LI ◽  
Xiaofan TAO ◽  
Wei LIU ◽  
Guojun NI ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Hsp90 Inhibitor

BIIB021, a novel Hsp90 inhibitor, sensitizes esophageal squamous cell carcinoma to radiation

2014 ◽  
Vol 452 (4) ◽  
pp. 945-950 ◽  
Author(s):  
Xin-Tong Wang ◽  
Ci-Hang Bao ◽  
Yi-Bin Jia ◽  
Nana Wang ◽  
Wei Ma ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Hsp90 Inhibitor

scholarly journals HSP90-dependent PUS7 overexpression facilitates the metastasis of colorectal cancer cells by regulating LASP1 abundance

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Dan Song ◽  
Ming Guo ◽  
Shuai Xu ◽  
Xiaotian Song ◽  
Bin Bai ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Intellectual Development ◽  
Molecular Mechanisms ◽  
Hsp90 Inhibitor ◽  
Pseudouridine Synthase ◽  
Novel Approach ◽  
Cell Metastasis ◽  
Underlying Mechanisms

Abstract Background Pseudouridine synthase (PUS) 7 is a member of the PUS family that catalyses pseudouridine formation. It has been shown to be involved in intellectual development and haematological malignancies. Nevertheless, the role and the underlying molecular mechanisms of PUS7 in solid tumours, such as colorectal cancer (CRC), remain unexplored. This study elucidated, for the first time, the role of PUS7 in CRC cell metastasis and the underlying mechanisms. Methods We conducted immunohistochemistry, qPCR, and western blotting to quantify the expression of PUS7 in CRC tissues as well as cell lines. Besides, diverse in vivo and in vitro functional tests were employed to establish the function of PUS7 in CRC. RNA-seq and proteome profiling analysis were also applied to identify the targets of PUS7. PUS7-interacting proteins were further uncovered using immunoprecipitation and mass spectrometry. Results Overexpression of PUS7 was observed in CRC tissues and was linked to advanced clinical stages and shorter overall survival. PUS7 silencing effectively repressed CRC cell metastasis, while its upregulation promoted metastasis, independently of the PUS7 catalytic activity. LASP1 was identified as a downstream effector of PUS7. Forced LASP1 expression abolished the metastasis suppression triggered by PUS7 silencing. Furthermore, HSP90 was identified as a client protein of PUS7, associated with the increased PUS7 abundance in CRC. NMS-E973, a specific HSP90 inhibitor, also showed higher anti-metastatic activity when combined with PUS7 repression. Importantly, in line with these results, in human CRC tissues, the expression of PUS7 was positively linked to the expression of HSP90 and LASP1, and patients co-expressing HSP90/PUS7/LASP1 showed a worse prognosis. Conclusions The HSP90-dependent PUS7 upregulation promotes CRC cell metastasis via the regulation of LASP1. Thus, targeting the HSP90/PUS7/LASP1 axis may be a novel approach for the treatment of CRC.

scholarly journals Elucidation of the Molecular Pathways Involved in the Protective Effects of AUY-922 in LPS-Induced Inflammation in Mouse Lungs

2021 ◽  
Vol 14 (6) ◽  
pp. 522
Author(s):  
Mohammad S. Akhter ◽  
Mohammad A. Uddin ◽  
Khadeja-Tul Kubra ◽  
Nektarios Barabutis
Keyword(s):  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Intratracheal Instillation ◽  
Hsp90 Inhibitor ◽  
Molecular Pathways ◽  
Protective Effects ◽  
Inflammatory Pathways ◽  
Cytokines And Chemokines ◽  
The Unfolded Protein Response ◽  
Mouse Lungs

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) cause thousands of deaths every year and are associated with high mortality rates (~40%) due to the lack of efficient therapies. Understanding the molecular mechanisms associated with those diseases will most probably lead to novel therapeutics. In the present study, we investigated the effects of the Hsp90 inhibitor AUY-922 in the major inflammatory pathways of mouse lungs. Mice were treated with LPS (1.6 mg/kg) via intratracheal instillation for 24 h and were then post-treated intraperitoneally with AUY-922 (10 mg/kg). The animals were examined 48 h after AUY-922 injection. LPS activated the TLR4-mediated signaling pathways, which in turn induced the release of different inflammatory cytokines and chemokines. AUY-922 suppressed the LPS-induced inflammation by inhibiting major pro-inflammatory pathways (e.g., JAK2/STAT3, MAPKs), and downregulated the IL-1β, IL-6, MCP-1 and TNFα. The expression levels of the redox regulator APE1/Ref1, as well as the DNA-damage inducible kinases ATM and ATR, were also increased after LPS treatment. Those effects were counteracted by AUY-922. Interestingly, this Hsp90 inhibitor abolished the LPS-induced pIRE1α suppression, a major component of the unfolded protein response. Our study elucidates the molecular pathways involved in the progression of murine inflammation and supports our efforts on the development of new therapeutics against lung inflammatory diseases and sepsis.

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