ER stress & UPR

[Correlation between low expression of Hsp90 protein in keratinocytes and the number of small extracellular vesicles and its potential clinical significance]

1 | Sep 17 2022

Jun Chen et al. found that the secretion of sEVs in HaCaT cells. sEVs may be involved in the transfer of molecules between epithelial cells and immune cells. [Read the Full Post]

Delay of endothelial cell senescence protects cerebral barrier against age-related dysfunction: role of senolytics and senomorphics

2 | Sep 16 2022

Jingyuan Ya et al. found that effectively mitigate accumulation of senescent endothelial cells in cerebrovasculature might prevent age-related BBB dysfunction and might be of prophylactic or therapeutic value to extend lifelong health and wellbeing. [Read the Full Post]

Identification of potential immunotherapy biomarkers for breast cancer by bioinformatics analysis

1 | Sep 16 2022

Yao Song et al. found that CD24, MMP1, SDC1, and SPP1 were potentially associated with five immune cell types infiltration (CD8+ T cells, CD4+ T cells, neutrophils, macrophages,and dendritic cells) by TIMER. [Read the Full Post]

Autophagic sequestration of SQSTM1 disrupts the aggresome formation of ubiquitinated proteins during proteasome inhibition

1 | Sep 15 2022

Chenliang Zhang et al. demonstrated that in the early stage of proteasome inhibition, the maturation of the autophagosome was suppressed, which facilitated aggresome formation of misfolded proteins. [Read the Full Post]

Non-small cell lung cancer with EGFR exon 20 insertion mutation: a systematic literature review and meta-analysis of patient outcomes

3 | Sep 05 2022

Christina Soeun Kwon et al. found EGFR exon 20 insertion mutations as the availability of new targeted treatments might offer additional therapeutic options to these patients. [Read the Full Post]

A Low Membrane Hsp70 Expression in Tumor Cells With Impaired Lactate Metabolism Mediates Radiosensitization by NVP-AUY922

4 | Sep 05 2022

Melissa Schwab et al. found that the membrane Hsp70 density, but not cytosolic HSP levels determined the radiosensitizing effect of the Hsp90 inhibitor NVP-AUY922 in LDH-/- cells. [Read the Full Post]

Covalent JNK inhibitor, JNK-IN-8, suppresses tumor growth in triple-negative breast cancer by activating TFEB and TFE3 mediated lysosome biogenesis and autophagy

6 | Aug 28 2022

Milad Soleimani et al. demonstrated the efficacy of JNK-IN-8 as a targeted therapy for TNBC and revealed its novel lysosome- and autophagy-mediated mechanism of action. [Read the Full Post]

Hesperidin Protects Human HaCaT Keratinocytes from Particulate Matter 2.5-Induced Apoptosis via the Inhibition of Oxidative Stress and Autophagy

68 | Jul 30 2022

Pincha Devage Sameera Madushan Fernando et al. found that hesperidin showed therapeutic potential against PM2.5-induced skin damage by mitigating excessive ROS accumulation, autophagy, and apoptosis. [Read the Full Post]

The beneficial effect of salubrinal on neuroinflammation and neuronal loss in intranigral LPS-induced hemi-Parkinson disease model in rats

283 | Mar 18 2022

Fatma Nihan Cankara et al. found that salubrinal was attenuating several inflammatory mediators and thereby decreased the inflammatory effects of LPS in the neurons of the SN. [Read the Full Post]

Inhibition MNK-eIF4E-β-catenin preferentially sensitizes gastric cancer to chemotherapy

467 | Feb 25 2022

Xiaolin Yang et al. provided preclinical evidence to initialize clinical trials for gastric cancer using tomivosertib in combination with chemotherapy. [Read the Full Post]

The heat shock response, determined by QuantiGene multiplex, is impaired in HD mouse models and not caused by HSF1 reduction

332 | Feb 14 2022

Casandra Gomez-Paredes et al. found that following pharmacological activation in vivo,the heat shock response impairment in tibialis anterior, brain hemispheres and striatum was comparable between zQ175 and R6/2 mice. [Read the Full Post]

Osthole Exerts Inhibitory Effects on Hypoxic Colon Cancer Cells via EIF2[Formula: see text] Phosphorylation-mediated Apoptosis and Regulation of HIF-1[Formula: see text]

202 | Feb 13 2022

Kui-Yuan Peng et al. thought that osthole might be a potential agent in the treatment of colon cancer. [Read the Full Post]

Drug-repurposing against COVID-19 by targeting a key signaling pathway: An in silico study

342 | Feb 13 2022

Ki Kwang Oh et al. provided three key elements to alleviate COVID-19 symptoms might be anti-inflammatory effects on SARs-CoV-2-infected lung cells. [Read the Full Post]

Performance of noninvasive tests of fibrosis among Asians, Hispanic and non-Hispanic Whites in the STELLAR trials

285 | Feb 11 2022

Vincent Wai-Sun Wong et al. found that the diagnostic performance of routinely available noninvasive tests for the detection of advanced fibrosis due to NASH was acceptable and similar between White and Asian patients. [Read the Full Post]

Lumican silencing alleviates tumor necrosis factor-α-induced nucleus pulposus cell inflammation and senescence by inhibiting apoptosis signal regulating kinase 1/p38 signaling pathway via inactivating Fas ligand expression

185 | Feb 11 2022

Zhenqiang Li et al. found that interference with LUM effectively mitigated TNF-α-induced inflammatory response, cell cycle arrest, and cell senescence. [Read the Full Post]

P90 ribosomal S6 kinase confers cancer cell survival by mediating checkpoint kinase 1 degradation in response to glucose stress

292 | Feb 04 2022

Ying Ma indicates that p90 RSK promotes CHK1 phosphorylation at Ser280 and its subsequent degradation, which allows cancer cells to escape from checkpoint signals under the stress of glucose deprivation, leading to cell survival and thus contributing to tumorigenesis. [Read the Full Post]

A Novel Role for the Regulatory Nod-Like Receptor NLRP12 in Anti-Dengue Virus Response

323 | Jan 28 2022

Xingyu Li et al. demonstrated a novel mechanism that NLRP12 exerted anti-viral properties in DENV and other flaviviruses (JEV, YFV, ZIKV) infection. [Read the Full Post]

The main difference between Alvespimycin vs. 17-DMAG. Biomimetic Platform Based on Mesoporous Platinum for Multisynergistic Cancer Therapy

337 | Jan 27 2022

Gaoqian Zhao et al. showed that 17-DMAG/MPNPs@PM could accumulate in the tumor and effectively inhibit the growth of tumor cells. [Read the Full Post]

Regulation of the mammalian maternal-to-embryonic transition by eukaryotic translation initiation factor 4E

456 | Jan 18 2022

Yan Li et al. thought that eIF4E activity was regulated at key embryonic transitions in the mammalian embryo and was essential for the successful transition from maternal to embryonic control of development. [Read the Full Post]

Single cell transcriptomic profiling of neurodegeneration mediated by tau in a novel 3D neuron-astrocyte coculture model

330 | Jan 14 2022

Hannah Rickner et al. demonstrated the power to model the reduction of tau pathology by drug treatment. [Read the Full Post]

Osteoprotegerin regulates vascular function through syndecan-1 and NADPH oxidase-derived reactive oxygen species

341 | Jan 08 2022

Rhéure Alves-Lopes et al. identified novel molecular mechanisms beyond calcification for OPG, which might underlie vascular injurious effects of osteogenic factors in conditions such as hypertension and/or diabetes. [Read the Full Post]

Combination of Ocimum sanctum extract and Levetiracetam ameliorates cognitive dysfunction and hippocampal architecture in rat model of Alzheimer's disease

352 | Jan 03 2022

H S Nandini et al. provided evidence for use of OSE, LEV and OSE+LEV against AD and epilepsy associated with AD in Aβ induced AD animal model. [Read the Full Post]

Phase 1 multicenter study of the HSP90 inhibitor SNX-5422 plus carboplatin and paclitaxel in patients with lung cancers

435 | Dec 17 2021

Martin Gutierrez et al. found that the triplet combination of SNX-5422, carboplatin and paclitaxel followed by maintenance SNX-5422 therapy was well-tolerated and showed anti-tumor activity. [Read the Full Post]

Oral Hsp90 inhibitor SNX-5422 attenuates SARS-CoV-2 replication and dampens inflammation in airway cells

433 | Dec 16 2021

Ria Goswami et al. found that SNX-5422 interrupted expression of host factors demonstrated to be crucial for SARS-CoV-2 replication. [Read the Full Post]

HSP90 inhibition downregulates DNA replication and repair genes via E2F1 repression

534 | Dec 05 2021

Hanqing Liu et al. found that HSP90 inhibitors might be useful in combination therapies for MCL. [Read the Full Post]

Investigation of anticancer activities of STA-9090 (ganetespib) as a second generation HSP90 inhibitor in Saos-2 osteosarcoma cells

520 | Dec 05 2021

Aykut Özgür found the down-regulation of the expression levels of oncogenic genes. [Read the Full Post]

Co-Expression of CD34, CD90, OV-6 and Cell-Surface Vimentin Defines Cancer Stem Cells of Hepatoblastoma, Which Are Affected by Hsp90 Inhibitor 17-AAG

601 | Oct 26 2021

Mieun Lee-Theilen et al. identified CSCs of hepatoblastoma using CD34, CD90, OV-6 and csVimentin. [Read the Full Post]

ZCCHC14 regulates proliferation and invasion of non-small cell lung cancer through the MAPK-P38 signalling pathway

719 | Oct 25 2021

Xiuying Shi et al. found that ZCCHC14 could regulate proliferation and invasion of NSCLC through the P38 pathway. [Read the Full Post]

Identification of a circRNA-miRNA-mRNA regulatory network for exploring novel therapeutic options for glioma

685 | Oct 25 2021

Yi He et al. highlighted the potential pathogenesis of the circRNA-miRNA-mRNA regulatory network and identified novel therapeutic options for glioma. [Read the Full Post]

Microcystin-LR (MC-LR) Triggers Inflammatory Responses in Macrophages

722 | Oct 24 2021

Robin C Su et al. discovered that through a high-throughput, unbiased kinase activity profiling strategy, MC-LR-induced phosphorylation events were compared with potential inhibitors, and doramapimod was found to effectively prevent MC-LR-induced inflammatory responses in macrophages. [Read the Full Post]

HSP90 inhibition acts synergistically with heat to induce a pro-immunogenic form of cell death in colon cancer cells

838 | Oct 14 2021

Petros X E Mouratidis et al. found that sub-ablative heating could act synergistically with the clinically relevant HSP90 inhibitor NVP-AUY922 to induce a pro-immunogenic form of cell death in colon cancer cells. [Read the Full Post]

Evolution of kinase polypharmacology across HSP90 drug discovery

818 | Oct 13 2021

Albert A Antolin et al. found that the resorcinol clinical candidates ganetespib and, to a lesser extent, luminespib, displayed unique off-target kinase pharmacology as compared with other HSP90 inhibitors. [Read the Full Post]

Regulation and function of AP-1 in insulinoma cells and pancreatic β-cells

695 | Oct 05 2021

Tobias M Backes et al. found that AP-1 controls an important function of pancreatic β-cells in vivo, the regulation of glucose homeostasis. [Read the Full Post]

Effect of Dickkopf-1 (Dkk-1) and SP600125, a JNK Inhibitor, on Wnt Signaling in Canine Prostate Cancer Growth and Bone Metastases Wachiraphan Supsavhad 1 2, Bardes B Hassan 1 3,

1271 | Sep 05 2021

Wachiraphan Supsavhad et al. showed that SP600125 had the potential to serve as an alternative adjuvant therapy in some early-stage PCa patients, especially those with high Dkk-1 expression. [Read the Full Post]

Protective effects of NAC and salubrinal on apoptosis of retinal pigment epithelial cells induced by all-trans retinoic acid

911 | Apr 02 2021

Juan Wu et al. thought that ATRA might play an important role in the prevention, diagnosis and treatment of age-related macular degeneration. [Read the Full Post]

Mnk inhibitors: a patent review

1122 | Mar 07 2021

Ahmed M Abdelaziz et al. provided a succinct review of the current state of development of pyridone-aminal-derived Mnk inhibitors through the analysis of relevant patent applications filed in the last 5 years. [Read the Full Post]

Discovery of repurposing drug candidates for the treatment of diseases caused by pathogenic free-living amoebae

660 | Feb 25 2021

Christopher A Rice et al. demonstrated the utility of phenotypic screens for discovery of new drugs for pathogenic free-living amoebae, including Acanthamoeba for the first time. [Read the Full Post]

Correction of eIF2-dependent defects in brain protein synthesis, synaptic plasticity, and memory in mouse models of Alzheimer's disease

455 | Feb 24 2021

Mauricio M Oliveira et al. found that attenuating the ISR downstream of phosphorylated eIF2α might restore hippocampal protein synthesis and delay cognitive decline in AD patients. [Read the Full Post]

Priming with HDAC Inhibitors Sensitizes Ovarian Cancer Cells to Treatment with Cisplatin and HSP90 Inhibitors

625 | Feb 24 2021

Ana J Rodrigues Moita et al. found that priming with HDACi sensitized ovarian cancer cells to treatment with HSP90i or cisplatin and had an influence on the development of cisplatin resistance, both of which might contribute to an improved ovarian cancer treatment. [Read the Full Post]

Structure-based discovery of 1H-indole-2-carboxamide derivatives as potent ASK1 inhibitors for potential treatment of ulcerative colitis

459 | Feb 23 2021

Shaohua Hou et al. suggested that ASK1 inhibitors could potentially be used as a therapeutic strategy for UC. [Read the Full Post]

Selonsertib, a potential drug for liver failure therapy by rescuing the mitochondrial dysfunction of macrophage via ASK1-JNK-DRP1 pathway

460 | Feb 22 2021

Guohua Lou et al. thought that selonsertib protected against LPS/GalN-induced ALF by attenuating JNK-mediated DRP1 mitochondrial translocation and then rescuing mitochondrial damage in macrophages and might have therapeutic potential for early ALF patients. [Read the Full Post]

Aloe-emodin relieves zidovudine-induced injury in neonatal rat ventricular myocytes by regulating the p90rsk/p-bad/bcl-2 signaling pathway

667 | Feb 11 2021

Wei Zhao et al. indicated that AE attenuated AZT-induced cardiomyocyte apoptosis by activating p90rsk. [Read the Full Post]

Upregulation of peroxisome proliferator-activated receptor-α and the lipid metabolism pathway promotes carcinogenesis of ampullary cancer

477 | Feb 03 2021

Chih-Yang Wang et al. found that upregulation of PPARA and lipid metabolism-related genes were potential pathways in the carcinogenesis and development of ampullary cancer. [Read the Full Post]

17-DMAG dually inhibits Hsp90 and histone lysine demethylases in alveolar rhabdomyosarcoma

580 | Feb 03 2021

Shivendra Singh et al. indicated that targeting KDM in combination with chemotherapy might serve as a therapeutic approach to PAX3-FOXO1-positive aRMS. [Read the Full Post]

De novo protein synthesis is necessary for priming in preclinical models of migraine

813 | Jan 26 2021

Jacob Lackovic et al. suggested that targeting the regulation of protein synthesis might be a novel approach for new migraine treatment strategies. [Read the Full Post]

Salvianolate ameliorates oxidative stress and podocyte injury through modulation of NOX4 activity in db/db mice

609 | Jan 17 2021

Yiran Liang et al. identified that Salvianolate could prevent glucose-induced oxidative podocyte injury through modulation of NOX4 activity in DN and had a novel therapeutic potential for DN. [Read the Full Post]

Pergularia daemia alters epileptogenesis and attenuates cognitive impairment in kainate-treated mice: Insight into anti-inflammatory mechanisms

614 | Jan 12 2021

Antoine Kavaye Kandeda et al. suggested that anti-inflammatory mechanisms were involved in the antiepileptogenic effect of P. daemia extract. [Read the Full Post]

Deciphering the Inhibition Mechanism of under Trial Hsp90 Inhibitors and Their Analogues: A Comparative Molecular Dynamics Simulation

482 | Dec 28 2020

Asma Nazar et al. suggested that under trial Hsp90 inhibitors MPC-3100 could be a potential starting point into the development of potential anticancer agents with the possibility of future directions for the improvement of early existing Hsp90 inhibitors CNF-2024 and SNX-5422 as an anticancer agent. [Read the Full Post]

Heat Shock Protein 90 Inhibitors AUY922, BIIB021 and SNX5422 Induce Bim-mediated Death of Thyroid Carcinoma Cells

556 | Dec 27 2020

Si Hyoung Kim et al. found that AUY922, BIIB021 and SNX5422 induced cytotoxicity by modulating Bim and ERK1/2, AKT and AMPK signaling in thyroid carcinoma cells. [Read the Full Post]

HSP90 Inhibitor Ganetespib (STA-9090) Inhibits Tumor Growth in c-Myc-Dependent Esophageal Squamous Cell Carcinoma

572 | Dec 17 2020

Liuliu Guan et al. supported that the HSP90 inhibitor, STA-9090, suppressed the expression of the MYC protein and interferes with HSP90-MYC protein-protein interaction. [Read the Full Post]

Ganetespib in Combination with Pemetrexed-Platinum Chemotherapy in Patients with Pleural Mesothelioma (MESO-02): A Phase Ib Trial

669 | Dec 16 2020

Dean A Fennell et al. found that ganetespib could be combined safely with pemetrexed and platinum chemotherapy to treat patients with MPM. [Read the Full Post]

VDAC upregulation and αTAT1‑mediated α‑tubulin acetylation contribute to tanespimycin‑induced apoptosis in Calu‑1 cells

1951 | Nov 02 2020

Qilin Wang et al. provided evidence for the use of a combination of drugs that target VDAC1 and tubulin to induce tumour cell apoptosis. [Read the Full Post]

Identification of Subtype-Specific Metastasis-Related Genetic Signatures in Sarcoma

640 | Nov 02 2020

Ya-Ling Li et al. provided new insights into the pathogenesis, diagnosis, treatment, and prognosis of sarcomas and provided new directions for further study of sarcoma. [Read the Full Post]

Selective targeting of the αC and DFG-out pocket in p38 MAPK

445 | Nov 01 2020

Sandra Röhm et al. provided valuable insights into back-pocket interactions that were not addressed in SR-318 and it provided an alternative chemical tool with good cellular activity targeting also the p38 back pocket. [Read the Full Post]

Targeting of BCR-ABL1 and IRE1α induces synthetic lethality in Philadelphia-positive acute lymphoblastic leukemia

0 | Nov 01 2020

Margherita Vieri et al. found that the identified combined action of nilotinib and MKC-8866 might represent a successful therapeutic strategy in high-risk Ph + ALL. [Read the Full Post]

Hsp90 Inhibitor; NVP-AUY922 in Combination with Doxorubicin Induces Apoptosis and Downregulates VEGF in MCF-7 Breast Cancer Cell Line

619 | Oct 16 2020

Mahshid Mohammadian et al. indicated an effective action of NVP-AUY922 in combined with DOX in this cell line. [Read the Full Post]

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

663 | Oct 15 2020

Ankit K Rochani et al.suggested that DNP-based aqueous nanoformulations could be used in both pancreatic (MIA PaCa-2) and breast (MCF-7) cancer therapy. [Read the Full Post]

Targeting of BCR-ABL1 and IRE1α induces synthetic lethality in Philadelphia-positive acute lymphoblastic leukemia

487 | Oct 02 2020

Margherita Vieri et al. found that the identified combined action of nilotinib and MKC-8866 might represent a successful therapeutic strategy in high-risk Ph + ALL. [Read the Full Post]

GSK3β-Ikaros-ANXA4 signaling inhibits high-glucose-induced fibroblast migration

1108 | Aug 19 2020

Youpei Wang et al. provided a new regulatory mechanism by which GSK3β negatively regulated human skin fibroblast cell migration. [Read the Full Post]

A Phase I Study of PF-04929113 (SNX-5422), an Orally Bioavailable Heat Shock Protein 90 Inhibitor, in Patients With Refractory Solid Tumor Malignancies and Lymphomas

522 | Apr 19 2020

Arun Rajan et al. showed that PF-04929113 administered orally twice a week is well tolerated and inhibits its intended target Hsp90. No objective responses were seen, but long-lasting stabilizations were obtained. Although no clinically significant drug-related ocular toxicity was seen in this study, the development of PF-04929113 has been discontinued because of ocular toxicity seen in animal models and in a separate phase I study. [Read the Full Post]

SNX-2112, a Selective Hsp90 Inhibitor, Potently Inhibits Tumor Cell Growth, Angiogenesis, and Osteoclastogenesis in Multiple Myeloma and Other Hematologic Tumors by Abrogating Signaling via Akt and ERK

480 | Apr 19 2020

Yutaka Okawa et al. provided the framework for clinical studies of SNX-2112 to improve patient outcome in MM and other hematologic malignancies. [Read the Full Post]

Ganetespib limits ciliation and cystogenesis in autosomal-dominant polycystic kidney disease (ADPKD)

630 | Mar 15 2020

Nikonova AS et al. identified a new biologic activity for HSP90 and support a cilia-based mechanism for cyst repression.-Nikonova, A. S., Deneka, A. Y., Kiseleva, A. A., Korobeynikov, V., Gaponova, A., Serebriiskii, I. G., Kopp, M. C., Hensley, H. H., Seeger-Nukpezah, T. N., Somlo, S., Proia, D. A., Golemis, E. A. Ganetespib limits ciliation and cystogenesis in autosomal-dominant polycystic kidney disease (ADPKD). [Read the Full Post]

The novel HSP90 inhibitor STA-9090 exhibits activity against Kit-dependent and -independent malignant mast cell tumors

590 | Mar 15 2020

Lin TY et al. showed that STA-9090 exhibits broad activity against mast cells expressing WT or mutant Kit, suggesting it may be an effective agent in the clinical setting against mast cell malignancies. [Read the Full Post]

17-AAG inhibits vemurafenib-associated MAP kinase activation and is synergistic with cellular immunotherapy in a murine melanoma model

641 | Jan 08 2020

Joshi SS et al. indicated their sdudies support a role for 17-AAG and HSP90 inhibition in enhancing cellular immunotherapy for melanoma. [Read the Full Post]

Tanespimycin as antitumor therapy

0 | Jan 07 2020

Dimopoulos MA et al. indiacated 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]

Characteristics of Patients With ROS1+ Cancers: Results From the First Patient-Designed, Global, Pan-Cancer ROS1 Data Repository

893 | Dec 30 2019

This study is the first global, patient-designed approach, to our knowledge, to comprehensively assess demographic, clinical, and environmental characteristics associated with ROS1+ cancers. [Read the Full Post]

Highly accurate DNA-based detection and treatment results of MET exon 14 skipping mutations in lung cancer

830 | Dec 27 2019

Pruis MA et al. showed that METex14del can be reliably detected by routine DNA NGS analysis. [Read the Full Post]

Hsp90 inhibitors induce the unfolded protein response in bovine and mice lung cells

631 | Dec 19 2019

Kubra KT et al. demonstrated that Hsp90 inhibition triggers the activities of the unfolded protein response, and suggests that this molecular machinery contributes in the protective action of Hsp90 inhibitors in the lung microvasculature. [Read the Full Post]

NVP-AUY922, a novel HSP90 inhibitor, inhibits the progression of malignant pheochromocytoma in vitro and in vivo

0 | Dec 19 2019

Lian J et al. indicated 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]

Activity of the Hsp90 inhibitor luminespib among non-small-cell lung cancers harboring EGFR exon 20 insertions

627 | Dec 18 2019

Piotrowska Z et al.showed that this study met its primary end point, suggesting that luminespib may be an active therapy for advanced NSCLC patients with EGFR ins20. Luminespib is generally well-tolerated, though reversible low-grade ocular toxicity is common. Further study of luminespib and other hsp90 inhibitors in this population is warranted. [Read the Full Post]

JNK-IN-8, a c-Jun N-terminal kinase inhibitor, improves functional recovery through suppressing neuroinflammation in ischemic stroke

524 | Dec 08 2019

Zheng J et al. demonstrated that JNK-IN-8 inhibits neuroinflammation and improved neurological function by inhibiting JNK/NF-κB and is a promising agent for the prevention of ischemic brain injury. [Read the Full Post]

SP600125 suppresses Keap1 expression and results in NRF2-mediated prevention of diabetic nephropathy

587 | Oct 30 2019

Zhang H et al. demonstrated that NRF2 is required for SP600125's protection against DN. SP600125 activates NRF2 possibly via inhibition of JNK-induced Keap1 expression. [Read the Full Post]

PF-06463922 is a potent and selective next-generation ROS1/ALK inhibitor capable of blocking crizotinib-resistant ROS1 mutations

949 | Aug 05 2019

Zou HY et al. indicated that PF-06463922 has potential for treating ROS1 fusion-positive cancers, including those requiring agents with CNS-penetrating properties, as well as for overcoming crizotinib resistance driven by ROS1 mutation. [Read the Full Post]

NVP-AUY922, a novel HSP90 inhibitor, inhibits the progression of malignant pheochromocytoma in vitro and in vivo

843 | 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

775 | 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

865 | 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

1044 | 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

975 | Feb 22 2019

Cao ZF et al. provided information important for understanding the molecular mechanisms of SDHA mutations in tumors. [Read the Full Post]

Loss of ARID1A expression leads to sensitivity to ROS-inducing agent elesclomol in gynecologic cancer cells

0 | Feb 16 2019

Kwan SY et al. demonstrated for the first time that loss of ARID1A leads to accumulation of ROS and suggest that elesclomol may be used to target ARID1A-mutant gynecologic cancer cells. [Read the Full Post]

Down-Regulation of AQP4 Expression via p38 MAPK Signaling in Temozolomide-Induced Glioma Cells Growth Inhibition and Invasion Impairment

746 | 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

930 | 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

1033 | 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

3252 | 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]

Dihydromyricetin promotes autophagy and apoptosis through ROS-STAT3 signaling in head and neck squamous cell carcinoma

1577 | Sep 13 2018

Fan TF et al. found that inhibiting autophagy could enhance DHM-induced apoptosis in head and neck squamous cell carcinoma. [Read the Full Post]

Hypoxia potentiates the cytotoxic effect of piperlongumine in pheochromocytoma models

1317 | Jul 12 2018

Bullova P et al. reported for the first time that PL mediates PHEO cell death by activating both apoptosis and necroptosis in vitro and in vivo. This effect is magnified in hypoxic conditions, making PL a promising potential candidate for use as a therapeutic option for patients with PHEO/PGL, including those with SDHB mutations. [Read the Full Post]

Loss of ARID1A expression leads to sensitivity to ROS-inducing agent elesclomol in gynecologic cancer cells

1380 | Jun 20 2018

Kwan SY et al. demonstrated for the first time that loss of ARID1A leads to accumulation of ROS and suggest that elesclomol may be used to target ARID1A-mutant gynecologic cancer cells. [Read the Full Post]

The non-Geldanamycin Hsp90 inhibitors enhanced the antifungal activity of fluconazole

1339 | 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

1343 | 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

1331 | 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

1265 | 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

1390 | 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

1034 | 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

1531 | 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

1212 | 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

1286 | 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

1360 | 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

1177 | 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

1753 | 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

1970 | 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

1740 | 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

1439 | 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

2367 | 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

1293 | 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

1930 | 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

1984 | 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]

Nitric oxide generation by the organic nitrate NDBP attenuates oxidative stress and angiotensin II-mediated hypertension

0 | May 29 2017

Porpino SK et al. suggested that NDBP treatment is associated with sustained NO release and attenuated activity of NADPH oxidase, which to some extent requires functional xanthine oxidase. [Read the Full Post]

Urotensin II-induced insulin resistance is mediated by NADPH oxidase-derived reactive oxygen species in HepG2 cells

1497 | 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

2069 | 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

1616 | 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

4653 | 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

2188 | 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

1964 | 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

1735 | 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

2495 | 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

1912 | 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

2070 | 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

3376 | 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

3182 | 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

3351 | 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

5086 | 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

5398 | 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

5172 | 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

4402 | 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

3720 | 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

5663 | 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.

4321 | 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.

4387 | 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]