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Inhibitors of Heat Shock Proteins

Heat shock proteins (HSP) are a class of functionally related proteins involved in the folding and unfolding of other proteins, including oncoproteins. Their expression is increased when cells are exposed to stress. NVP-AUY922, an HSP90 inhibitor, was shown to inhibit proliferation of oral squamous cell carcinoma cell lines. Antitumor activity was mediated by the degradation of client proteins inducing ErbB2, p-Akt, p-S6, HIF1-a and VEGF and increased expression of cleaved caspase-3 and apoptosis (Okui et al. 2011). Suppression of p-Akt and VEGF expression in a xenograft model was also documented after administration of the HSP90 inhibitor (Okui et al. 2011). Another group showed radiosensitization in a human SCCHN xenograft model treated by the same HSP 90 inhibitor (Zaidi et al.

2012). Interaction of HSP90 with EGFR was found to be critical for maintaining receptor stability as well as growth of EGFR-dependent cancer (Ahsan et al. 2012). These findings support the potential role of HSP90 inhibitors for the treatment of SCCHN. An ongoing study is investigating the combination of cetuximab and IPI-926, an HSP inhibitor, in patients with R/M SCCHN (NCT01255800).

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Heat Shock Protein (HSP) Inhibitors
Proteins are involved in nearly every aspect of cellular function, and producing proteins with the correct amino acid sequence is only the first step for a cell. After this, most proteins, which are very large and complex molecules, need to fold into exactly the right three-dimensional shape before they...
(Chemistry and Pharmacology of Anticancer Drugs)
Heat Shock Proteins (HSP)
These constitute a large family of immunomodulatory agents [67]. Their traditional function is to serve as protein-folding chaperones, and as hallmarks of exosomes, being found in nearly all proteomic studies of MP, especially HSP-70. Several appear to have neuron-specific functions. For example, antibodies...
(Inflammatory Disorders of the Nervous System: Pathogenesis, Immunology, and Clinical Management)
Glutamine Supplementation and Heat Shock Proteins
The induction of HSPs is a key mechanism, which provides cellular protection against systemic inflammation and renders cells more resistant to extreme stress. Because glutamine upregulates the expression of HSP-70 in animal models (Wischmeyer et al. 2001), its effect on HSP in critically ill patients...
(Glutamine : biochemistry, physiology, and clinical applications)
GLUTAMINE AND HEAT SHOCK PROTEINS
Experimental data on cell culture extensively reported that glutamine has protective effect on cells by inducing the production of heat shock proteins (HSPs), which protect cells against toxic agents or pathologic insults (Wischmeyer 2002, 2007). Indeed, glutamine enhanced HSP expression in human peripheral...
(Glutamine : biochemistry, physiology, and clinical applications)
G lutamine and Heat Shock Proteins in Immunity and Inflammation
Heat Shock Proteins Heat shock proteins (HSPs) are highly conserved proteins functioning in the unstressed state as intracellular molecular chaperones, maintaining homeostatic function, including protein refolding, movement of proteins across membranes, and gene regulation (Leppa and Sistonen,...
(Glutamine : biochemistry, physiology, and clinical applications)
Heat Shock Proteins
Heat shock proteins (HSPs) are highly conserved proteins functioning in the unstressed state as intracellular molecular chaperones, maintaining homeostatic function, including protein refolding, movement of proteins across membranes, and gene regulation (Leppa and Sistonen, 1997). Cellular stress affects...
(Glutamine : biochemistry, physiology, and clinical applications)
GLUTAMINE AND HEAT SHOCK PROTEINS IN EXERCISE
There is substantial evidence that glutamine is important for heat shock protein (HSP) generation in both in vitro and in vivo studies, for example, to help prevent atrophy of intestinal epithelial cells via HSP70 (Wischmeyer, 2002; Agostini and Biolo, 2009; Xue et al., 2011). Fehrenbach...
(Glutamine : biochemistry, physiology, and clinical applications)
Heat Shock Proteins: Role and Mechanism of Action
Suneha Goswami1, Kavita Dubey1, Khushboo Singh1, Gyanendra K. Rai2 and Ranjeet Ranjan Kumar1 division of Biochemistiy, IARI, New Delhi 2School of Biotechnology, Sher-e- Kashmir University of Agricultural Sciences and Technology’ of Jammu-180009 (J&K) E-mail: ranjeetranjaniari@gmail.com...
(Abiotic Stress Tolerance Mechanisms in Plants)
Heat Shock Proteins
During evolution, plants have developed sophisticated mechanisms to sense the subtle changes of gr owth conditions, and trigger signal transduction cascades, which in him activate stress responsive genes and ultimately lead to changes at the physiological and biochemical levels.Abiotic stress especially...
(Abiotic Stress Tolerance Mechanisms in Plants)