Search results for "HSP90 inhibitor"

The HSP90 inhibitor, 17AAG, protects the intestinal stem cell niche and inhibits graft versus host disease development.

2016

IF 7.932; International audience; Graft versus host disease (GvHD), which is the primary complication of allogeneic bone marrow transplantation, can alter the intestinal barrier targeted by activated donor T-cells. Chemical inhibition of the stress protein HSP90 was demonstrated in vitro to inhibit T-cell activation and to modulate endoplasmic reticulum (ER) stress to which intestinal cells are highly susceptible. Since the HSP90 inhibitor 17-allylamino-demethoxygeldanamycin (17AAG) is developed in clinics, we explored here its ability to control intestinal acute GvHD in vivo in two mouse GvHD models (C57BL/6 -> BALB/c and FVB/N -> Lgr5-eGFP), ex vivo in intestine organoids and in vitro in …

Identification of the plant compound geraniin as a novel Hsp90 inhibitor

2013

Besides its function in normal cellular growth, the molecular chaperone heat shock protein 90 (Hsp90) binds to a large number of client proteins required for promoting cancer cell growth and/or survival. In an effort to discover new small molecules able to inhibit the Hsp90 ATPase and chaperoning activities, we screened, by a surface plasmon resonance assay, a small library including different plant polyphenols. The ellagitannin geraniin, was identified as the most promising molecule, showing a binding affinity to Hsp90α similar to that of 17-(allylamino)-17-demethoxygeldanamycin (17AGG). Geraniin was able to inhibit in vitro the Hsp90α ATPase activity in a dose−dependent manner, with an in…

Identificazione e sintesi di nuovi potenziali inibitori di Heat Shock Protein 90

2008

BINDING MODES OF HSP90 INHIBITORS INVESTIGATED THROUGH INDUCED FIT DOCKING: IMPORTANCE OF ACTIVE SITE FLEXIBILITY

2008

A randomized phase II study of ganetespib, a heat shock protein 90 inhibitor, in combination with docetaxel in second-line therapy of advanced non-sm…

2015

Background: This trial was designed to evaluate the activity and safety of ganetespib in combination with docetaxel in advanced non-small cell lung cancer (NSCLC) and to identify patient populations most likely to benefit from the combination. Patients and methods: Patients with one prior systemic therapy for advanced disease were eligible. Docetaxel (75 mg/m<sup>2</sup> on day 1) was administered alone or with ganetespib (150 mg/m<sup>2</sup> on days 1 and 15) every 3 weeks. The primary end points were progression-free survival (PFS) in two subgroups of the adenocarcinoma population: patients with elevated lactate dehydrogenase (eLDH) and mutated KRAS (mKRAS). Resul…

Inside the Hsp90 inhibitors binding mode through induced fit docking

2009

Abstract During the last few decades, the development of new anticancer strategies had to face the instability of many tumors, occurring when the genetic plasticity of cells produces new drug-resistant cancers. It has been shown that a chaperone protein, heat shock protein 90 (Hsp90), is one of the fundamental factors involved in the cell response to stresses, and its role in many biochemical pathways has been demonstrated. Thus, the inhibition of Hsp90 represents a new target of antitumor therapy, since it may influence many specific signaling pathways. The natural antibiotic Geldanamycin is the first Hsp90 inhibitor that has been identified. Nevertheless, more potent and water-soluble sma…

Design, synthesis, and biological evaluation of pyridothienotriazolopyrimidine derivatives as new HSP90 inhibitors

2010

Rôle des protéines de choc thermique dans la régulation du facteur de transcription HIF

2011

Both HIF1α and HIF2α proteins are highly involved in the development of pathologies, such as cancers, which are prime public health issues. These proteins are primarily controlled at the protein level by ubiquitin-dependant degradation, and regulate numerous cellular processes which are likely to favor the development of these diseases. A recent issue in therapeutic research is to identify partners that might regulate the expression and the activity of the HIFα proteins, with the aim to elaborate targeted therapies. Heat shock proteins (HSPs) form a family of proteins whose main function is to regulate protein homeostasis in cells, which they achieve through interaction with the ubiquitin-p…

The Major Heat Shock Proteins, Hsp70 and Hsp90, in 2-Methoxyestradiol-Mediated Osteosarcoma Cell Death Model

2020

2-Methoxyestradiol is one of the natural 17&beta