Category
- PI3K/Akt/mTOR
- Epigenetics
- Methylation
- Immunology & Inflammation
- Protein Tyrosine Kinase
- Angiogenesis
- Apoptosis
- Autophagy
- ER stress & UPR
- JAK/STAT
- MAPK
- Cytoskeletal Signaling
- Cell Cycle
- TGF-beta/Smad
- DNA Damage
- Stem Cells & Wnt
- Ubiquitin
- Neuronal Signaling
- NF-κB
- GPCR & G Protein
- Endocrinology & Hormones
- Transmembrane Transporters
- Metabolism
- Proteases
- Microbiology
- Others
Archives
ER stress & UPR
NVP-AUY922, a novel HSP90 inhibitor, inhibits the progression of malignant pheochromocytoma in vitro and in vivo
103 | May 31 2019
Lian J et al. showed that NVP-AUY922 exhibits potent anti-PCC activities in vitro and in vivo and represents a promising therapeutic small molecule for treating malignant PCC. [Read the Full Post]
Quantitative phosphoproteomic analysis of acquired cancer drug resistance to pazopanib and dasatinib
114 | May 26 2019
Vyse S et al. provided a useful resource detailing the candidate signalling determinants of acquired TKI resistance; and reveals a therapeutic approach of inhibiting HSP90 function as a means of salvage therapy to overcome pazopanib and dasatinib resistance. [Read the Full Post]
Drug sensitivity profiling identifies potential therapies for lymphoproliferative disorders with overactive JAK/STAT3 signaling
133 | May 06 2019
Kuusanmäki H et al. showed alternative approaches to inhibit STAT3 activity and suggest Hsp90 as a therapeutic target in lymphoproliferative disorders with constitutively active STAT3. [Read the Full Post]
Tanespimycin as antitumor therapy
229 | Feb 24 2019
Dimopoulos MA et al. showed that tanespimycin represents a promising new agent for the treatment of relapsed/refractory MM. Results of ongoing and future trials will determine the role of tanespimycin both in MM and other malignancies, including breast cancer. [Read the Full Post]
Effects of cancer-associated point mutations on the structure, function, and stability of succinate dehydrogenase A
210 | Feb 22 2019
Cao ZF et al. provided information important for understanding the molecular mechanisms of SDHA mutations in tumors. [Read the Full Post]
Down-Regulation of AQP4 Expression via p38 MAPK Signaling in Temozolomide-Induced Glioma Cells Growth Inhibition and Invasion Impairment
196 | Jan 19 2019
Chen Y et al. identified that TMZ might have therapeutic potential for controlling proliferation, invasion of malignant glioma by inhibiting AQP4 expression through activation of p38 signal transduction pathway. [Read the Full Post]
Inhibition of related JAK/STAT pathways with molecular targeted drugs shows strong synergy with ruxolitinib in chronic myeloproliferative neoplasm
316 | Jan 08 2019
Barrio S et al. showed the combination of ruxolitinib with inhibitors that target these pathways has a strong synergistic effect, which may be due to decreased activation of the common effector, STAT5. [Read the Full Post]
RCN1 suppresses ER stress-induced apoptosis via calcium homeostasis and PERK-CHOP signaling
262 | Nov 24 2018
Xu S et al. indicated that RCN1, a target of NF-κB, suppresses ER calcium release by binding to IP3R1 and decreases the UPR, thereby inhibiting ER stress-induced apoptosis. [Read the Full Post]
Synergistic cytotoxicity of BIIB021 with triptolide through suppression of PI3K/Akt/mTOR and NF-κB signal pathways in thyroid carcinoma cells
1279 | Oct 07 2018
Kim SH et al. suggested that BIIB021 has a cytotoxic activity accompanied by regulation of hsp90 client proteins in thyroid carcinoma cells. Moreover, the synergism between BIIB021 and triptolide in induction of cytotoxicity is associated with the inhibition of PI3K/Akt/mTOR and NF-κB signal pathways, the underexpression of survivin and the activation of DNA damage response in thyroid carcinoma cells. [Read the Full Post]
The non-Geldanamycin Hsp90 inhibitors enhanced the antifungal activity of fluconazole
645 | Jun 09 2018
Li L et al. showed that the activity of FLC against C. albicans biofilm formation in vitro is significantly enhanced when used in combination with HSP990. [Read the Full Post]
Calcineurin complex isolated from T-cell acute lymphoblastic leukemia (T-ALL) cells identifies new signaling pathways including mTOR/AKT/S6K whose inhibition synergize with calcineurin inhibition to promote T-ALL cell death
0 | May 31 2018
Tosello V et al. identified AKT inhibition as a novel promising drug combination to potentiate the pro-apoptotic effects of Cn inhibitors. [Read the Full Post]
Etoposide Induces Apoptosis in Activated Human Hepatic Stellate Cells via ER Stress
543 | May 31 2018
Wang C et al. demonstrated that VP-16 exerts a proapoptotic effect on LX-2 cells and has an antifibrogenic effect on collagen deposition, suggesting a new strategy for the treatment of liver fibrosis. [Read the Full Post]
Glucocorticoids Prevent Enterovirus 71 Capsid Protein VP1 Induced Calreticulin Surface Exposure by Alleviating Neuronal ER Stress
504 | May 29 2018
Hu DD et al. identified VP1-promoted Ecto-CRT upregulation as a novel mechanism of EV71-induced neuronal cell damage and highlight the potential of the use of glucocorticoids to treat severe HFMD patients with CNS complications. [Read the Full Post]
Pharmacological Inhibition of PERK Attenuates Early Brain Injury After Subarachnoid Hemorrhage in Rats Through the Activation of Akt
534 | May 19 2018
Yan F et al. found that PERK might serve as a promising target for future therapeutic intervention. [Read the Full Post]
Lipopolysaccharide and heat stress impair the estradiol biosynthesis in granulosa cells via increase of HSP70 and inhibition of smad3 phosphorylation and nuclear translocation
743 | May 01 2018
Li H et al. suggested that LPS and heat stress could impair estradiol biosynthesis in GCs via increased HSP70 and indirect inhibition of Smad3 phosphorylation and nuclear translocation. [Read the Full Post]
Connexin 32-mediated cell-cell communication is essential for hepatic differentiation from human embryonic stem cells
506 | Apr 22 2018
Qin J et al. suggested that Cx32 is essential for cell-cell interactions that facilitate driving hESCs through hepatic-lineage maturation. Regulators of both Cx32 and other members of its pathways maybe used as a promising approach on regulating hepatic lineage restriction of pluripotent stem cells and optimizing their functional maturation. [Read the Full Post]
4-Hydroxy-2-nonenal induces apoptosis by activating ERK1/2 signaling and depleting intracellular glutathione in intestinal epithelial cells
735 | Apr 08 2018
Ji Y et al. provided new insights into a functional role of MKP-1 in oxidative stress-induced cell death by regulating ERK1/2 MAP kinase in intestinal epithelial cells. [Read the Full Post]
Targeting Autophagy Sensitizes BRAF-Mutant Thyroid Cancer to Vemurafenib
497 | Apr 05 2018
Wang W et al. demonstrated that vemurafenib induces ER stress response-mediated autophagy in thyroid cancer and autophagy inhibition may be a beneficial strategy to sensitize BRAF-mutant thyroid cancer to vemurafenib. [Read the Full Post]
Late-stage inhibition of autophagy enhances calreticulin surface exposure
578 | Mar 07 2018
Li DD et al. highlight the potential of the combined use of ER stress inducers and autophagy late-stage inhibitors to reestablish and strengthen both the CRT exposure and immunogenicity of chemotherapeutic agents induced death cells. [Read the Full Post]
AKT is indispensable for coordinating Par-4/JNK cross talk in p21 downmodulation during ER stress
736 | Jan 10 2018
Rasool RU et al. found that 3-AWA inhibits colorectal tumor growth and formation of colorectal polyps at a tolerable dose, similar to the first-line drug for colorectal cancer-5-fluorouracil. [Read the Full Post]
Vascular CXCR4 Expression Promotes Vessel Sprouting and Sensitivity to Sorafenib Treatment in Hepatocellular Carcinoma
653 | Dec 22 2017
Xu J et al. revealed that CXCR4 is a novel HCC vascular marker for vessel sprouting and could serve as a potential therapeutic target and a predictive factor for sorafenib treatment in patients with HCC. [Read the Full Post]
Icaritin activates JNK-dependent mPTP necrosis pathway in colorectal cancer cells
0 | Dec 01 2017
Zhou C et al. showed that ICT exerts potent inhibitory effect against CRC cells in vitro and in vivo. JNK-dependent mPTP necrosis pathway could be key mechanism responsible for ICT's actions. [Read the Full Post]
HSP90 activity is required for MLKL oligomerisation and membrane translocation and the induction of necroptotic cell death
1060 | Nov 29 2017
Jacobsen AV et al. implicated HSP90 as a modulator of necroptosis at the level of MLKL, a function that complements HSP90's previously demonstrated modulation of the upstream necroptosis effector kinases, RIPK1 and RIPK3. [Read the Full Post]
The HSP90 inhibitor XL888 overcomes BRAF inhibitor resistance mediated through diverse mechanisms
1325 | Nov 25 2017
Paraiso KH et al.showed that HSP90 inhibition may be a highly effective strategy at managing the diverse array of resistance mechanisms being reported to BRAF inhibitors and appears to be more effective at restoring BIM expression and downregulating Mcl-1 expression than combined MEK/PI3K inhibitor therapy. [Read the Full Post]
Hsp90β promoted endothelial cell-dependent tumor angiogenesis in hepatocellular carcinoma
1104 | Nov 24 2017
Meng J et al. investigated the correlation between Hsp90β expression and CD31+ endothelial cell-dependent vessel density. [Read the Full Post]
HSP90 Shapes the Consequences of Human Genetic Variation
0 | Nov 14 2017
Karras GI et al. provided one plausible mechanism for the variable expressivity and environmental sensitivity of genetic diseases. [Read the Full Post]
Icaritin activates JNK-dependent mPTP necrosis pathway in colorectal cancer cells
810 | Nov 11 2017
Zhou C et al. showed that ICT exerts potent inhibitory effect against CRC cells in vitro and in vivo. [Read the Full Post]
Canonical hedgehog signalling regulates hepatic stellate cell-mediated angiogenesis in liver fibrosis
1258 | Oct 16 2017
Zhang F et al. provided evidence that the canonical hedgehog pathway controlled HSC-mediated liver angiogenesis. Selective inhibition of HSC hedgehog signalling could be a promising therapeutic approach for hepatic fibrosis. [Read the Full Post]
SP600125 enhances the anti-apoptotic capacity and migration of bone marrow mesenchymal stem cells treated with tumor necrosis factor-α
810 | Oct 11 2017
Wei B et al. suggested that SP600125 is of potential use in promoting the regeneration of bone and cartilage in OA and RA. [Read the Full Post]
HSP90 Shapes the Consequences of Human Genetic Variation
0 | Sep 26 2017
Karras GI et al. provided one plausible mechanism for the variable expressivity and environmental sensitivity of genetic diseases. [Read the Full Post]
HSP90 Shapes the Consequences of Human Genetic Variation
1226 | Sep 25 2017
Karras GI et al. provided one plausible mechanism for the variable expressivity and environmental sensitivity of genetic diseases. [Read the Full Post]
Hyperthermia reduces migration of osteosarcoma by suppression of autocrine motility factor
1286 | Sep 09 2017
Nakajima K et al. indicated hyperthermia reduced AMF expression and tumor cell motility via HSP27 and may therefore be applied as osteosarcoma treatment. [Read the Full Post]
TIMP-1 expression induced by IL-32 is mediated through activation of AP-1 signal pathway
0 | Aug 18 2017
Xu H, et al. believed that IL-32 might be involved in the pathogenesis of hepatic fibrosis by inducing TIMP-1 expression. [Read the Full Post]
A repurposing strategy for Hsp90 inhibitors demonstrates their potency against filarial nematodes
0 | Jun 05 2017
Gillan V et al. provided proof of principle that the repurposing of currently available Hsp90 inhibitors may have potential for the development of novel agents with macrofilaricidal properties. [Read the Full Post]
Urotensin II-induced insulin resistance is mediated by NADPH oxidase-derived reactive oxygen species in HepG2 cells
990 | Apr 22 2017
Li YY et al. found that UII induces insulin resistance, and this can be reversed by JNK inhibitor SP600125 and antioxidant/NADPH oxidase inhibitor apocynin targeting the insulin signaling pathway in HepG2 cells. [Read the Full Post]
A Repurposing Strategy for Hsp90 Inhibitors Demonstrates Their Potency against Filarial Nematodes
1 | Mar 27 2017
Gillan V et al provided proof of principle that the repurposing of currently available Hsp90 inhibitors may have potential for the development of novel agents with macrofilaricidal properties. [Read the Full Post]
Heat shock protein 90 inhibitors induce functional inhibition of human natural killer cells in a dose-dependent manner
1448 | Mar 14 2017
Huyan T et al. suggested that more attention should be given to the effect of Hsp90 inhibitors on NK cell function during clinical trials and also represent a potential immunosuppressant strategy. [Read the Full Post]
Icaritin activates JNK-dependent mPTP necrosis pathway in colorectal cancer cells
1110 | Feb 18 2017
Zhou C, et al.'s results showed that ICT exerts potent inhibitory effect against CRC cells in vitro and in vivo. JNK-dependent mPTP necrosis pathway could be key mechanism responsible for ICT's actions. [Read the Full Post]
Palmitate increases musclin gene expression through activation of PERK signaling pathway in C2C12 myotubes
0 | Feb 14 2017
Gu N, et al.'s findings suggest that palmitate increases musclin gene expression via the activation of the PERK signaling pathway in C2C12 myotubes. [Read the Full Post]
Nitric oxide plays a dual role in the oxidative injury of cultured rat microglia but not astroglia
0 | Feb 04 2017
Wang JY et al. suggested that NO exhibits a concentration-dependent dual action of weakening or enhancing oxidative injury in mixed glia, particularly microglia. [Read the Full Post]
A repurposing strategy for Hsp90 inhibitors demonstrates their potency against filarial nematodes
3345 | Jan 29 2017
Gillan V et al. provided proof of principle that the repurposing of currently available Hsp90 inhibitors may have potential for the development of novel agents with macrofilaricidal properties. [Read the Full Post]
Nitric oxide plays a dual role in the oxidative injury of cultured rat microglia but not astroglia
0 | Jan 26 2017
Wang JY et al. suggested that NO exhibits a concentration-dependent dual action of weakening or enhancing oxidative injury in mixed glia, particularly microglia. [Read the Full Post]
Heat shock protein 90 inhibitors induce functional inhibition of human natural killer cells in a dose-dependent manner
1555 | Jan 22 2017
Huyan T, et al.'s findings suggest that more attention should be given to the effect of Hsp90 inhibitors on NK cell function during clinical trials and also represent a potential immunosuppressant strategy. [Read the Full Post]
Icaritin activates JNK-dependent mPTP necrosis pathway in colorectal cancer cells
1470 | Jan 08 2017
Zhou C, et al.‘s results showed that ICT exerts potent inhibitory effect against CRC cells in vitro and in vivo. JNK-dependent mPTP necrosis pathway could be key mechanism responsible for ICT's actions. [Read the Full Post]
Palmitate increases musclin gene expression through activation of PERK signaling pathway in C2C12 myotubes
1163 | Jan 07 2017
Gu N et al. suggested that palmitate increases musclin gene expression via the activation of the PERK signaling pathway in C2C12 myotubes. [Read the Full Post]
Nitric oxide plays a dual role in the oxidative injury of cultured rat microglia but not astroglia
1885 | Jan 01 2017
Wang JY et al. suggested that NO exhibits a concentration-dependent dual action of weakening or enhancing oxidative injury in mixed glia, particularly microglia. [Read the Full Post]
TIMP-1 expression induced by IL-32 is mediated through activation of AP-1 signal pathway
1397 | Dec 07 2016
Xu H et al. believe that IL-32 might be involved in the pathogenesis of hepatic fibrosis by inducing TIMP-1 expression. [Read the Full Post]
Arsenic trioxide mediates HAPI microglia inflammatory response and subsequent neuron apoptosis through p38/JNK MAPK/STAT3 pathway
1563 | Oct 17 2016
Mao J et al. highlighted that the secretion of IL-1β and STAT3 activation induced by Arsenic trioxide can be mediated by elevation of P38/JNK MAPK in HAPI microglia cells and then induced the toxicity of neurons. [Read the Full Post]
The roles of physiological and synthetic IAP antagonism on c-IAP1/2 degradation
2796 | Mar 04 2015
Kocab et al. took a system approach to extensively compare the transcriptional programs triggered by CD30, which can degrade c-IAPs to SM-164, a synthetic IAP antagonist induces c-IAP degradation. [Read the Full Post]
SP600125 is a reversible ATP competitive inhibitor
2708 | Jan 14 2014
SP600125 is originally characterized as a selective ATP-competitive inhibitor of c-Jun N-terminal kinase JNK. [Read the Full Post]
SP600125 is supplied as a lyophilized powder
2870 | Apr 26 2013
SP600125 is originally characterized as a selective ATP-competitive inhibitor of c-Jun N-terminal kinase JNK. In Jurkat T cells, SP600125 inhibits the phosphorylation of c-Jun with IC50 of 5 μM to 10 μM. [Read the Full Post]
ONCOGENES AND HSP90 INHIBITORS
4428 | Aug 24 2012
PATHWAY OF HSP90 AND CANCER CELL LINES: Heat shock protein 90 or Hsp90 is actually a non-fibrous protein which gained its name from its molecular weight that is 90kDa. Hsp90 is most abundant cytoplasmic protein which plays a significant role in cells by acting like a molecular chaperone for many proteins related to some important signaling cascades of the cell. Different proteins chaperones that are existing in the cell, involve serine/theronine kinases and tyrosine kinases as well hence they are very much important for the proper regulation of cell growth and cell cycle. A detailed research is carried out to describe the relation between Hsp90 and cancers. To inhibit this chaperone i.e. Hsp90, the simple strategy of designing Hsp protein inhibitor was developed when Hsp90 was found to be existing in different cancerous cell lines activated through the activation of oncogenes. It has been proved a very fruitful therapy for cancer. [Read the Full Post]
HSP90 INHIBITORS AND ONCOGENES
4696 | Aug 16 2012
HSP90 CASCADE AND CANCER CELLS: Hsp90 or the Heat shock protein 90 is a non fibrous protein that gained its name on the basis of its molecular weight i.e., 90kDa. Heat shock protein 90 is the most abundant protein present in cytoplasm that plays a significant role in the cells by acting as molecular chaperones for different proteins associated with some important signaling pathways in the cells. Various molecular chaperones existing in the cells, involves in the tyrosine kinases and serine/theronine kinases as well, so they are very important for proper regulation of cell cycle and cell growth. A complete research has been done to describe the relation between cancer and Hsp90. For the inhibition of Hsp90 chaperone a simple strategy is designed i.e., development of Hsp-60 inhibitor in case of presence of Hsp90 in the cancerous cells and activated by the activation of various oncogenes. It was proved to be an efficient therapy for the treatment of cancer. [Read the Full Post]
HSP90 INHIBITORS AND ONCOGENES
4448 | Aug 02 2012
HSP90 PATHWAY AND CANCER CELLS: Heat shock protein 90 or Hsp90 is a non-fibrous protein that has gained its name from its 90kDa molecular weight. This is the most abundant protein present in cytoplasm and plays an important role in the cell by acting as a chaperone for many of the proteins involved in important signaling pathways of the cell. There are various proteins chaperones which are present in the cell, includes TKs or tyrosine kinases and theronine/serine kinases as well and these are very important for the regulation of cell cycle and growth. Detailed research has been conducted to connect cancers and Hsp90. As Hsp90 has shown by different cancerous cells which are activated via activating oncogenes a simple strategy for the inhibition of this chaperone has developed by designing Hsp90 inhibitors. This approach has been fruitful for cancer therapy. [Read the Full Post]
HSP INHIBITORS AGAINST PROTEIN FOLDING
3739 | Mar 19 2012
Introduction: Cellular Quality Assurance The network of chemical reactions linked to the mechanisms behind cellular growth, proliferation and differentiation are complex. Referred to as biochemical pathways these mechanisms operate on some simple principles starting with the receipt of a message from the host system to the cell itself. The pathway system can be likened to a production line facility with the product being a normal health cell. So mechanisms exists for stock piling of raw materials, for the synthesis of component parts, for the recycling of waste materials, for the removal of unwelcome molecules, quality assurance and final product viability. One the key aspects of cellular growth is the delicacy of the whole process, it does not take much to drive a mechanism off balance and produce a faulty product, to ensure quality under stress induced conditions a series of proteins exist referred to as Heat Shock Proteins that assess the quality of proteins being constructed for cell growth purposes. [Read the Full Post]
JNK, a potential therapeutic target for the treatment of nephrotoxicity
3306 | Nov 14 2011
Nephrotoxicity is a poisonous effect of some substances, including toxic chemicals and medication, on the kidneys, and cyclosporine (CsA) nephrotoxicity is one kind of nephrotoxicity. It is reported that the epithelial to mesenchymal transition(EMT) is an important mechanism contributing to the pathogenesis of cyclosporine (CsA) nephrotoxicity by promoting the generation of myofibroblasts. Some studies suggested that he endoplasmic reticulum (ER) stress as a potential mechanism may participate in the modulation of tubular cell plasticity in CsA-induced EPCs[1]. However, the precise mechanisms have not been known. [Read the Full Post]
Roles of Hsp90 in wound healing and cancer
4933 | Oct 24 2011
Wound healing is an intricate process in which the skin (or another organ-tissue) repairs itself after injury. At present, local growth factors are considered to be the driving force for wound healing and only recombinant human platelet-derived growth factor-BB (PDGF-BB) has been approved by US FDA for topical treatment of diabetic ulcers. However, the use of PDGF-BB in clinical trials has been limited for its modest efficacy, high cost and risk of causing cancer. Thus, novel treatment for wound healing is needed to be explored. [Read the Full Post]
Chiosis, G., M. Vilenchik, et al. (2004). "Hsp90: the vulnerable chaperone." Drug Discov Today 9(20): 881-888.
3665 | Apr 19 2011
Agents that interact with its C-terminus or modify its post-translational status represent additional ways of interfering with chaperone activity. This review will discuss several emerging classes of Hsp90 inhibitors and their modes of action. [Read the Full Post]
Davis, R. J. (2000). "Signal transduction by the JNK group of MAP kinases." Cell 103(2): 239-252.
3880 | Mar 9 2011
This is an classic review which introduce role of the JNK Signaling Pathway in MAPKKK pathway, cell survival and apoptosis. [Read the Full Post]
