Category
- PI3K/Akt/mTOR
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Archives
Transmembrane Transporters
Oncogenic Chromatin Modifier KAT2A Activates MCT1 to Drive the Glycolytic Process and Tumor Progression in Renal Cell Carcinoma
3 | Jul 27 2021
Yuanyuan Guo et al. proposed that MCT1 inhibitor (AZD3965) was useful for suppressing RCC. [Read the Full Post]
Mechanism of Ferroptosis and Its Role in Type 2 Diabetes Mellitus
3 | Jul 15 2021
Wenxin Sha et al. summarized the mechanism of ferroptosis and especially its association with type 2 diabetes mellitus (T2DM). [Read the Full Post]
Detection of autophagic flux in primary cerebral cortical neurons after oxygen glucose deprivation/reperfusion (OGD/R) using various methods
8 | Jul 12 2021
Lei Zhang et al. showed that different methods and indicators could be used to monitor different stages of autophagy. [Read the Full Post]
Inhibition of DNA-PK with AZD7648 Sensitizes Tumor Cells to Radiotherapy and Induces Type I IFN-Dependent Durable Tumor Control
7 | Jun 22 2021
Kyoko Nakamura et al. found that blocking the NHEJ DNA repair pathway with AZD7648 in combination with RT leaded to durable immune-mediated tumor control. [Read the Full Post]
Partial Rescue of F508del-CFTR Stability and Trafficking Defects by Double Corrector Treatment
7 | Jun 21 2021
Valeria Capurro et al. thought that it was still possible to further improve mutant CFTR rescue with the development of corrector combinations having maximal effects on mutant CFTR structural and functional properties. [Read the Full Post]
GDI2 is a target of paclitaxel that affects tumorigenesis of prostate cancer via the p75NTR signaling pathway
10 | May 31 2021
Chi Liu et al. found that knocking down of GDI2 inhibited cell proliferation and promoted cell apoptosis via the p75NTR signaling pathway in prostate cancer. [Read the Full Post]
Nonsense-mediated mRNA decay efficiency influences bleeding severity in ITGA2B c.2659C > T (p.Q887X) knock-in mice
12 | May 10 2021
Zhanli Xie et al. found that NMD efficiency potentially influenced bleeding severity in ITGA2B c.2659C > T (p.Q887X) KI mice. [Read the Full Post]
High BRCA2 Gene Expression is Associated with Aggressive and Highly Proliferative Breast Cancer
11 | May 10 2021
Vikas Satyananda et al. thought that BRCA2 gene expression might become a candidate marker for aggressive biology and to tailor specific treatment strategies in the future. [Read the Full Post]
Involvement of GLUT1 and GLUT3 in the growth of canine melanoma cells
19 | Apr 25 2021
Yoko Suwabe et al. suggested that glucose uptake via GLUT1 and GLUT3 played a crucial role for the growth of canine melanoma cells. [Read the Full Post]
A covalent p97/VCP ATPase inhibitor can overcome resistance to CB-5083 and NMS-873 in colorectal cancer cells
17 | Mar 26 2021
Gang Zhang et al. identified and characterized PPA as a selective covalent p97 inhibitor, which would allow future exploration to improve the potency of p97 inhibitors with different mechanisms of action. [Read the Full Post]
The effect of ivermectin alone and in combination with cobicistat or elacridar in experimental Schistosoma mansoni infection in mice
21 | Mar 10 2021
Belén Vicente et al. thought that even in the presence of pharmacological inhibition of P-glycoprotein or cytochrome P450 3A, did not result in effective prophylaxis for S. mansoni infection in an experimental murine model. [Read the Full Post]
Optimization of dose and route of administration of the P-glycoprotein inhibitor, valspodar (PSC-833) and the P-glycoprotein and breast cancer resistance protein dual-inhibitor, elacridar (GF120918) as dual infusion in rats
24 | Mar 09 2021
Christopher Rowbottom rt al. demonstrated that doses greater than 0.9 mg/hr/kg valspodar and 8.9 mg/hr/kg elacridar were sufficient to inhibit P-gp- and BCRP-mediated efflux at the blood-brain barrier in rats without any tolerability issues. [Read the Full Post]
Transcriptomic analysis of CFTR-impaired endothelial cells reveals a pro-inflammatory phenotype
28 | Feb 01 2021
Mathias Declercq et al. thought that normalisation of vascular inflammation might be a novel therapeutic strategy to ameliorate the disease severity of CF. [Read the Full Post]
Relation of Metal-Binding Property and Selective Toxicity of 8-Hydroxyquinoline Derived Mannich Bases Targeting Multidrug Resistant Cancer Cells
30 | Jan 31 2021
Veronika F S Pape et al. showed that the MDR-selective anticancer activity of the studied 8-hydroxyquinoline derived Mannich bases was associated with the iron deprivation of MDR cells and the preferential formation of redox-active copper(II) complexes, which underwent intracellular redox-cycling to induce oxidative stress. [Read the Full Post]
Repurposing FDA approved drugs inhibiting mitochondrial function for targeting glioma-stem like cells
29 | Jan 11 2021
Sandipan Datta et al. demonstrated that FDA-approved mitochondrial inhibitors induced GSC-selective cytotoxicity, and targeting mitochondrial function could present a potential therapeutic option for GBM treatment. [Read the Full Post]
Real-World Safety of CFTR Modulators in the Treatment of Cystic Fibrosis: A Systematic Review
31 | Jan 05 2021
Renée V E Dagenais et al. thought that pharmacists played a key role in the safe initiation and monitoring of people with CF on CFTR modulator therapies. [Read the Full Post]
Switching between blebbing and lamellipodia depends on the degree of Nonmuscle Myosin II activity
31 | Dec 26 2020
Indranil Ghosh et al. revealed that relative activity of ROCK and MLCK, which controled both NMII's ATPase activity and filamentous property was a determining factor for a cell to exhibit blebbing or lamellipodia. [Read the Full Post]
Empagliflozin and the Diabetic Kidney: Pathophysiological Concepts and Future Challenges
35 | Dec 16 2020
Georgios S Papaetis discussed the safety of empagliflozin therapy and its future role in order to ameliorate the global burden of CKD both in patients with and without diabetes. [Read the Full Post]
The XPO1 Inhibitor KPT-8602 Synergizes with Dexamethasone in Acute Lymphoblastic Leukemia
40 | Dec 07 2020
Delphine Verbeke et al. demonstrated that KPT-8602 enhanced the effects of dexamethasone to inhibit B-ALL and T-ALL cells via NR3C1- and E2F-mediated transcriptional complexes, allowing to achieve increased dexamethasone effects for patients. [Read the Full Post]
Melphalan and Exportin 1 Inhibitors Exert Synergistic Antitumor Effects in Preclinical Models of Human Multiple Myeloma
31 | Dec 06 2020
Joel G Turner et al. found that inhibition of exportin 1 with selinexor synergistically sensitizeed human multiple myeloma to melphalan by inhibiting Fanconi anemia pathway-mediated DNA repair. [Read the Full Post]
Small molecule inhibitors provide insights into the relevance of LAT1 and LAT2 in materno-foetal amino acid transport
43 | Nov 04 2020
Jonas Zaugg et al. thought that differential specificity of the applied inhibitors allowed for estimation of the contribution of LAT1 and LAT2 in materno-foetal AA transfer and their potential impact in pregnancy diseases associated with impaired foetal growth. [Read the Full Post]
An integrated drug repurposing strategy for the rapid identification of potential SARS-CoV-2 viral inhibitors
54 | Sep 01 2020
Alfonso Trezza et al. showed that Simeprevir and Lumacaftor bound the receptor-binding domain of the Spike protein with high affinity and prevented ACE2 interaction. [Read the Full Post]
In Vitro and In Vivo Efficacy of AZD3965 and Alpha-Cyano-4-Hydroxycinnamic Acid in the Murine 4T1 Breast Tumor Model
0 | Aug 07 2020
Xiaowen Guan et al. indicated AZD3965 is a potent MCT1 inhibitor that accumulates to high concentrations in 4T1 xenograft tumors, where it increases tumor lactate concentrations and produces beneficial effects on markers of TNBC [Read the Full Post]
Repolarization of tumor infiltrating macrophages and increased survival in mouse primary CNS lymphomas after XPO1 and BTK inhibition
75 | Jul 30 2020
Isabel Jiménez et al. highlighted the pathogenic role of the innate immune microenvironment in PCNSL and provided pre-clinical evidence for the development of selinexor and ibrutinib as a new promising therapeutic option with cytotoxic and immunomodulatory potential. [Read the Full Post]
Clinical Utility of Selinexor/Dexamethasone in Patients with Relapsed or Refractory Multiple Myeloma: A Review of Current Evidence and Patient Selection
68 | Jul 30 2020
Panagiotis Malandrakis et al. showed that selinexor was a new anti-myeloma drug that seemed to be effective in patients who had no other therapeutic options, including patients who had received novel cellular therapies such as CAR-T cells. [Read the Full Post]
The impact of ivacaftor on sinonasal pathology in S1251N-mediated cystic fibrosis patients
107 | Jul 21 2020
Romee Gostelie et al. found that Ivacaftor appeared to improve sinonasal outcome parameters and thereby sinonasal health in patients with cystic fibrosis with an S1251N mutation. [Read the Full Post]
In Vitro and In Vivo Efficacy of AZD3965 and Alpha-Cyano-4-Hydroxycinnamic Acid in the Murine 4T1 Breast Tumor Model
114 | Jun 25 2020
Xiaowen Guan et al. indicated AZD3965 was a potent MCT1 inhibitor that accumulated to high concentrations in 4T1 xenograft tumors, where it increased tumor lactate concentrations and produced beneficial effects on markers of TNBC [Read the Full Post]
HMGB1-induced Aberrant Autophagy Contributes to Insulin Resistance in Granulosa Cells in PCOS
138 | Jun 04 2020
Chuyue Zhang et al. indicated that increased HMGB1 contributes to IR development in granulosa cells of PCOS patients, which was associated with exacerbation of autophagy by HMGB1. Control of HMGB1 production might be benefical for the improvement of insulin sensitivity in granulosa cells in PCOS. [Read the Full Post]
Berberine Represses Human Gastric Cancer Cell Growth in Vitro and in Vivo by Inducing Cytostatic Autophagy via Inhibition of MAPK/mTOR/p70S6K and Akt Signaling Pathways
115 | Jun 04 2020
Qiang Zhang et al. indicated that berberine repressed human gastric cancer cell growth in vitro and in vivo by inducing cytostatic autophagy via inhibition of MAPK/mTOR/p70S6K and Akt, and provided a molecular basis for the treatment of gastric cancer. [Read the Full Post]
Targeting Myosin by Blebbistatin Derivatives: Optimization and Pharmacological Potential
117 | Apr 14 2020
Rauscher AÁ et al. discussed the pharmacological perspectives of these efforts, as myosins are becoming promising drug target candidates for a variety of conditions ranging from neurodegeneration to muscle disease, wound healing, and cancer metastasis. [Read the Full Post]
How Does Empagliflozin Reduce Cardiovascular Mortality? Insights From a Mediation Analysis of the EMPA-REG OUTCOME Trial
141 | Mar 12 2020
Inzucchi SE et al. indicated in this exploratory analysis from the EMPA-REG OUTCOME trial, changes in markers of plasma volume were the most important mediators of the reduction in risk of CV death with empagliflozin versus placebo. [Read the Full Post]
The Second-Generation Exportin-1 Inhibitor KPT-8602 Demonstrates Potent Activity Against Acute Lymphoblastic Leukemia
129 | Mar 01 2020
Thomas Vercruysse et al. showed that KPT-8602 is highly specific for XPO1 inhibition and demonstrates potent anti-leukemic activity supporting clinical application of the second-generation SINE compound for the treatment of ALL. [Read the Full Post]
Nuclear-Cytoplasmic Transport Is a Therapeutic Target in Myelofibrosis
144 | Feb 28 2020
Dongqing Yan et al. implicated NCT as a potential therapeutic target in myelofibrosis and provide a rationale for clinical evaluation in ruxolitinib-exposed patients with myelofibrosis. [Read the Full Post]
JPH203, a selective L-type amino acid transporter 1 inhibitor, induces mitochondria-dependent apoptosis in Saos2 human osteosarcoma cells
149 | Jan 08 2020
Choi DW et al. suggested that the inhibition of LAT1 activity via JPH203, which may act as a potential novel anti-cancer agent, leads to apoptosis mediated by the mitochondria-dependent intrinsic apoptotic signaling pathway by inducing the intracellular depletion of neutral amino acids essential for cell growth in Saos2 human osteosarcoma cells. [Read the Full Post]
Corrector VX-809 promotes interactions between cytoplasmic loop one and the first nucleotide-binding domain of CFTR
179 | Nov 12 2019
Loo TW et al. suggested that the mechanism by which VX-809 promotes maturation and stability of CFTR is by promoting CL1/NBD1 interactions. [Read the Full Post]
KPT-330 inhibition of chromosome region maintenance 1 is cytotoxic and sensitizes chronic myeloid leukemia to Imatinib
188 | Oct 13 2019
Nie D et al. indicated that KPT-330 showed anti-leukemic activity and sensitized CML to IM in CRM1-dependent manner in vitro and in vivo. KPT-330 represents an alternative therapy for IM-refractory CML, warranting further investigation of CRM1 as therapeutic target. [Read the Full Post]
Selinexor-induced thrombocytopenia results from inhibition of thrombopoietin signaling in early megakaryopoiesis
257 | Oct 10 2019
Machlus KR et al. revealed (1) the mechanism of selinexor-induced thrombocytopenia, (2) an effective way to reverse the dose-limiting thrombocytopenia, and (3) a novel role for XPO1 in megakaryopoiesis. The improved selinexor dosing regimen described herein is crucial to help reduce thrombocytopenia in selinexor patients, allowing them to continue their course of chemotherapy and have the best chance of survival. [Read the Full Post]
Some gating potentiators, including VX-770, diminish ΔF508-CFTR functional expression
355 | Sep 29 2019
Veit G et al. indicated that VX-770 diminished the folding efficiency and the metabolic stability of ΔF508-CFTR at the endoplasmic reticulum (ER) and post-ER compartments, respectively, causing reduced cell surface ΔF508-CFTR density and function. VX-770-induced destabilization of ΔF508-CFTR was influenced by second-site suppressor mutations of the folding defect and was prevented by stabilization of the nucleotide-binding domain 1 (NBD1)-NBD2 interface. The reduced correction efficiency of ΔF508-CFTR, as well as of two other processing mutations in the presence of VX-770, suggests the need for further optimization of potentiators to maximize the clinical benefit of corrector-potentiator combination therapy in CF. [Read the Full Post]
Bafilomycin A1 disrupts autophagic flux by inhibiting both V-ATPase-dependent acidification and Ca-P60A/SERCA-dependent autophagosome-lysosome fusion
240 | Sep 07 2019
Mauvezin C et al. identified the ER-calcium ATPase Ca-P60A/dSERCA as a novel target of bafilomycin A1. Autophagosome-lysosome fusion was defective in Ca-P60A/dSERCA-depleted cells, and bafilomycin A1 induced a significant increase in cytosolic calcium concentration and disrupted Ca-P60A/SERCA-mediated fusion. Thus, bafilomycin A1 disrupts autophagic flux by independently inhibiting V-ATPase-dependent acidification and Ca-P60A/SERCA-dependent autophagosome-lysosome fusion. [Read the Full Post]
Treatment of γ-Hydroxybutyric Acid and γ-Butyrolactone Overdose with Two Potent Monocarboxylate Transporter 1 Inhibitors, AZD3965 and AR-C155858
352 | Aug 26 2019
Follman KE et al. indicated that inhibition of MCT1 is an effective treatment of GHB/GBL overdose. [Read the Full Post]
Inhibition of the amino-acid transporter LAT1 demonstrates anti-neoplastic activity in medulloblastoma
196 | Aug 10 2019
Cormerais Y et al. demonstrated that a long-term treatment with JPH203 does not lead to resistance in MB cells. Therefore, this study suggests that targeting LAT1 with JPH203 is a promising therapeutic approach for MB treatment. [Read the Full Post]
Bafilomycin A1 triggers proliferative potential of senescent cancer cells in vitro and in NOD/SCID mice
220 | Aug 01 2019
Was H et al. suggested that senescent cancer cells that appear during therapy, can be considered as dormant cells that contribute to cancer re-growth, when chemotherapeutic treatment is stopped. These data unveil new mechanisms of TIS-related cancer maintenance and re-population, triggered by a single pulse of BAF A1 treatment. [Read the Full Post]
Safety and efficacy of selinexor in relapsed or refractory multiple myeloma and Waldenstrom macroglobulinemia
339 | Mar 14 2019
Chen C et al. concluded that selinexor in combination with dexamethasone is active in heavily pretreated MM and propose a RP2D of 45 mg/m2 (80 mg) plus 20 mg dexamethasone given twice weekly. This trial was registered at clinicaltrials.gov as #NCT01607892. [Read the Full Post]
Selinexor (KPT-330) demonstrates anti-tumor efficacy in preclinical models of triple-negative breast cancer
297 | Mar 14 2019
Arango NP et al. showed that Selinexor demonstrated growth inhibition in all 14 TNBC cell lines tested; TNBC cell lines were more sensitive to selinexor (median IC50 44 nM, range 11 to 550 nM) than were estrogen receptor (ER)-positive breast cancer cell lines (median IC50 > 1000 nM, range 40 to >1000 nM; P = 0.017). In multiple TNBC cell lines, selinexor was synergistic with paclitaxel, carboplatin, eribulin, and doxorubicin in vitro. Selinexor as a single agent reduced tumor growth in vivo in four of five different TNBC PDX models, with a median tumor growth inhibition ratio (T/C: treatment/control) of 42% (range 31 to 73%) and demonstrated greater antitumor efficacy in combination with paclitaxel or eribulin (average T/C ratios of 27% and 12%, respectively). [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]
Modeling Congenital Hyperinsulinism with ABCC8-Deficient Human Embryonic Stem Cells Generated by CRISPR/Cas9
321 | Feb 12 2019
Guo D et al. found that pancreatic differentiation of ABCC8-deficient cells recapitulated the CHI disease phenotype in vitro, which represents an attractive model to further elucidate the function of SUR1 and to develop and screen for novel therapeutic drugs. [Read the Full Post]
Boosting Endogenous Resistance of Brain to Ischemia
0 | Jan 20 2019
Sun F et al. indicated the therapeutic activation of α7 nAChRs after cerebral ischemia may serve as an important physiological responsibility of these ubiquitous receptors and holds a significant translational potential. [Read the Full Post]
Effect of VX-770 in persons with cystic fibrosis and the G551D-CFTR mutation
339 | Jan 18 2019
Accurso FJ et al. evaluated the safety and adverse-event profile of VX-770 showed that VX-770 was associated with within-subject improvements in CFTR and lung function. These findings provide support for further studies of pharmacologic potentiation of CFTR as a means to treat cystic fibrosis. [Read the Full Post]
Tezacaftor-Ivacaftor in Residual-Function Heterozygotes with Cystic Fibrosis
379 | Jan 17 2019
Rowe SM et al. showed that CFTR modulator therapy with tezacaftor-ivacaftor or ivacaftor alone was efficacious in patients with cystic fibrosis who were heterozygous for the Phe508del deletion and a CFTR residual-function mutation. [Read the Full Post]
Glucose Metabolism and AMPK Signaling Regulate Dopaminergic Cell Death Induced by Gene (α-Synuclein)-Environment (Paraquat) Interactions
325 | Jan 16 2019
Anandhan A et al. demonstrated that glucose metabolism and AMPK regulate dopaminergic cell death induced by gene (α-synuclein)-environment (PQ) interactions. [Read the Full Post]
CFTR protects against vascular inflammation and atherogenesis in apolipoprotein E-deficient mice
318 | Jan 08 2019
Li Z et al. suggested that CFTR may present a potential therapeutic target for the treatment of vascular inflammation and development of atherosclerotic disease. [Read the Full Post]
Procaine Attenuates Pain Behaviors of Neuropathic Pain Model Rats Possibly via Inhibiting JAK2/STAT3
0 | Dec 28 2018
Li D et al. indicated that procaine is capable of attenuating NPP, suggesting procaine is a potential therapeutic strategy for treating NPP. Its role may be associated with the inhibition on JAK2/STAT3 signaling. [Read the Full Post]
Spinal Glutamate Transporters Are Involved in the Development of Electroacupuncture Tolerance
525 | Dec 16 2018
Cui L et al. indicated the participation of the spinal GTs in EAT. [Read the Full Post]
Transcriptomic profiling of a chicken lung epithelial cell line (CLEC213) reveals a mitochondrial respiratory chain activity boost during influenza virus infection
320 | Dec 10 2018
Meyer L et al. suggested that AIV is able to boost the metabolic capacities of its avian host in order to provide the important energy needs required to produce progeny virus. [Read the Full Post]
Cellular uptake pathways of sepiolite nanofibers and DNA transfection improvement
373 | Nov 27 2018
Castro-Smirnov FA et al. showed that sepiolite can be spontaneously internalized into mammalian cells through both non-endocytic and endocytic pathways, macropinocytosis being one of the main pathways. Interestingly, exposure of the cells to endocytosis inhibitors, such as chloroquine, two-fold increase the efficiency of sepiolite-mediated gene transfer, in addition to the 100-fold increased resulting from sepiolite sonomechanical treatment. As sepiolite is able to bind various biological molecules, this nanoparticulate silicate could be a good candidate as a nanocarrier for simultaneous vectorization of diverse biological molecules. [Read the Full Post]
Autophagy Plays an Important Role in Anti-inflammatory Mechanisms Stimulated by Alpha7 Nicotinic Acetylcholine Receptor
404 | Nov 23 2018
Shao BZ et al. demonstrated for the first time that activating α7nAChR enhances monocyte/microglia autophagy, which suppresses neuroinflammation and thus plays an alleviative role in EAE. [Read the Full Post]
Drug-protein hydrogen bonds govern the inhibition of the ATP hydrolysis of the multidrug transporter P-glycoprotein
0 | Nov 20 2018
Chufan EE et al. revealed that screening chemical compounds for their ability to inhibit the basal ATP hydrolysis can be a reliable tool to identify modulators with high affinity for P-gp. [Read the Full Post]
Myosin-IIA regulates leukemia engraftment and brain infiltration in a mouse model of acute lymphoblastic leukemia
321 | Nov 14 2018
Wigton EJ et al. implicated myosin-IIA as a key mediator of leukemia cell migration, making it a promising target to inhibit leukemia dissemination in vivo and potentially reduce leukemia relapses. [Read the Full Post]
High-expressing cystic fibrosis transmembrane conductance regulator interacts with histone deacetylase 2 to promote the development of Ph+ leukemia through the HDAC2-mediated PTEN pathway
0 | Oct 04 2018
Yan T et al. provides strong evidence that high-expression CFTR plays an important role in the development of Ph+ leukemia through the HDAC2-mediated PTEN pathway. [Read the Full Post]
SGLT inhibitors attenuate NO-dependent vascular relaxation in the pulmonary artery but not in the coronary artery
450 | Sep 23 2018
Han Y et al. suggested that SGLT inhibitors differentially regulate vascular relaxation depending on the type of arteries, duration of the treatment, and health condition, such as diabetes. [Read the Full Post]
Inhibiting PLK1 induces autophagy of acute myeloid leukemia cells via mammalian target of rapamycin pathway dephosphorylation
0 | Sep 17 2018
Tao YF et al. may provided new insights into the molecular mechanism of PLK1 in regulating autophagy. [Read the Full Post]
Boosting Endogenous Resistance of Brain to Ischemia
490 | Sep 14 2018
Sun F et al. found that the therapeutic activation of α7 nAChRs after cerebral ischemia may serve as an important physiological responsibility of these ubiquitous receptors and holds a significant translational potential. [Read the Full Post]
Dihydromyricetin promotes autophagy and apoptosis through ROS-STAT3 signaling in head and neck squamous cell carcinoma
920 | 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]
Disruption of clathrin-dependent trafficking results in the failure of grass carp reovirus cellular entry
885 | Sep 08 2018
Wang H et al. suggested that GCRV might enter CIK cells via clathrin-mediated endocytosis in a pH-dependent manner. Additionally, dynamin is critical for efficient viral entry. [Read the Full Post]
PCSK9-deficiency does not alter blood pressure and sodium balance in mouse models of hypertension
559 | Sep 06 2018
Berger JM et al. found that PCSK9-deficiency did not alter both basal blood pressure and its increase in salt-insensitive (l-NAME) and salt-sensitive (Ang-II and DOCA-salt) hypertension models. [Read the Full Post]
Cyclopiazonic acid, an inhibitor of calcium-dependent ATPases with antiviral activity against human respiratory syncytial virus
0 | Sep 06 2018
Cui R et al. provide a new strategy for anti-RSV therapy via increasing intracellular calcium concentration. [Read the Full Post]
The Nonmetabolized β-Blocker Nadolol Is a Substrate of OCT1, OCT2, MATE1, MATE2-K, and P-Glycoprotein, but Not of OATP1B1 and OATP1B3
1735 | Sep 05 2018
Misaka S et al. indicated that these data will aid future in vivo studies on potential transporter-mediated drug-drug or drug-food interactions with involvement of nadolol. [Read the Full Post]
The diabetes medication Canagliflozin reduces cancer cell proliferation by inhibiting mitochondrial complex-I supported respiration
516 | Aug 26 2018
Villani LA et al. indicated that like the biguanide metformin, Canagliflozin not only lowers blood glucose but also inhibits complex-I supported respiration and cellular proliferation in prostate and lung cancer cells. These observations support the initiation of studies evaluating the clinical efficacy of Canagliflozin on limiting tumorigenesis in pre-clinical animal models as well epidemiological studies on cancer incidence relative to other glucose lowering therapies in clinical populations. [Read the Full Post]
Structure-dependent complexation of Fe3+ by anthracyclines. 2. The roles of methoxy and daunosamine functionalities
534 | Aug 18 2018
Nawara K et al. illustrated the important role of methoxy and daunosamine moieties in anthracycline-iron(III) complex formation and stability. [Read the Full Post]
VCP inhibitors induce endoplasmic reticulum stress, cause cell cycle arrest, trigger caspase-mediated cell death and synergistically kill ovarian cancer cells in combination with Salubrinal
442 | Aug 12 2018
Bastola P et al. provided a proof-of-concept that VCP inhibitors can be used as a single agent and can be synergized with compounds that enhance CHOP expression to induce cell death in ovarian cancer cells. [Read the Full Post]
Acute hyperglycemia suppresses left ventricular diastolic function and inhibits autophagic flux in mice under prohypertrophic stimulation
584 | Jul 28 2018
Xie J et al. found that acute hyperglycemia suppresses diastolic function, damages mitochondrial energy signaling, and inhibits autophagic flux in prohypertrophic factor-stimulated cardiomyocytes. [Read the Full Post]
Hypoxia potentiates the cytotoxic effect of piperlongumine in pheochromocytoma models
889 | 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]
Drug-protein hydrogen bonds govern the inhibition of the ATP hydrolysis of the multidrug transporter P-glycoprotein
796 | Jul 06 2018
Chufan EE et al. reveal that screening chemical compounds for their ability to inhibit the basal ATP hydrolysis can be a reliable tool to identify modulators with high affinity for P-gp. [Read the Full Post]
Loss of ARID1A expression leads to sensitivity to ROS-inducing agent elesclomol in gynecologic cancer cells
873 | 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]
Gp130-mediated STAT3 activation by S-propargyl-cysteine, an endogenous hydrogen sulfide initiator, prevents doxorubicin-induced cardiotoxicity
887 | May 11 2018
Wu J et al. offered a novel molecular basis and therapeutic strategy of H2S donor for the treatment of heart failure. [Read the Full Post]
A Platelet/CMC coupled with offline UPLC-QTOF-MS/MS for screening antiplatelet activity components from aqueous extract of Danshen
658 | Apr 30 2018
Chen Y et al. suggested their retention time was closely related to the antiplatelet aggregation activities. This study provides a rapid, effective and novel method for screening the potential antiplatelet activity components from Chinese herb medicines. [Read the Full Post]
Difference in the Pharmacokinetics and Hepatic Metabolism of Antidiabetic Drugs in Zucker Diabetic Fatty and Sprague-Dawley Rats.
608 | Feb 10 2018
Zhou X, et al. revealed that the activity for CYP3A and UGT was decreased in ZDF rats using the probe substrates, and decreased unbound intrinsic clearance in vitro for glibenclamide, canagliflozin, and troglitazone was consistent with lower plasma clearance in vivo. [Read the Full Post]
Epigenetic Regulation of Interleukin 6 by Histone Acetylation in Macrophages and Its Role in Paraquat-Induced Pulmonary Fibrosis
2266 | Feb 06 2018
Hu L et al. indicated IL-6 functioning through EMT in PQ-induced pulmonary fibrosis was regulated dynamically by HDAC and HAT both in vitro and in vivo via epigenetically regulating chromatin accessibility. [Read the Full Post]
Oxidized Low-Density Lipoprotein-Induced Cyclophilin A Secretion Requires ROCK-Dependent Diphosphorylation of Myosin Light Chain
672 | Feb 01 2018
Su Z et al. indicated that ox-LDL-induced CyPA secretion requires vesicle transportation, actin remodeling and ROCK-dependent diphosphorylation of MLC. VSMC-derived CyPA induced by ox-LDL may be associated with increased CyPA expression in atherosclerotic lesions. [Read the Full Post]
Prospective identification of resistance mechanisms to HSP90 inhibition in KRAS mutant cancer cells
1129 | Jan 20 2018
Rouhi A et al. identified potential mechanisms of acquired resistance to small molecules targeting HSP90 that may warrant proactive screening for additional HSP90 inhibitors or rational combination therapies. [Read the Full Post]
High Glucose Causes Human Cardiac Progenitor Cell Dysfunction by Promoting Mitochondrial Fission: Role of a GLUT1 Blocker
663 | Dec 28 2017
Choi HY et al. demonstrated that high glucose leads to cardiac progenitor cell dysfunction through an increase in mitochondrial fission [Read the Full Post]
Weak binding to E3 ubiquitin ligase c-Cbl increases EGFRvA protein stability
798 | Dec 04 2017
Song F et al. found that EGFRvA is more stable than EGFR because of its decreased binding to c-Cbl. [Read the Full Post]
Tissue-specific variation in nonsense mutant transcript level and drug-induced read-through efficiency in the Cln1(R151X) mouse model of INC
753 | Nov 22 2017
Thada V et al. identified a new challenge/hurdle for read-through drug therapy: variable efficiency of read-through therapy in the different tissues/organs because of tissue-specific variations in nonsense mutant transcript levels. [Read the Full Post]
Impairment of Cargo Transportation Caused by gbf1 Mutation Disrupts Vascular Integrity and Causes Hemorrhage in Zebrafish Embryos
1156 | Oct 25 2017
Chen J et al. showed that endothelial endoplasmic reticulum stress and subsequent apoptosis induced by gbf1 deficiency may account for the vascular collapse and hemorrhage. [Read the Full Post]
Nuclear Export of Ubiquitinated Proteins Determines the Sensitivity of Colorectal Cancer to Proteasome Inhibitor
704 | Oct 20 2017
Wu T et al. indicated that nuclear p53 is a major mediator in the synergistic antitumor effect of bortezomib and KPT330, and provides a rationale for the use of proteasome inhibitor together with nuclear export blocker in the treatment of colorectal cancer. It is conceivable that targeting nuclear exportation may serve as a novel strategy to overcome resistance and raise chemotherapeutic efficacy, especially for the drugs that activate the p53 system. [Read the Full Post]
Improved fluorescence assays to measure the defects associated with F508del-CFTR allow identification of new active compounds
0 | Oct 15 2017
Langron E et al. showed that most known potentiators have a negative influence on F508del-CFTR biogenesis/stability, which means membrane exposure needs to be monitored early during the development of drugs targeting CFTR. The combined use of the two fluorescence assays described here provides a useful tool for the identification of improved potentiators and correctors. The assays could also prove useful for basic scientific investigations on F508del-CFTR, and other CF-causing mutations. [Read the Full Post]
Mechanistic Approaches to Improve Correction of the Most Common Disease-Causing Mutation in Cystic Fibrosis
790 | Oct 14 2017
Bali V et al. emphasized that stabilization of ΔF508 CFTR band B in the ER might improve its functional rescue by Orkambi. [Read the Full Post]
Tetrandrine has anti-adipogenic effect on 3T3-L1 preadipocytes through the reduced expression and/or phosphorylation levels of C/EBP-α, PPAR-γ, FAS, perilipin A, and STAT-3
830 | Oct 07 2017
Jang BC et al. show that tetrandrine has strong anti-adipogenic effect on 3T3-L1 preadipocytes and the effect is largely attributable to the reduced expression and/or phosphorylation levels of C/EBP-α, PPAR-γ, FAS, perilipin A, and STAT-3. [Read the Full Post]
Improved fluorescence assays to measure the defects associated with F508del-CFTR allow identification of new active compounds
972 | Oct 04 2017
Langron E et al. showed that most known potentiators have a negative influence on F508del-CFTR biogenesis/stability, which means membrane exposure needs to be monitored early during the development of drugs targeting CFTR. The combined use of the two fluorescence assays described here provides a useful tool for the identification of improved potentiators and correctors. The assays could also prove useful for basic scientific investigations on F508del-CFTR, and other CF-causing mutations. [Read the Full Post]
Procaine Attenuates Pain Behaviors of Neuropathic Pain Model Rats Possibly via Inhibiting JAK2/STAT3
1611 | Sep 21 2017
Li D et al. indicated that procaine is capable of attenuating NPP, suggesting procaine is a potential therapeutic strategy for treating NPP. Its role may be associated with the inhibition on JAK2/STAT3 signaling. [Read the Full Post]
P-glycoprotein confers acquired resistance to 17-DMAG in lung cancers with an ALK rearrangement
734 | Sep 20 2017
Kim HJ et al. observed that the growth-inhibitory effect of 17-DMAG was decreased in A549/PR and H460/PR cells generated to over-express P-gp by long-term exposure to paclitaxel, and these cells recovered their sensitivity to 17-DMAG through the inhibition of P-gp. [Read the Full Post]
miR-203 inhibits arecoline-induced epithelial-mesenchymal transition by regulating secreted frizzled-related protein 4 and transmembrane-4 L six family member 1 in oral submucous fibrosis
924 | Sep 12 2017
Zheng L et al. provideD evidence to illustrate that miR-203 plays a role in the pathogenesis of OSF, which may be a target for OSF management. [Read the Full Post]
Riluzole partially rescues age-associated, but not LPS-induced, loss of glutamate transporters and spatial memory
1344 | Sep 11 2017
Brothers HM et al. showed that highlight the therapeutic potential of reducing glutamatergic function upon memory impairment in neurodegenerative diseases associated with aging. [Read the Full Post]
Glucose Metabolism and AMPK Signaling Regulate Dopaminergic Cell Death Induced by Gene (α-Synuclein)-Environment (Paraquat) Interactions
1033 | Jun 30 2017
Anandhan A et al. demonstrated that glucose metabolism and AMPK regulate dopaminergic cell death induced by gene (α-synuclein)-environment (PQ) interactions. [Read the Full Post]
Jatrophane Diterpenoids as Modulators of P-Glycoprotein-Dependent Multidrug Resistance (MDR): Advances of Structure-Activity Relationships and Discovery of Promising MDR Reversal Agents
0 | Jun 24 2017
Zhu J et al. showed that modifications beyond just increasing the lipophilicity of this class of Pgp inhibitors are beneficial to the activity. [Read the Full Post]
Mechanical stimulation orchestrates the osteogenic differentiation of human bone marrow stromal cells by regulating HDAC1
0 | Jun 01 2017
Wang J et al. found that mechanical stimulation orchestrates genes expression involved in the osteogenic differentiation of BMSCs via the direct regulation of HDAC1, and the therapeutic inhibition of HDAC1 may be an efficient strategy for enhancing bone formation under mechanical stimulation. [Read the Full Post]
Seminal plasma induces inflammation in the uterus through the γδ T/IL-17 pathway
3328 | May 15 2017
Song ZH et al. found a new mechanism by which seminal plasma could influence the inflammation in the uterus through the γδ T/IL-17 pathway to regulate the expression of various chemokines and cytokines. [Read the Full Post]
Resveratrol protects CA1 neurons against focal cerebral ischemic reperfusion-induced damage via the ERK-CREB signaling pathway in rats
0 | Apr 10 2017
Li Z et al found that the NMDA receptor-mediated ERK-CREB signaling pathway might participates in Res-induced neuroprotection in rats with focal cerebral ischemia. [Read the Full Post]
Beneficial metabolic actions of a stable GIP agonist following pretreatment with a SGLT2 inhibitor in high fat fed diabetic mice
1183 | Mar 26 2017
Millar PJ et al demonstratd that (DAla(2))GIP can exert beneficial metabolic control in high fat fed diabetic mice pre-treated with DAPA. The results highlight possibility of a targeted and personalized approach using a GIP agonist and SGLT2 inhibitor for the treatment of type 2 diabetes. [Read the Full Post]
Inhibition of Human UDP-Glucuronosyltransferase Enzymes by Canagliflozin and Dapagliflozin: Implications for Drug-Drug Interactions
3 | Mar 26 2017
Pattanawongsa A et al found that since the sodium-glucose cotransporter 2 inhibitors share common structural features, notably a glycoside moiety, investigation of drugs in this class for effects on UGT to identify (or exclude) potential drug-drug interactions is warranted. [Read the Full Post]
Structural and functional screening in human induced-pluripotent stem cell-derived cardiomyocytes accurately identifies cardiotoxicity of multiple drug types
0 | Mar 17 2017
Doherty KR et al. showed that a multi-parameter approach examining both cardiac cell health and function in hiPS-CM provides a comprehensive and robust assessment that can aid in the determination of potential cardiac liability. [Read the Full Post]
Structural and functional screening in human induced-pluripotent stem cell-derived cardiomyocytes accurately identifies cardiotoxicity of multiple drug types
1504 | Mar 16 2017
Doherty KR et al. found that a multi-parameter approach examining both cardiac cell health and function in hiPS-CM provides a comprehensive and robust assessment that can aid in the determination of potential cardiac liability. [Read the Full Post]
Inhibition of Human UDP-Glucuronosyltransferase Enzymes by Canagliflozin and Dapagliflozin: Implications for Drug-Drug Interactions
1414 | Jan 29 2017
Pattanawongsa A et al. reported the inhibition of human recombinant UGTs by CNF and DPF, along with the Ki values for selected recombinant and human liver microsomal UGTs. [Read the Full Post]
Jatrophane Diterpenoids as Modulators of P-Glycoprotein-Dependent Multidrug Resistance (MDR): Advances of Structure-Activity Relationships and Discovery of Promising MDR Reversal Agents
2172 | Dec 28 2016
Zhu J, et al found that compound 26, which exhibited a remarkable metabolic stability in vitro and a favorable antitumor effect in vivo, would serve as a promising lead for the development of new MDR reversal agents. [Read the Full Post]
Tetrandrine has anti-adipogenic effect on 3T3-L1 preadipocytes through the reduced expression and/or phosphorylation levels of C/EBP-α, PPAR-γ, FAS, perilipin A, and STAT-3
1339 | Nov 22 2016
Jang BC et al. showed that tetrandrine has strong anti-adipogenic effect on 3T3-L1 preadipocytes and the effect is largely attributable to the reduced expression and/or phosphorylation levels of C/EBP-α, PPAR-γ, FAS, perilipin A, and STAT-3. [Read the Full Post]
Mechanistic Approaches to Improve Correction of the Most Common Disease-Causing Mutation in Cystic Fibrosis
1256 | Nov 14 2016
Bali V et al. found that stabilization of ΔF508 CFTR band B in the ER might improve its functional rescue by Orkambi. [Read the Full Post]
Levetiracetam mitigates doxorubicin-induced DNA and synaptic damage in neurons
2058 | Oct 27 2016
Manchon JF et al. found that levetiracetam might be part of a valuable new approach for mitigating synaptic damage and, perhaps, for treating cognitive disturbances in cancer patients and survivors. [Read the Full Post]
Mechanical stimulation orchestrates the osteogenic differentiation of human bone marrow stromal cells by regulating HDAC1
4905 | Oct 27 2016
Wang J et al. found that mechanical stimulation orchestrates genes expression involved in the osteogenic differentiation of BMSCs via the direct regulation of HDAC1, and the therapeutic inhibition of HDAC1 may be an efficient strategy for enhancing bone formation under mechanical stimulation. [Read the Full Post]
Seminal plasma induces inflammation in the uterus through the γδ T/IL-17 pathway
1721 | Oct 13 2016
Song ZH et al. found a new mechanism by which seminal plasma could influence the inflammation in the uterus through the γδ T/IL-17 pathway to regulate the expression of various chemokines and cytokines. [Read the Full Post]
Resveratrol protects CA1 neurons against focal cerebral ischemic reperfusion-induced damage via the ERK-CREB signaling pathway in rats
1571 | Sep 13 2016
Li Z, et al. showed that the NMDA receptor-mediated ERK-CREB signaling pathway might participates in Res-induced neuroprotection in rats with focal cerebral ischemia. [Read the Full Post]
Beneficial metabolic actions of a stable GIP agonist following pre-treatment with a SGLT2 inhibitor in high fat fed diabetic mice
1508 | Sep 05 2016
Millar PJ, et al. demonstrated possibility of a targeted and personalized approach using a GIP agonist and SGLT2 inhibitor for the treatment of type 2 diabetes. [Read the Full Post]
Two strategies to overcome eribulin resistance: pharmacokinetic imaging and nanoparticle delivery system
4981 | Nov 17 2014
Laughney et al. developed strategies of pharmacokinetic for to reveal drug-resistant mechanisms, and nanoparticle system to overcome the resistance. [Read the Full Post]
A new neurogenic receptor activator of P2Y1——Up4A
4220 | Nov 13 2014
Recently, researchers from Nevada School of Medicine found a novel factor, Up4A, may contribute in mediating enteric inhibitory neurotransmission of the intestines, acts through P2Y1 receptors and apamin-sensitive small-conductance SK channels. [Read the Full Post]
Tariquidar is a P glycoprotein inhibitor undergoing research
4044 | Jan 27 2014
Tariquidar (XR9576) is a potent and selective noncompetitive inhibitor of P-glycoprotein with Kd of 5.1 nM, reverses drug resistance in MDR cell Lines. [Read the Full Post]
Tariquidar is a P glycoprotein inhibitor undergoing research
4065 | Dec 30 2013
Tariquidar displays high-affinity binding to P-gp with Bmax of 275 pmol/mg. [Read the Full Post]
Zosuquidar is a compound of antineoplastic drug
3856 | Dec 30 2013
Zosuquidar (LY335979) is a potent modulator of P-glycoprotein-mediated multi-drug resistance with Ki of 60 nM. [Read the Full Post]
Brefeldin A used to enhance intracellular cytokine staining signals
2804 | Dec 23 2013
Brefeldin A is a lactone antibiotic and ATPase inhibitor for protein transport with IC50 of 0.2 μM in HCT 116 cells, induces cancer cell differentiation and apoptosis. [Read the Full Post]
Dapagliflozin is a drug used to treat type 2 diabetes
0 | Dec 20 2013
Dapagliflozin is 32-fold more potent than phlorizin against hSGLT2 but 4-fold less than phlorizin against hSGLT1. [Read the Full Post]
LY335979 is a potent inhibitor that contains a cyclopropyldibenzosuberane moiety
4089 | Dec 16 2013
LY335979 competitively inhibits equilibrium binding of vinblastine to Pgp by blocking azidopine photoaffinity labeling of the Pgp in CEM/VLB100 plasma membranes. [Read the Full Post]
VX 770 is a drug approved for patients with a certain mutation of cystic fibrosis
2469 | Dec 09 2013
Ivacaftor (VX-770, Kalydeco) is a potentiator of CFTR targeting G551D-CFTR and F508del-CFTR with EC50 of 100 nM and 25 nM, respectively. [Read the Full Post]
Dapagliflozin is a drug used to treat type 2 diabetes
2526 | Nov 27 2013
Dapagliflozin is not sensitive to hSGLT1 with a 1200-fold IC50. [Read the Full Post]
VX809 is an experimental drug for the treatment of cystic fibrosis
2676 | Oct 28 2013
VX-809 acts at the level of the ER to allow a fraction of the F508del-CFTR to adopt a properly folded form, to exit the ER and mobilize to the cell surface for normal functioning. [Read the Full Post]
Tariquidar is a P glycoprotein inhibitor undergoing research as an adjuvant
3705 | Oct 23 2013
Tariquidar is a potent and selective noncompetitive inhibitor of P-glycoprotein with Kd of 5.1 nM, reverses drug resistance in MDR cell Lines. [Read the Full Post]
MRS2578 is a selective antagonist of P2Y6 nucleotide receptors
2591 | Jul 29 2013
MRS 2578 (10 μM) significant reduces TNF-α–induced proinflammatory gene expression in HMEC-1 cells. [Read the Full Post]
Ouabain isolated from plants is widely used by scientists in in vitro studies
2971 | May 30 2013
In many non rodent species, low concentrations of this substance (i.e., in the subnanomolar range) may stimulate the Na-K-ATPase. The mechanism of the stimulatory effect is not understood and remains controversial. Further, the issue in rodents is more complicated because there are different isoforms of the Na-K-ATPase - some of which are very sensitive to ouabain while others are not. [Read the Full Post]
Ouabain is found in the ripe seeds of African plants
3144 | May 14 2013
It is well understood that the classical mechanism of action of ouabain involves its binding to and inhibition of the plasma membrane Na+/K+-ATPase (sodium pump) especially at the higher concentrations attainable in vitro or with intravenous dosage. [Read the Full Post]
Tolbutamide is a type of medicine called a sulphonylurea
2882 | Feb 17 2013
Surgery was performed using aseptic procedures. Anaesthesia was induced using ketamine, which was followed by 2 C5% isofluorane Tolbutamide mixed with oxygen administered by inhalation for the length of the surgical procedure. The skin and fascia were removed from the dorsal surface of the skull. [Read the Full Post]
Tolbutamide is a first generation potassium channel blocker
2823 | Feb 01 2013
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by excessive and chronic activation of inflammatory pathways via immune Tolbutamide complex deposition, complement activation, and Fc receptor (FcR) ligation, often leading to significant clinical pathologies including glomerulonephritis [Read the Full Post]
Oligomycin A CGMP or cAMP in the lysates were by radioimmunoassay
3811 | Oct 23 2012
CGMP or cAMP in the lysates were by radioimmunoassay of cGMP from Amersham or with protein kinase type I muscle beef, each determined. Activity t and PIP3 [Read the Full Post]
