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Metabolism

Effect of A-769662, a direct AMPK activator, on Tlr-4 expression and activity in mice heart tissue

10 | Dec 09 2019

Rameshrad M et al. demonstrated that activation of AMPK, by A-769662 agent, could inhibit Tlr-4 expression and activity, suggesting a link between AMPK and Tlr-4 in heart tissue. [Read the Full Post]

Tipifarnib prevents development of hypoxia-induced pulmonary hypertension

0 | Dec 02 2019

Duluc L et al. demonstrated the importance of protein farnesylation in pulmonary vascular remodelling and provides a rationale for selective targeting of this pathway in pulmonary hypertension. [Read the Full Post]

First-in-Human Phase I Study of the Oral Inhibitor of Indoleamine 2,3-Dioxygenase-1 Epacadostat (INCB024360) in Patients with Advanced Solid Malignancies

20 | Nov 25 2019

Beatty GL et al. showed that epacadostat was generally well tolerated, effectively normalized kynurenine levels, and produced maximal inhibition of IDO1 activity at doses of ≥100 mg BID. Studies investigating epacadostat in combination with other immunomodulatory drugs are ongoing. [Read the Full Post]

Updates in the Clinical Development of Epacadostat and Other Indoleamine 2,3-Dioxygenase 1 Inhibitors (IDO1) for Human Cancers

22 | Nov 24 2019

Komiya T et al. indicated that IDO1 is a promising target that can improve the treatment outcome in the field of Immuno-oncology. Several orally available IDO1 inhibitors including Epacadostat have entered human clinical trials over the last few years without a major safety concern. Although there is no objective response in single-agent trials, combination regimens with PD-1 inhibitors appear to exceed the activity of PD-1 inhibitors alone. Recent phase III ECHO 301 trial testing the combination of Epacadostat with Pembrolizumab in melanoma did not show superior outcome compared to Pembrolizumab alone. This lead to halting of other phase III trials using IDO1 inhibitors. In this minireview, we will discuss the recent clinical development of Epacadostat and other IDO1 inhibitors. [Read the Full Post]

CX-4945: the protein kinase CK2 inhibitor and anti-cancer drug shows anti-fungal activity

31 | Nov 07 2019

Masłyk M et al. indicated their data unveil the dual-activity of CX-4945; when used in anti-cancer therapy, it may simultaneously prevent cancer-associated candidiasis. [Read the Full Post]

FoxO1 regulates myocardial glucose oxidation rates via transcriptional control of pyruvate dehydrogenase kinase 4 expression

20 | Nov 02 2019

Gopal K et al. demonstrated that pyruvate dehydrogenase kinase 4 is a direct transcriptional target of FoxO1 (but not FoxO3/FoxO4) in the heart. Furthermore, we report here, for the first time, that FoxO1 inhibition increases glucose oxidation in the isolated working mouse heart. [Read the Full Post]

LncRNA FER1L4 induces apoptosis and suppresses EMT and the activation of PI3K/AKT pathway in osteosarcoma cells via inhibiting miR-18a-5p to promote SOCS5

31 | Oct 03 2019

Ye F et al. indicated thatthe overexpression of FER1L4 promoted apoptosis and inhibited the EMT markers expression and PI3K/AKT signaling pathway activation in OS cells via downregulating miR-18a-5p to promote SOCS5. [Read the Full Post]

On the Mechanism of Cytoprotection by Ferrostatin-1 and Liproxstatin-1 and the Role of Lipid Peroxidation in Ferroptotic Cell Death

0 | Oct 02 2019

Zilka O et al. demonstrated that potent RTAs subvert ferroptosis and suggest that lipid peroxidation (autoxidation) may play a central role in the process. [Read the Full Post]

Optimizing lonafarnib treatment for the management of chronic delta hepatitis: The LOWR HDV-1 study

54 | Sep 05 2019

Yurdaydin C et al. showed the cytochrome P450 3A4 inhibitor, RTV, allows a lower LNF dose to be used while achieving higher levels of postabsorption LNF, yielding better antiviral responses and tolerability. In addition, combining LNF with PEG-IFNα achieved more substantial and rapid HDV-RNA reduction, compared to historical responses with PEG-IFNα alone. Twelve weeks of LNF can result in posttreatment HDV-RNA negativity in some patients, which we speculate results from restoring favorable immune responses. These results support further development of LNF with RTV boosting and exploration of the combination of LNF with PEG-IFN. [Read the Full Post]

Heme oxygenase-1 accelerates erastin-induced ferroptotic cell death

53 | Aug 06 2019

Kwon MY et al. showed that hemin and CORM accelerate the HO-1 expression in the presence of Erastin and increase membranous lipid peroxidation. Thus, HO-1 is an essential enzyme for iron-dependent lipid peroxidation during ferroptotic cell death. [Read the Full Post]

RSL3 and Erastin differentially regulate redox signaling to promote Smac mimetic-induced cell death

0 | Aug 06 2019

Dächert J et al. showed that RSL3/BV6 and Erastin/BV6 differentially regulate redox signaling and cell death in ALL cells. While RSL3/BV6 cotreatment induces ferroptotic cell death, Erastin/BV6 stimulates oxidative cell death independently of iron. These findings have important implications for the therapeutic targeting of redox signaling to enhance Smac mimetic-induced cell death in ALL. [Read the Full Post]

Irisin Is Controlled by Farnesoid X Receptor and Regulates Cholesterol Homeostasis

77 | Jun 17 2019

Li H et al. showed taht activation of FXR induces FNDC5 mRNA expression in human and increased the circulating level of Irisin in Rhesus macaques. FNDC5/Irisin is a direct transcriptional target of FXR. Irisin may be a novel therapeutic strategy for dyslipidemia and atherosclerosis. [Read the Full Post]

Lonafarnib synergizes with azoles against Aspergillus spp. and Exophiala spp

71 | Jun 13 2019

Qiao J et al. demonstrated that lonafarnib could enhance the in vitro antifungal activity of itraconazole, posaconazole and voriconazole against Aspergillus spp. and E. dermatitidis, suggesting that azoles, especially itraconazole and posaconazole, combined with farnesyltransferase inhibitor might provide a potential strategy to the management of Aspergillus and Exophiala infections. However, further studies are warranted to elucidate the underlying mechanism and to investigate the potential of reliable and safe application in clinical practice. [Read the Full Post]

CX-4945, a Selective Inhibitor of Casein Kinase 2, Synergizes with B Cell Receptor Signaling Inhibitors in Inducing Diffuse Large B Cell Lymphoma Cell Death

152 | Jun 08 2019

Mandato E et al. suggested a role for CK2 downstream of the BCR in controlling survival pathways crucial for cell growth of different DLBCL subtypes. Also, the use of CX-4945 in combination with BCR signaling blockers could represent a novel rational therapeutic approach in the DLBCL. [Read the Full Post]

Targeting FoxO1 with AS1842856 suppresses adipogenesis

83 | Jun 02 2019

Zou P et al. suggested AS1842856 can be an anti-obesity agent that warrants further investigation. [Read the Full Post]

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

168 | 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

177 | 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]

Hemin-induced platelet activation and ferroptosis is mediated through ROS-driven proteasomal activity and inflammasome activation: Protection by Melatonin

89 | May 26 2019

NaveenKumar SK et al. demonstrated an association of platelet activation/ferroptosis with proteasome activity and inflammasome activation. Although, high-throughput screening has recognized ferrostatin-1 (Fer-1) and liproxstatin-1 (Lip-1) as potent ferroptosis inhibitors, having an endogenous antioxidant such as MLT as ferroptosis inhibitor is of high interest. MLT is a well-known chronobiotic hormone that regulates the circadian rhythms in vertebrates. It is also known to exhibit potent antioxidant and ROS quenching capabilities. MLT can regulate fundamental cellular functions by exhibiting cytoprotective, oncostatic, antiaging, anti-venom, and immunomodulatory activities. The ROS scavenging capacity of MLT is key for its cytoprotective and anti-apoptotic properties. Considering the anti-ferroptotic and anti-apoptotic potentials MLT, it could be a promising clinical application to treat hemolytic, thrombotic and thrombocytopenic conditions. Therefore, we propose MLT as a pharmacological and therapeutic agent to inhibit ferroptosis and platelet activation. [Read the Full Post]

AMP-activated protein kinase (AMPK) activator A-769662 increases intracellular calcium and ATP release from astrocytes in an AMPK-independent manner

169 | May 23 2019

Vlachaki Walker JM et al. indicated that AMPK is required to maintain basal eATP levels but is not required for A-769662-induced increases in eATP. A-769662 (>50 μM) enhanced intracellular calcium levels leading to ATP release in an AMPK and purinergic receptor independent pathway. [Read the Full Post]

Tipifarnib prevents development of hypoxia-induced pulmonary hypertension

85 | May 22 2019

Duluc L et al. demonstrated the importance of protein farnesylation in pulmonary vascular remodelling and provides a rationale for selective targeting of this pathway in pulmonary hypertension. [Read the Full Post]

Effects of EF-24, RAD001, and paclitaxel on the expression profiles of apoptotic and anti-apoptotic genes

158 | May 15 2019

Alp E et al. showed that response of these cells to paclitaxel, EF-24, and RAD001 was found different at the transcriptional level of apoptotic and antiapoptotic genes. [Read the Full Post]

Effects of Epacadostat on Brain Extracellular Fluid Concentrations of Serotonin -- An Intracerebral Microdialysis Study in Sprague-Dawley Rats

138 | May 14 2019

Zhang Y et al. suggested that serotonin syndrome is unlikely following treatment with either epacadostat alone or with combination with MAOIs such as linezolid. [Read the Full Post]

Drug sensitivity profiling identifies potential therapies for lymphoproliferative disorders with overactive JAK/STAT3 signaling

228 | 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]

MPP+ induces necrostatin-1- and ferrostatin-1-sensitive necrotic death of neuronal SH-SY5Y cells

0 | May 06 2019

Ito K et al. found that MPP+ predominantly induced non-apoptotic death of neuronally differentiated SH-SY5Y cells. This cell death was strongly inhibited by necrostatin-1 (Nec-1), a necroptosis inhibitor, and by an indole-containing compound (3,3'-diindolylmethane: DIM). However, it occurred independently of receptor-interacting serine/threonine-protein kinase 1/3 (RIP1/RIP3), indicating that this form of cell death was not necroptosis. MPP+-induced cell death was also inhibited by several inhibitors of ferroptosis, including ferrostatin-1 (Fer-1). Although MPP+-induced death and ferroptosis shared some features, such as occurrence of lipid peroxidation and inhibition by Fer-1, MPP+-induced death seemed to be distinct from ferroptosis because MPP+-induced death (but not ferroptosis) was inhibited by Nec-1, was independent of p53, and was accompanied by ATP depletion and mitochondrial swelling. Further investigation of MPP+-induced non-apoptotic cell death may be useful for understanding the mechanisms of neuronal loss and for treatment of neurodegenerative diseases such as Parkinson's disease. [Read the Full Post]

Superior anti-tumor activity of the MDM2 antagonist idasanutlin and the Bcl-2 inhibitor venetoclax in p53 wild-type acute myeloid leukemia models

0 | May 04 2019

Lehmann C et al. provided functional and molecular insight on the superior anti-tumor activity of combined idasanutlin and venetoclax treatment in AML and support its further exploration in clinical studies. [Read the Full Post]

On the Mechanism of Cytoprotection by Ferrostatin-1 and Liproxstatin-1 and the Role of Lipid Peroxidation in Ferroptotic Cell Death

110 | Apr 30 2019

Zilka O et al. demonstrated that potent RTAs subvert ferroptosis and suggest that lipid peroxidation (autoxidation) may play a central role in the process. [Read the Full Post]

Nicotinamide phosphoribosyltransferase inhibitor APO866 induces C6 glioblastoma cell death via autophagy

128 | Apr 23 2019

Yang P et al indicated that APO866 induced pro-death autophagy in C6 glioblastoma cells by decreasing intracellular NAD, and low concentration of APO866 can be used as an autophagy inducer in autophagic-death sensitive glioblastoma. [Read the Full Post]

FK866-induced NAMPT inhibition activates AMPK and downregulates mTOR signaling in hepatocarcinoma cells

106 | Apr 22 2019

Schuster S et al. revealed an important role of the NAMPT-mediated NAD salvage pathway in the energy homeostasis of hepatocarcinoma cells and suggest NAMPT inhibition as a potential treatment option for HCC. [Read the Full Post]

Pre-B cell colony enhancing factor induces Nampt-dependent translocation of the insulin receptor out of lipid microdomains in A549 lung epithelial cells

117 | Apr 15 2019

Peng Q et al. concluded that PBEF can inhibit insulin signaling through the IR by Nampt-dependent promotion of IR translocation into the nonraft domains of A549 epithelial cells. PBEF-induced alterations in the spatial geometry of the IR provide a mechanistic explanation for insulin resistance in inflammatory states associated with upregulation of PBEF. [Read the Full Post]

CK2 inhibition with silmitasertib promotes methuosis-like cell death associated to catastrophic massive vacuolization of colorectal cancer cells

182 | Apr 13 2019

Silva-Pavez E et al. suggested that an aberrantly elevated expression/activity of CK2 may play a key role in CRC, promoting cell viability and proliferation in untreated cells, however, its inhibition with silmitasertib promotes methuosis-like cell death associated to massive catastrophic vacuolization, accounting for decreased tumorigenicity at later times. These characteristics of silmitasertib support a potential therapeutic use in CRC patients and probably other CK2-dependent cancers. [Read the Full Post]

Lipoxygenase-mediated generation of lipid peroxides enhances ferroptosis induced by erastin and RSL3

126 | Apr 08 2019

Shintoku R et al suggested that tumor ferroptosis is promoted by LOX-catalyzed lipid hydroperoxide generation in cellular membranes. [Read the Full Post]

Clinical evaluation of laboratory methods to monitor exposure of rivaroxaban at trough and peak in patients with atrial fibrillation

120 | Mar 15 2019

Al-Aieshy F et al. found that the POC assay for PT-INR could be useful to indicate high exposure to rivaroxaban in emergency situations although further validation is required. [Read the Full Post]

RSL3 and Erastin differentially regulate redox signaling to promote Smac mimetic-induced cell death

133 | Feb 25 2019

Dächert J et al. indicated that RSL3/BV6 and Erastin/BV6 differentially regulate redox signaling and cell death in ALL cells. While RSL3/BV6 cotreatment induces ferroptotic cell death, Erastin/BV6 stimulates oxidative cell death independently of iron. These findings have important implications for the therapeutic targeting of redox signaling to enhance Smac mimetic-induced cell death in ALL. [Read the Full Post]

Tanespimycin as antitumor therapy

310 | 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

285 | Feb 22 2019

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

The Phosphodiesterase 10A Inhibitor PF-2545920 Enhances Hippocampal Excitability and Seizure Activity Involving the Upregulation of GluA1 and NR2A in Post-synaptic Densities

142 | Feb 15 2019

Zhang Y et al. suggested it would be detrimental to use the drug in seizure patients and might cause neuronal hyperexcitability in non-epileptic individuals. [Read the Full Post]

Upregulation of hydroxysteroid sulfotransferase 2B1b promotes hepatic oval cell proliferation by modulating oxysterol-induced LXR activation in a mouse model of liver injury

0 | Feb 12 2019

Wang Z et al. indicated that upregulation of SULT2B1b might promote HOC proliferation and aggravate liver injury via the suppression of oxysterol-induced LXR activation in chemically induced mouse liver injury. [Read the Full Post]

In vivo activation of invariant natural killer T cells induces systemic and local alterations in T-cell subsets prior to preterm birth

146 | Feb 11 2019

Gomez-Lopez N et al. found that iNKT-cell activation altered the systemic and local T-cell subsets prior to preterm labour/birth; however, treatment with rosiglitazone partially reversed such effects. [Read the Full Post]

Targeting the epigenome: Screening bioactive compounds that regulate histone deacetylase activity

0 | Jan 30 2019

Godoy LD et al. provided the first step in identifying multiple bioactive compound HDAC inhibitors. [Read the Full Post]

Sildenafil suppresses the proliferation and enhances the apoptosis of hemangioma endothelial cells

137 | Jan 13 2019

He X et al. indicated the present study concluded that PDE-5 may be a potential therapeutic target for hemangiomas and Id-1 may serve a vital role in the associated signaling transduction pathways. [Read the Full Post]

Inhibition of related JAK/STAT pathways with molecular targeted drugs shows strong synergy with ruxolitinib in chronic myeloproliferative neoplasm

390 | 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]

Low-Dose Farnesyltransferase Inhibitor Suppresses HIF-1α and Snail Expression in Triple-Negative Breast Cancer MDA-MB-231 Cells In Vitro

161 | Jan 05 2019

Tanaka T et al. suggested that FTIs may be capable of ameliorating the aggressive phenotype of TNBC by suppressing the HIF-1α-Snail pathway. [Read the Full Post]

Inhibition of the Pentose-phosphate Pathway Selectively Sensitizes Leukemia Lymphocytes to Chemotherapeutics by ROS-independent Mechanism

0 | Jan 05 2019

Zhelev Z et al. suggested that 6-ANA could be used as a supplementary component in anticancer chemotherapy, and would allows therapeutic doses of anticancer drugs to be reduced, thereby minimizing their side-effects. [Read the Full Post]

Synergistic Cytotoxicity of Melatonin and New-generation Anticancer Drugs Against Leukemia Lymphocytes But Not Normal Lymphocytes

0 | Jan 04 2019

Zhelev Z et al. suggested that melatonin is a promising supplementary component in chemotherapy which allows the therapeutic doses of anticancer drugs to be reduced, minimizing their side-effects. [Read the Full Post]

Cell-based assay system for high-throughput screening of anti-photo-aging agents in fibroblast transfectants

0 | Jan 03 2019

Lee S et al. indicated sclareol attenuated UVB-induced photo-aging by an increase in collagen synthesis and decrease in MMP-1 activity. [Read the Full Post]

PPARβ/δ, a Novel Regulator for Vascular Smooth Muscle Cells Phenotypic Modulation and Vascular Remodeling after Subarachnoid Hemorrhage in Rats

426 | Dec 27 2018

Zhang H et al. identified PPARβ/δ as a useful regulator for VSMC phenotypic switch and vascular remodeling following SAH, providing novel insights into the therapeutic strategies of delayed cerebral ischemia. [Read the Full Post]

The antibiotic polymyxin B exhibits novel antifungal activity against Fusarium species

0 | Dec 23 2018

Hsu LH et al. found that PMB was fungicidal against all 12 Fusarium strains, with minimum fungicidal concentrations of 32 µg/mL or 64 µg/mL for most strains tested, as evidenced by broth dilution, methylene blue staining and XTT reduction assays. PMB can reduce the germination rates of conidia, but not chlamydospores, and can cause defects in cell membrane integrity in Fusarium strains. [Read the Full Post]

Cell-based assay system for high-throughput screening of anti-photo-aging agents in fibroblast transfectants

0 | Dec 21 2018

Lee S et al. revealed that CCN1-GFs treated with sclareol showed decreased levels of UVB-induced CCN1 expression. [Read the Full Post]

Microengineered cultures containing human hepatic stellate cells and hepatocytes for drug development

192 | Dec 16 2018

Davidson MD et al. found that NADPH oxidase (NOX) inhibition and farnesoid X receptor (FXR) activation using clinically relevant drugs alleviated hepatic dysfunctions in MPTCs. In conclusion, MPTCs recapitulate symptoms of NASH- and early fibrosis-like dysfunctions in PHHs and have utility for drug discovery in this space. [Read the Full Post]

FAM83A is amplified and promotes cancer stem cell-like traits and chemoresistance in pancreatic cancer

392 | Dec 15 2018

Chen S et al. indicated that FAM83A has a vital oncogenic role to promote pancreatic cancer progression and may represent a potential clinical target. [Read the Full Post]

Heme oxygenase-1 mitigates ferroptosis in renal proximal tubule cells

182 | Dec 13 2018

Adedoyin O et al. demonstrated an important antiferroptotic role of HO-1 in renal epithelial cells. [Read the Full Post]

PPARβ/δ activation protects against corticosterone-induced ER stress in astrocytes by inhibiting the CpG hypermethylation of microRNA-181a

385 | Dec 10 2018

Ji J et al. suggested that PPARβ/δ activation in astrocytes might be a promising target for regulating ER stress-induced astrocytic injury. [Read the Full Post]

A sensitive virus yield assay for evaluation of Antivirals against Zika Virus

0 | Nov 26 2018

Goebel S et al. indicated that due to reproducible assay performance, qPCR associated higher sensitivity and short duration of the assay time, this novel cell based assay will be very useful for confirming the activity of antivirals against ZIKV. [Read the Full Post]

Loss-of-function screens of druggable targetome against cancer stem-like cells

0 | Nov 24 2018

SiRNAs that selectively reduced CSLC only were found to target genes for cholesterol and unsaturated fatty acid synthesis. [Read the Full Post]

N-3 polyunsaturated fatty acids increase hepatic fibroblast growth factor 21 sensitivity via a PPAR-γ-β-klotho pathway

0 | Nov 15 2018

Yang W et al. indicated n-3 PUFAs increase hepatic FGF21 sensitivity and β-klotho expression probably through a PPAR-γ-dependent mechanism, and may thereby exert hepatic beneficial effects on lipid metabolism. [Read the Full Post]

Identification of the Serine Biosynthesis Pathway as a Critical Component of BRAF Inhibitor Resistance of Melanoma, Pancreatic, and Non-Small Cell Lung Cancer Cells

225 | Nov 08 2018

The novel aspects of this study are the direct identification of serine biosynthesis as a critical mechanism of BRAF V600E inhibitor resistance and the first successful example of using gemcitabine + BRAFis in combination to kill previously drug-resistant cancer cells, creating the translational potential of pretreatment with gemcitabine prior to BRAFi treatment of tumor cells to reverse resistance within the mutational profile and the WT. [Read the Full Post]

FANCD2 protects against bone marrow injury from ferroptosis

221 | Oct 27 2018

Song X et al. indicate that FANCD2 plays a novel role in the negative regulation of ferroptosis. [Read the Full Post]

Btk inhibition treats TLR7/IFN driven murine lupus

252 | Oct 23 2018

Bender AT et al. provided translational insight into how Btk inhibition may provide benefit to a variety of SLE patients by affecting both BCR and FcR signaling. [Read the Full Post]

A sensitive virus yield assay for evaluation of Antivirals against Zika Virus

320 | Oct 15 2018

Goebel S et al. showed qPCR associated higher sensitivity and short duration of the assay time, this novel cell based assay will be very useful for confirming the activity of antivirals against ZIKV. [Read the Full Post]

A multi-targeted liquid chromatography-mass spectrometry screening procedure for the detection in human urine of drugs non-prohibited in sport commonly used by the athletes

341 | Oct 09 2018

Mazzarino M et al. indicated this work presents an analytical method for the simultaneous analysis in human urine of 38 pharmacologically active compounds (19 benzodiazepine-like substances, 7 selective serotonin reuptake inhibitors, 4 azole antifungal drugs, 5 inhibitors of the phosphodiesterases type 4 and 3 inhibitors of the phosphodiesterase type 5) by liquid-chromatography coupled with tandem mass spectrometry. [Read the Full Post]

The phosphodiesterase 4 inhibitor roflumilast augments the Th17-promoting capability of dendritic cells by enhancing IL-23 production, and impairs their T cell stimulatory activity due to elevated IL-10

202 | Oct 08 2018

Bros M et al. suggested that PDE4 inhibitors aside from their broad overall anti-inflammatory effects may enhance the Th17-polarizing capacity in DCs as an unwanted side effect. [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

1453 | 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]

Targeting the epigenome: Screening bioactive compounds that regulate histone deacetylase activity

323 | Sep 26 2018

Godoy LD et al. provided the first step in identifying multiple bioactive compound HDAC inhibitors. Taken together, this report sets the stage for future exploration of these bioactive compounds as epigenetic regulators to potentially ameliorate chronic disease. [Read the Full Post]

Androgen Deprivation Followed by Acute Androgen Stimulation Selectively Sensitizes AR-Positive Prostate Cancer Cells to Ionizing Radiation

322 | Sep 22 2018

Hedayati M et al. suggested a potential cooperative effect and improved tumor growth delay with androgen-induced DSBs and radiation with implications for improving the therapeutic index of prostate cancer radiation therapy. [Read the Full Post]

Short-term high-fat feeding induces islet macrophage infiltration and β-cell replication independently of insulin resistance in mice

268 | Sep 21 2018

Woodland DC et al. suggested the existence of MΦ-mediated mechanisms in β-cell replication that are independent of insulin resistance. [Read the Full Post]

Neuregulin 1-activated ERBB4 interacts with YAP to induce Hippo pathway target genes and promote cell migration

290 | Sep 21 2018

Haskins JW et al. suggested that NRG1-ERBB4-YAP signaling contributes to the aggressive behavior of tumor cells. [Read the Full Post]

Integrated analysis of transcriptomes of cancer cell lines and patient samples reveals STK11/LKB1-driven regulation of cAMP phosphodiesterase-4D

262 | Sep 20 2018

He N et al. showed that multidimensional analysis of a well-characterized large-scale panel of cancer cell lines provides unprecedented opportunities for the identification of unexpected oncogenic mechanisms and mutation-specific drug targets. [Read the Full Post]

SIRT1 prevents hyperuricemia via the PGC-1α/PPARγ-ABCG2 pathway

0 | Sep 20 2018

Wang J et al. demonstrated that SIRT1 and its activator, RSV, have clear anti-hyperuricemia functions in this mouse model. [Read the Full Post]

Kaempferol suppresses lipid accumulation by inhibiting early adipogenesis in 3T3-L1 cells and zebrafish

446 | Sep 16 2018

Lee YJ et al. indicated that kaempferol might have an anti-obesity effect by regulating lipid metabolism. [Read the Full Post]

Luteinizing Hormone Causes Phosphorylation and Activation of the cGMP Phosphodiesterase PDE5 in Rat Ovarian Follicles, Contributing, Together with PDE1 Activity, to the Resumption of Meiosis.

261 | Sep 15 2018

Egbert JR et al. showed that activities of both PDE5 and PDE1 contribute to the LH-induced resumption of meiosis in rat oocytes, and that phosphorylation and activation of PDE5 is a regulatory mechanism. [Read the Full Post]

The LXR ligand GW3965 inhibits Newcastle disease virus infection by affecting cholesterol homeostasis

296 | Sep 13 2018

Sheng XX et al. suggested that GW3965 inhibits NDV infection, probably by affecting cholesterol homeostasis. [Read the Full Post]

Resveratrol provides neuroprotection by inhibiting phosphodiesterases and regulating the cAMP/AMPK/SIRT1 pathway after stroke in rats

373 | Sep 10 2018

Wan D et al. indicated that resveratrol provides neuroprotection by inhibiting PDEs and regulating the cAMP/AMPK/SIRT1 pathway, which reduces ATP energy consumption during ischemia. [Read the Full Post]

The anti-inflammatory effects of Morin hydrate in atherosclerosis is associated with autophagy induction through cAMP signaling

318 | Sep 10 2018

Zhou Y et al. suggested that anti-AS and anti-inflammatory effects of MO are largely associated with its induction of autophagy through stimulation of cAMP-PKA-AMPK-SIRT1 signaling pathway. [Read the Full Post]

The antibiotic polymyxin B exhibits novel antifungal activity against Fusarium species

338 | Aug 31 2018

Hsu LH et al. indicated evolutionary divergence of mechanisms between yeast pathogens and the filamentous fungus Fusarium. [Read the Full Post]

A novel, rapid method to compare the therapeutic windows of oral anticoagulants using the Hill coefficient

0 | Aug 27 2018

Chang JB et al. showed a significant variation among the Hill coefficients, suggesting a similar variation in therapeutic windows among anticoagulants in our assay. [Read the Full Post]

A High Throughput Phenotypic Screening reveals compounds that counteract premature osteogenic differentiation of HGPS iPS-derived mesenchymal stem cells

380 | Aug 07 2018

Lo Cicero A et al. highlight the potential of high-throughput drug screening using HGPS iPS-derived cells, in order to find therapeutic compounds for HGPS and, potentially, for other aging-related disorders. [Read the Full Post]

ICAM-1-Targeted Liposomes Loaded with Liver X Receptor Agonists Suppress PDGF-Induced Proliferation of Vascular Smooth Muscle Cells

388 | Jul 16 2018

Huang X et al. identified anti-ICAM-T0901317 liposomes as a promising nanotherapeutic approach to overcome VSMC proliferation during atherosclerosis progression. [Read the Full Post]

Ferroptosis is an autophagic cell death process

415 | Jul 12 2018

Gao M et al. indicated that ferroptosis is an autophagic cell death process, and NCOA4-mediated ferritinophagy supports ferroptosis by controlling cellular iron homeostasis. [Read the Full Post]

Inhibiting GLUT-1 expression and PI3K/Akt signaling using apigenin improves the radiosensitivity of laryngeal carcinoma in vivo

385 | Jun 19 2018

Bao YY et al. suggested that the effects of apigenin on inhibiting xenograft growth and enhancing xenograft radiosensitivity may be associated with suppressing the expression of GLUT-1 via the PI3K/Akt pathway. In addition, apigenin may enhance the effects of GLUT-1 AS-ODNs via the same mechanism. [Read the Full Post]

N-3 polyunsaturated fatty acids increase hepatic fibroblast growth factor 21 sensitivity via a PPAR-γ-β-klotho pathway

1135 | Jun 11 2018

Yang W et al. indicated n-3 PUFAs increase hepatic FGF21 sensitivity and β-klotho expression probably through a PPAR-γ-dependent mechanism, and may thereby exert hepatic beneficial effects on lipid metabolism. [Read the Full Post]

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

712 | 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]

A screening assay for the identification of host cell requirements and antiviral targets for hepatitis D virus infection

450 | Jun 08 2018

Buchmann B et al. provided a potentially useful tool to screen for substances with anti-HDV activity and novel insights into interactions between HDV replication and the human kinome. [Read the Full Post]

Androgen deprivation therapy sensitizes triple negative breast cancer cells to immune-mediated lysis through androgen receptor independent modulation of osteoprotegerin

447 | May 22 2018

Kwilas AR et al. supported the consideration of AR inhibition therapy for the treatment of AR- TNBC, especially in combination with cancer immunotherapy, providing a potential novel therapeutic option for select patients. [Read the Full Post]

Resveratrol Attenuates Aβ25-35 Caused Neurotoxicity by Inducing Autophagy Through the TyrRS-PARP1-SIRT1 Signaling Pathway.

411 | May 19 2018

Deng H et al. found that RSV attenuated neurotoxicity caused by Aβ25-35 through inducing autophagy in PC12 cells, and the autophagy was partially mediated via activation of the TyrRS-PARP1-SIRT1 signaling pathway. [Read the Full Post]

Dihydroartemisinin restricts hepatic stellate cell contraction via an FXR-S1PR2-dependent mechanism

419 | May 09 2018

Xu W et al. suggested that DHA could restrict HSC contraction through modulating FXR/S1PR2 pathway-mediated Ca(2+) -dependent and Ca(2+) -sensitization signaling. Our discoveries make DHA a potential candidate for portal hypertension. [Read the Full Post]

PPARβ/δ activation protects against corticosterone-induced ER stress in astrocytes by inhibiting the CpG hypermethylation of microRNA-181a

1030 | May 06 2018

Ji J et al. suggested that PPARβ/δ activation in astrocytes might be a promising target for regulating ER stress-induced astrocytic injury. [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

805 | 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]

Abrogating cholesterol esterification suppresses growth and metastasis of pancreatic cancer

464 | Apr 30 2018

Li J et al. demonstrated a new strategy for treating metastatic pancreatic cancer by inhibiting cholesterol esterification. [Read the Full Post]

PPARβ/δ activation protects against corticosterone-induced ER stress in astrocytes by inhibiting the CpG hypermethylation of microRNA-181a

402 | Apr 27 2018

Ji J et al. suggested that PPARβ/δ activation in astrocytes might be a promising target for regulating ER stress-induced astrocytic injury. [Read the Full Post]

Activation of carbonic anhydrase IX by alternatively spliced tissue factor under late-stage tumor conditions.

416 | Apr 21 2018

Ramchandani D et al. found that CAIX is a novel downstream mediator of asTF in pancreatic cancer, particularly under hypoxic conditions that model late-stage tumor microenvironment. [Read the Full Post]

Tanshinone I inhibits tumor angiogenesis by reducing Stat3 phosphorylation at Tyr705 and hypoxia-induced HIF-1α accumulation in both endothelial and tumor cells

383 | Apr 12 2018

Wang Y et al. revealed unique characteristics of tanshinone-1 and its improved derivatives as promising angiogenesis inhibitors. [Read the Full Post]

Neuroprotective effects of piperine on the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's disease mouse model.

0 | Apr 06 2018

Yang W et al. showed that piperine exerts a protective effect on dopaminergic neurons via antioxidant, anti-apoptotic, and anti-inflammatory mechanisms in an MPTP-induced mouse model of PD [Read the Full Post]

Tsc1 expression by dendritic cells is required to preserve T-cell homeostasis and response

0 | Mar 28 2018

Luo Y et al. identified Tsc1 as a crucial signaling checkpoint in DCs essential for preserving T-cell homeostasis and response. [Read the Full Post]

Significance of alpha smooth muscle actin expression in traumatic painful neuromas: a pilot study in rats

451 | Mar 28 2018

Weng W et al. provided new insights into the development of new treatment modalities for the management of intractable painful neuromas. [Read the Full Post]

HSPA5 Regulates Ferroptotic Cell Death in Cancer Cells

0 | Mar 07 2018

Zhu S et al. identified a novel role of HSPA5 in ferroptosis and suggest a potential therapeutic strategy for overcoming gemcitabine resistance. [Read the Full Post]

Characterization of osimertinib (AZD9291)-resistant non-small cell lung cancer NCI-H1975/OSIR cell line

794 | Mar 03 2018

Tang ZH et al. showed that EGFR could pose as one of the OSI-resistant mechanisms and navitoclax might be the candidate drug for OSI-resistant NSCLC patients. [Read the Full Post]

Loss-of-function screens of druggable targetome against cancer stem-like cells

690 | Feb 19 2018

Song M, et al. provided a useful resource that can be exploited for the selective elimination of CSLCs. [Read the Full Post]

Dihydroartemisinin protects against alcoholic liver injury through alleviating hepatocyte steatosis in a farnesoid X receptor-dependent manner

520 | Feb 15 2018

Xu W et al. indicated DHA significantly improved alcoholic liver injury by inhibiting hepatic steatosis, which was dependent on its activation of FXR in hepatocytes. [Read the Full Post]

Histochemical examination of the effects of high-dose 1,25(OH)2D3 on bone remodeling in young growing rats

467 | Feb 13 2018

Sun J et al. suggested that long-term use of physiologically-high dose calcitriol may result in bone loss through RANKL/RANK/osteoprotegerin and EphrinB2-EphB4 signaling pathways, and that these negative effects could continue after drug withdrawal. Therefore, optimal limits for vitamin D administration need to be established for children and adolescents. [Read the Full Post]

Fasting-induced hormonal regulation of lysosomal function.

0 | Feb 12 2018

Chen L et al. indicated the FGF21-TFEB signaling axis links lysosome homeostasis with extracellular hormonal signaling to orchestrate lipid metabolism during fasting. [Read the Full Post]

FOXM1 evokes 5-fluorouracil resistance in colorectal cancer depending on ABCC10

461 | Feb 07 2018

Xie T et al. suggested that FOXM1/ABCC10 axis may serve as a potential therapeutic target for 5-FU resistance in CRC patients. [Read the Full Post]

Ablation of ferroptosis regulator glutathione peroxidase 4 in forebrain neurons promotes cognitive impairment and neurodegeneration

563 | Jan 26 2018

Hambright WS et al. suggested that ferroptosis may be an important neurodegenerative mechanism in diseases such as AD. [Read the Full Post]

Efficacy of continuous EGFR-inhibition and role of Hedgehog in EGFR acquired resistance in human lung cancer cells with activating mutation of EGFR

0 | Jan 20 2018

Della Corte CM et al. found that EGFR-mutant NSCLC can benefit from continuous treatment with EGFR-inhibitors, indepenently from mechanisms of resistance [Read the Full Post]

Epigallocatechin gallate reverses cTnI-low expression-induced age-related heart diastolic dysfunction through histone acetylation modification

1672 | Jan 11 2018

Pan B et al. provided new insights into histone acetylation mechanisms of EGCG treatment that may contribute to the prevention of CDD in ageing populations. [Read the Full Post]

Simvastatin augments revascularization and reperfusion in a murine model of hind limb ischemia - Multimodal imaging assessment

510 | Jan 09 2018

Goggi JL et al. identified using 99mTc-RGD SPECT, which displays significant increases in retention before macrovascular volume changes are measureable with MRI. [Read the Full Post]

BCL6 modulation of acute lymphoblastic leukemia response to chemotherapy

489 | Dec 27 2017

Slone WL et al. suggested that BCL6 is one factor, modulated by microenvironment derived cues that may contribute to regulation of ALL therapeutic response. [Read the Full Post]

CK2α' Drives Lung Cancer Metastasis by Targeting BRMS1 Nuclear Export and Degradation

0 | Dec 02 2017

Liu Y et al. identified a therapeutically exploitable posttranslational mechanism by which CK2α-mediated degradation of BRMS1 promotes metastases in lung cancer. [Read the Full Post]

HSP90 activity is required for MLKL oligomerisation and membrane translocation and the induction of necroptotic cell death

1142 | 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

1380 | 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

1175 | 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]

HSPA5 Regulates Ferroptotic Cell Death in Cancer Cells

646 | Oct 23 2017

Zhu S et al. identified a novel role of HSPA5 in ferroptosis and suggest a potential therapeutic strategy for overcoming gemcitabine resistance. [Read the Full Post]

Canonical hedgehog signalling regulates hepatic stellate cell-mediated angiogenesis in liver fibrosis

1352 | 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]

Regulation of the Nampt-mediated NAD salvage pathway and its therapeutic implications in pancreatic cancer

676 | Oct 10 2017

Ju HQ et al. suggested that Nampt inhibition may override gemcitabine resistance by decreasing the NAD level and suppressing glycolytic activity, warranting further clinical investigation for pancreatic cancer treatment. [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

1291 | 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]

Harmine Induces Adipocyte Thermogenesis through RAC1-MEK-ERK-CHD4 Axis

863 | Sep 22 2017

Nie T et al. reveal a new application of harmine in combating obesity via this off-target effect in adipocytes. [Read the Full Post]

A Schisandra-Derived Compound Schizandronic Acid Inhibits Entry of Pan-HCV Genotypes into Human Hepatocytes

759 | Sep 21 2017

Qian XJ et al. suggested that SZA potently inhibited pan-HCV genotype entry into hepatoma cells and primary human hepatocytes without interfering virus binding on cell surface or internalization. However, virion-cell fusion process was impaired in the presence of SZA, along with the increased host membrane fluidity. We also found that SZA inhibited the spread of HCV to the neighboring cells, and combinations of SZA with interferon or telaprevir resulted in additive synergistic effect against HCV. Additionally, SZA diminished the establishment of HCV infection in vivo. The SZA target is different from conventional direct-acting antiviral agents, therefore, SZA is a potential therapeutic compound for the development of effective HCV entry inhibitors, especially for patients who need to prevent HCV reinfection during the course of liver transplantations. [Read the Full Post]

Hyperthermia reduces migration of osteosarcoma by suppression of autocrine motility factor

1349 | 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]

Potentiating the antitumour response of CD8(+) T cells by modulating cholesterol metabolism

974 | Jun 21 2017

Yang W, et al. used the ACAT inhibitor avasimibe, which was previously tested in clinical trials for treating atherosclerosis and showed a good human safety profile, to treat melanoma in mice and observed a good antitumour effect. [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]

Phosphodiesterase 5/protein kinase G signal governs stemness of prostate cancer stem cells through Hippo pathway

795 | Jun 01 2017

Liu N et al. suggested that PDE5 inhibitors in combination with chemotherapeutic agents could effectively prevent initiation, metastasis, and relapse of prostate cancer. [Read the Full Post]

Erastin Disrupts Mitochondrial Permeability Transition Pore (mPTP) and Induces Apoptotic Death of Colorectal Cancer Cells

0 | May 25 2017

Huo H et al. found that erastin is cytotoxic and pro-apoptotic to colorectal cancer cells. [Read the Full Post]

The effect of hyperlipidemia on the pharmacokinetics, hepatic and pulmonary uptake of posaconazole in rat

0 | May 20 2017

Khalil HA et al. induced lipoprotein level elevation caused alterations in the PSZ pharmacokinetics and decreased its hepatic and pulmonary uptake. [Read the Full Post]

Neuritin Mediates Activity-Dependent Axonal Branch Formation in Part via FGF Signaling.

3170 | May 07 2017

Shimada T et al suggested that neuritin and FGF cooperate in inducing mossy fiber sprouting through FGF signaling. Together, these results suggest that FGF and neuritin-mediated axonal branch induction are involved in the aggravation of epilepsy. [Read the Full Post]

Specificity of anti-prostate cancer CYP17A1 inhibitors on androgen biosynthesis

846 | Apr 08 2017

Udhane SS et al. concluded that orteronel is a highly specific inhibitor of 17,20 lyase activity. [Read the Full Post]

A chemical with proven clinical safety rescues Down-syndrome-related phenotypes in through DYRK1A inhibition

1707 | Apr 06 2017

Kim H et al. demonstrated that CX-4945 is a potent DYRK1A inhibitor and also suggested that it has therapeutic potential for DYRK1A-associated diseases. [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]

The-cyclic-GMP-protein-kinase-G-pathway-as-a-therapeutic-target-in-head-and-neck-squamous-cell-carcinoma

851 | Mar 19 2017

Tuttle TR et al found that Tadalafil substantially reduced the growth of CAL27-derived tumors in athymic mice. Several drugs which either activate sGC or inhibit PDE5 are approved for treatment of nonmalignant conditions. These drugs could be repurposed as novel and effective therapeutics in patients with head and neck cancer. [Read the Full Post]

Pioglitazone Suppresses CXCR7 Expression To Inhibit Human Macrophage Chemotaxis through Peroxisome Proliferator-Activated Receptor γ

1804 | Mar 16 2017

Zhao D et al found that pioglitazone suppresses CXCR7 expression to inhibit human macrophage chemotaxis through PPARγ. [Read the Full Post]

Heat shock protein 90 inhibitors induce functional inhibition of human natural killer cells in a dose-dependent manner

1500 | 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]

Metallothionein-1G facilitates sorafenib resistance through inhibition of ferroptosis

1308 | Mar 10 2017

Sun X et al. found that knockdown of MT-1G by RNA interference increases glutathione depletion and lipid peroxidation, which contributes to sorafenib-induced ferroptosis. [Read the Full Post]

Identification of baicalein as a ferroptosis inhibitor by natural product library screening

1022 | Mar 10 2017

Xie Y et al. found that baicalein enhances cellular anti-ferroptosis capacity and could be a potential therapeutic agent for ferroptosis-associated tissue injury. [Read the Full Post]

SIRT1 prevents hyperuricemia via the PGC-1α/PPARγ-ABCG2 pathway

903 | Mar 09 2017

Wang J et al. found that one possible mechanism is the activation of ABCG2 in the ileum through the PGC-1α/PPARγ pathway. [Read the Full Post]

In vitro antifungal synergy between amphiphilic aminoglycoside K20 and azoles against Candida species and Cryptococcus neoformans

0 | Mar 07 2017

Shrestha SK et al. suggested that combinations of K20 and azoles offer a possible strategy for developing therapies against candidiasis. [Read the Full Post]

Endothelial Cell Apoptosis Induces TGF-b Signaling-Dependent Host Endothelial–Mesenchymal Transition to Promote Transplant Arteriosclerosis

1919 | Mar 05 2017

Li J et al. suggested that allograft EC apoptosis induced recipient endothelial-mesenchymal (smooth muscle) transition via TGF-β signaling, resulting in recipient EC-derived SMC accumulation as a major mechanism of vascular remodeling during TA. [Read the Full Post]

Activation of the p62-Keap1-NRF2 Pathway Protects Against Ferroptosis in Hepatocellular Carcinoma Cells

0 | Feb 11 2017

Sun X, et al.'s findings demonstrate novel molecular mechanisms and signaling pathways of ferroptosis; the status of NRF2 is a key factor that determines the therapeutic response to ferroptosis-targeted therapies in HCC cells. [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

3469 | 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]

Pioglitazone Suppresses CXCR7 Expression To Inhibit Human Macrophage Chemotaxis through Peroxisome Proliferator-Activated Receptor γ

1137 | Jan 23 2017

Zhao D, et al.'s data demonstrate that pioglitazone suppresses CXCR7 expression to inhibit human macrophage chemotaxis through PPARγ. [Read the Full Post]

Heat shock protein 90 inhibitors induce functional inhibition of human natural killer cells in a dose-dependent manner

1619 | 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]

In vitro antifungal synergy between amphiphilic aminoglycoside K20 and azoles against Candida species and Cryptococcus neoformans

1147 | Jan 18 2017

Shrestha SK et al. suggested that combinations of K20 and azoles offer a possible strategy for developing therapies against candidiasis. [Read the Full Post]

Nitric oxide plays a dual role in the oxidative injury of cultured rat microglia but not astroglia

1926 | 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]

Erastin Disrupts Mitochondrial Permeability Transition Pore (mPTP) and Induces Apoptotic Death of Colorectal Cancer Cells

1360 | Oct 24 2016

Huo H et al. demonstrated that erastin is cytotoxic and pro-apoptotic to colorectal cancer cells. [Read the Full Post]

The cyclic GMP/protein kinase G pathway as a therapeutic target in head and neck squamous cell carcinoma

0 | Sep 04 2016

Tuttle TR, et al. found that several drugs which either activate sGC or inhibit PDE5 are approved for treatment of nonmalignant conditions. These drugs could be repurposed as novel and effective therapeutics in patients with head and neck cancer. [Read the Full Post]

Activation of the p62-Keap1-NRF2 pathway protects against ferroptosis in hepatocellular carcinoma cells

2461 | Aug 31 2016

Sun X, et al. demonstrated novel molecular mechanisms and signaling pathways of ferroptosis; the status of NRF2 is a key factor that determines the therapeutic response to ferroptosis-targeted therapies in HCC cells. [Read the Full Post]

The role of heat shock protein beta-1 in erastin-induced ferroptosis

3752 | Mar 09 2015

Sun et al. found heat shock protein beta-1 (HSPB1) as a key negative mediator of ferroptotic cancer cell death. [Read the Full Post]

An unusual mechanism of ERBB4 in regulating tumor related gene expression

8179 | Jan 06 2015

Haskins et al. found ERBB4 activated the transcriptional coactivator YAP by binding to its ligand neuregulin 1 (NRG1), to regulate gene expression of cancer cells. [Read the Full Post]

ERK/Cdk5 axis regulates diabetes-related PPARγ phosphorylation

6893 | Nov 21 2014

Recently, Banks et al. discovered that ERK/Cdk5 axis is involved in regulation PPARγ activities, and the inhibition of ERK and MEK leads to the improvement of insulin resistance. [Read the Full Post]

Gsk256066 is a potent and selective inhaled PDE4 inhibitor

2358 | Jan 24 2014

GSK256066 is a selective PDE4B(equal affinity to isoforms A-D) inhibitor with IC50 of 3.2 pM, >380,000-fold selectivity versus PDE1/2/3/5/6 and >2500-fold selectivity against PDE4B versus PDE7. [Read the Full Post]

Learn about the prescription medication Methazolamide

2421 | May 26 2013

Methazolamide is a carbonic anhydrase inhibitor with Ki of 50 nM, 14 nM and 36 nM for hCA I, hCA II and bCA IV isoforms, respectively. [Read the Full Post]

Effects of oral administration of methazolamide on intraocular pressure

2336 | May 22 2013

In vitro characterization of the erythrocyte distribution of methazolamide: a model of erythrocyte transport and binding kinetics [Read the Full Post]

MDV3100 was found clinically active for metastatic

2555 | Apr 18 2013

MDV3100 is an androgen receptor antagonist drug developed by the pharmaceutical company Medivation for the treatment of metastatic castration-resistant prostate cancer. [Read the Full Post]

Enzalutamide is an androgen receptor inhibitor

2049 | Feb 27 2013

Little is known of pathways involved in upstream control of Notch1 gene expression and activity in keratinocytes, and mammalian cells in general. To address this issue we undertook a chemical genetics approach. Rather than screening a large collection of unknown chemicals, enzalutamide we chose a library of 489 compounds [Read the Full Post]

ONCOGENES AND HSP90 INHIBITORS

4479 | 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

4747 | 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

4501 | 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

3779 | 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]

TOSEDOSTAT: INHIBITING AMINOPEPTIDASES IN CANCERS

2758 | Mar 18 2012

AMINOPEPTIDASES AND THEIR INHIBITION: Aminopeptidases catalyze the cleavage of amino acids of proteins or peptide substrates. Such enzymes are zinc dependant and located throughout most mammalian tissue and in certain plant extracts. They are essential for many cellular maintenance functions and are release systemically from the small intestine. Since these enzymes act by hydrolysis amino acids located at the amino groups of terminal proteins inhibition of their processes would affect cell proliferation, secretion, invasion and angiogenesis. Small molecule inhibitors for the inhibition of aminopeptidases have been developed for oncological use. CHR-2797 is a pro-drug for an aminopeptidase inhibitor that is marketed by Chroma Therapeutics under the trade name of Tosedostat. Tosedostat aminopeptidase inhibitor under goes cellular modulation to the active metabolite (CHR79888) via hydrolysis of a methoxy group. This metabolite is poorly membrane permeable, resulting in cellular accumulation. In animal models Toseostad has proved to be a significant inhibitor of proliferation and has demonstrated anti-angiogenic activity. [Read the Full Post]

Roles of Hsp90 in wound healing and cancer

5014 | 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.

3722 | 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]