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GPCR & G Protein

Pharmacokinetics and Biodistribution of GDC-0449 Loaded Micelles in Normal and Liver Fibrotic Mice

18 | Sep 26 2019

Dutta R et al. showed that M6P-conjugated GDC-0449 loaded mixed micelles may be used as a potential drug delivery vehicle for treating liver fibrosis. [Read the Full Post]

Cellular Cholesterol Directly Activates Smoothened in Hedgehog Signaling

18 | Sep 23 2019

Huang P et al. proposed that the endogenous Smoothened activator is cholesterol, not oxysterols, and that vertebrate Hedgehog signaling controls Smoothened by regulating its access to cholesterol. [Read the Full Post]

Vorapaxar: The Current Role and Future Directions of a Novel Protease-Activated Receptor Antagonist for Risk Reduction in Atherosclerotic Disease

45 | Jul 09 2019

Gryka RJ et al. indicated vorapaxar provides clinicians with a novel mechanism of action to further reduce the burden of ischemic heart disease. Identification of patients with a high ischemic risk and low bleeding risk would enable clinicians to maximize the utility of this unique agent. [Read the Full Post]

Efficacy of Ramelteon for delirium after lung cancer surgery

61 | Jun 20 2019

Miyata R et al. showed that Ramelteon is likely to reduce the incidence and intensity of delirium after surgery for lung cancer in elderly patients. [Read the Full Post]

Effect of bucladesine, pentoxifylline, and H-89 as cyclic adenosine monophosphate analog, phosphodiesterase, and protein kinase A inhibitor on acute pain

53 | Jun 09 2019

Salehi F et al. indicated PTX, H-89, and Db-cAMP affect the thermal-induced pain by probably interacting with intracellular cAMP and cGMP signaling pathways and cyclic nucleotide-dependent protein kinases. [Read the Full Post]

Combining Smoothened Agonist and NEL-Like Protein-1 Enhances Bone Healing

147 | Apr 12 2019

Lee S et al. suggested that combining the hedgehog signaling agonist SAG and NELL-1 has potential as a novel therapeutic strategy for the healing of critical-size bone defects. Future directions will include optimization of dosage and delivery strategy for an SAG and NELL-1 combination product. [Read the Full Post]

Ultraviolet A eye irradiation ameliorates colon carcinoma induced by azoxymethane and dextran sodium sulfate through β-endorphin and methionine-enkephalin

0 | Mar 16 2019

Hiramoto K et al. suggested that UVA eye irradiation exerts major effects on AOM + DSS-induced colon carcinoma. [Read the Full Post]

The microRNA-7-mediated reduction in EPAC-1 contributes to vascular endothelial permeability and eNOS uncoupling in murine experimental retinopathy

79 | Mar 16 2019

Garcia-Morales V et al. indicated that EPAC-1 resembles an efficacious and druggable target molecule for the amelioration of (diabetic) retinopathy. [Read the Full Post]

Cyclopamine: from cyclops lambs to cancer treatment

113 | Mar 01 2019

Lee ST et al. showed inhibitors of the Hh signaling pathway, including cyclopamine derivatives, have been targeted as potential treatments for certain cancers and other diseases associated with the Hh signaling pathway. [Read the Full Post]

Antiangiogenic Effects of Doxazosin on Experimental Choroidal Neovascularization in Mice

99 | Feb 28 2019

Guo J et al. found that Doxazosin exerts antiangiogenic actions in an experimental mouse model of CNV and may be a potential adjunctive therapy for neovascular age-related macular degeneration in humans. [Read the Full Post]

Nano-emulsions as vehicles for topical delivery of forskolin

113 | Feb 14 2019

Miastkowska M et al. showed that the nano-emulsions developed in this study could be used as effective carriers for topical administration of forskolin. [Read the Full Post]

Comparison of cell-based assays for the identification and evaluation of competitive CXCR4 inhibitors

243 | Feb 07 2019

CXCL12 competition binding studies were proven to be highly valuable as an initial screening assay and indicative for the pharmacological and functional profile of competitive CXCR4 antagonists, which will help the design of new potent CXCR4 inhibitors. [Read the Full Post]

Disruption of SHH signaling cascade by SBE attenuates lung cancer progression and sensitizes DDP treatment

0 | Jan 27 2019

Du J et al. suggested SBE as a novel drug candidate for NSCLC which specifically and sensitively targets SHH signaling pathway. [Read the Full Post]

Ultraviolet A eye irradiation ameliorates colon carcinoma induced by azoxymethane and dextran sodium sulfate through β-endorphin and methionine-enkephalin

248 | Jan 25 2019

Hiramoto K et al. suggested that UVA eye irradiation exerts major effects on AOM + DSS-induced colon carcinoma. [Read the Full Post]

Glucose Metabolism and AMPK Signaling Regulate Dopaminergic Cell Death Induced by Gene (α-Synuclein)-Environment (Paraquat) Interactions

117 | 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]

PAFR selectively mediates radioresistance and irradiation-induced autophagy suppression in prostate cancer cells

141 | Jan 07 2019

Yao B et al. elucidated a significant role of GB in selectively improving the outcomes of PCa receiving radiation therapy. [Read the Full Post]

IL27 controls skin tumorigenesis via accumulation of ETAR-positive CD11b cells in the pre-malignant skin

110 | Dec 31 2018

Dibra D et al. indicated that these findings are clinically relevant, as the number of IL27RA-positive cells in the stroma is highly related to tumor de-differentiation in patients with squamous cell carcinomas. [Read the Full Post]

Tracking gastrointestinal transit of solids in aged rats as pharmacological models of chronic dysmotility

0 | Dec 28 2018

Dalziel JE et al. demonstrated that loperamide slowed overall transit in aged rats, while prucalopride increased stomach emptying and accelerates colonic transit. [Read the Full Post]

5-HT4 receptors facilitate cholinergic neurotransmission throughout the murine gastrointestinal tract

322 | Dec 11 2018

Pauwelyn V et al. showed that in the murine gastrointestinal tract, activation of 5-HT4 receptors with prucalopride enhances cholinergic contractions, illustrating facilitation of myenteric cholinergic neurotransmission. The degree of enhancement with prucalopride is of similar magnitude as previously reported in other species, but the effective concentrations are lower than those needed in the gastrointestinal tract of other species. [Read the Full Post]

Anti-invasive effects of CXCR4 and FAK inhibitors in non-small cell lung carcinomas with mutually inactivated p53 and PTEN tumor suppressors

355 | Dec 07 2018

Dragoj M et al. demonstrated that p53/PTEN deficient NSCLCs have extremely invasive phenotype and provided a rationale for the use of CXCR4 or FAK inhibitors for the suppression of NSCLC dissemination. [Read the Full Post]

Disruption of SHH signaling cascade by SBE attenuates lung cancer progression and sensitizes DDP treatment

268 | Nov 30 2018

Du J et al. suggested SBE as a novel drug candidate for NSCLC which specifically and sensitively targets SHH signaling pathway. [Read the Full Post]

Levo-Tetrahydroberberrubine Produces Anxiolytic-Like Effects in Mice through the 5-HT1A Receptor

245 | Nov 30 2018

Mi G et al. suggested that l-THBr may produce potent anxiolytic-like effects mainly through serotonin receptors. [Read the Full Post]

Acquired resistance to combination treatment through loss of synergy with MEK and PI3K inhibitors in colorectal cancer

0 | Oct 14 2018

Bhattacharya B et al. highlight that AQR to combination treatment may develop through alternative mechanisms to those of single agent treatment, including a change in drug interaction. [Read the Full Post]

Experimental observation of human bone marrow mesenchymal stem cell transplantation into rabbit intervertebral discs

363 | Sep 30 2018

Tao H et al. indicated that in the sections of specimens removed at 1, 2, 4, 6 and 8 weeks post-transplantation, no GFP-positive cells were observed in the control groups, whereas GFP-positive cells were apparent in the nucleus pulposus at all periods in the GFP-labeled human BMSCs group, and the cell density at 6 and 8 weeks was significantly less than that at 1, 2 and 4 weeks post-transplantation (P<0.001). [Read the Full Post]

SGLT inhibitors attenuate NO-dependent vascular relaxation in the pulmonary artery but not in the coronary artery

272 | 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]

The Effects of Ultraviolet Eye Irradiation on Dextran Sodium Sulfate-Induced Ulcerative Colitis in Mice

539 | Sep 15 2018

Hiramoto K et al. suggested that UV eye irradiation plays an important role in DSS-induced ulcerative colitis. [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

311 | Sep 14 2018

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]

Disruption of clathrin-dependent trafficking results in the failure of grass carp reovirus cellular entry

527 | 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]

Upregulation of programmed cell death ligand 1 promotes resistance response in non-small-cell lung cancer patients treated with neo-adjuvant chemotherapy

1243 | Aug 26 2018

Zhang P et al. suggested that the upregulation of PD-L1 promotes a resistance response in lung cancer cells that might be through activation of the phosphatidylinositol 3-kinase/protein kinase B pathway and suppression of tumor-infiltrating lymphocytes. The high expression of PD-L1 after NAC could be an indication of therapeutic resistance and poor prognosis in patients with non-small-cell lung cancer. [Read the Full Post]

The diabetes medication Canagliflozin reduces cancer cell proliferation by inhibiting mitochondrial complex-I supported respiration

316 | 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]

CRISPR/Cas-Mediated Knockin in Human Pluripotent Stem Cells

502 | Aug 17 2018

The transfection procedures described could also be used for additional applications, such as overexpression or lineage tracing studies. [Read the Full Post]

Cross-talk between Notch and Hedgehog regulates hepatic stellate cell fate in mice

537 | Jul 14 2018

Xie G, et al. found that the Notch and Hedgehog pathways interact to control the fate of key cell types involved in adult liver repair by modulating epithelial-to-mesenchymal-like/mesenchymal-to-epithelial-like transitions. [Read the Full Post]

AT13148, a first-in-class multi-AGC kinase inhibitor, potently inhibits gastric cancer cells both in vitro and in vivo

1941 | Jun 20 2018

Xi Y et al. supported the progression of this molecule into future evaluation as a valuable anti-gastric cancer candidate. [Read the Full Post]

Both genetic deletion and pharmacological blockade of lysophosphatidic acid LPA1 receptor results in increased alcohol consumption

333 | Jun 17 2018

Castilla-Ortega E et al. suggested a relevant role for the LPA/LPA1 signaling system in alcoholism. In addition, the LPA1-null mice emerge as a new model for genetic vulnerability to excessive alcohol drinking. The pharmacological manipulation of LPA1 receptor arises as a new target for the study and treatment of alcoholism. [Read the Full Post]

Lysophosphatidic acid upregulates connective tissue growth factor expression in osteoblasts through the GPCR/PKC and PKA pathways

439 | Jun 17 2018

Yu ZL et al. indicated that LPA increases CCN2 expression through the activation of PKC and PKA. Thus, the regulatory functions of the PKC and PKA pathways are implicated in the LPA-induced increase in CCN2 expression. [Read the Full Post]

Targeting colorectal cancer cells by a novel sphingosine kinase 1 inhibitor PF-543

319 | Jun 06 2018

Ju T et al. found that mitochondrial programmed necrosis pathway is likely the key mechanism responsible for PF-543's actions in CRC cells. [Read the Full Post]

Unique roles of Akt1 and Akt2 in IGF-IR mediated lung tumorigenesis

948 | May 21 2018

Franks SE et al. suggested that compounds selectively targeting AKT1 may prove more effective than compounds that inhibit all three AKT isoforms at least in the treatment of lung adenocarcinoma. [Read the Full Post]

PI3Kα isoform-dependent activation of RhoA regulates Wnt5a-induced osteosarcoma cell migration

2916 | May 20 2018

Zhang A et al. demonstrated that RhoA acts as the downstream of PI3K/Akt signaling (specific PI3Kα, Akt1 and Akt2 isoforms) and mediated Wnt5a-induced the migration of osteosarcoma cells. [Read the Full Post]

Gli1-Mediated Regulation of Sox2 Facilitates Self-Renewal of Stem-Like Cells and Confers Resistance to EGFR Inhibitors in Non-Small Cell Lung Cancer

563 | May 18 2018

Bora-Singhal N et al. demonstrated a cooperative functioning of the EGFR signaling and Hedgehog pathways in governing the stem-like functions of NSCLC cancer stem cells and presents a novel therapeutic strategy to combat NSCLC harboring EGFR mutations. [Read the Full Post]

Stimulation of Transforming Growth Factor-β1-Induced Endothelial-To-Mesenchymal Transition and Tissue Fibrosis by Endothelin-1 (ET-1): A Novel Profibrotic Effect of ET-1

334 | May 12 2018

Wermuth PJ et al. suggested a novel role for ET-1 in the establishment and progression of tissue fibrosis. [Read the Full Post]

Prenatal caffeine exposure induced a lower level of fetal blood leptin mainly via placental mechanism

488 | Apr 27 2018

Wu YM et al. found that PCE decreased fetal blood leptin mainly via reducing the expression and transportation of leptin in the placenta. [Read the Full Post]

Modulation of Nav1.8 by Lysophosphatidic Acid in the Induction of Bone Cancer Pain

381 | Apr 26 2018

Pan HL et al. demonstrated the modulation of Nav1.8 by LPA in DRG neurons, and that this probably underlies the peripheral mechanism by which bone cancer pain is induced. [Read the Full Post]

Suppression of chronic lymphocytic leukemia progression by CXCR4 inhibitor WZ811

808 | Apr 25 2018

Li SH et al. demonstrated that WZ811 may be a novel approach in the treatment of chronic lymphocytic leukemia. [Read the Full Post]

Evaluation of cardioprotective effect of aqueous extract of Garcinia indica Linn. fruit rinds on isoprenaline-induced myocardial injury in Wistar albino rats

619 | Apr 18 2018

Patel KJ et al. found that the aqueous extract of G. indica was not found to be cardioprotective against myocardial injury. [Read the Full Post]

Critical role of CXCL4 in the lung pathogenesis of influenza (H1N1) respiratory infection

888 | Apr 02 2018

Guo L et al. identified CXCL4 as a vital immunoregulatory chemokine essential for protecting mice against influenza A virus infection, especially as it affects the development of lung injury and neutrophil mobilization to the inflamed lung. [Read the Full Post]

Adiponectin promotes human jaw bone marrow mesenchymal stem cell chemotaxis via CXCL1 and CXCL8

0 | Apr 01 2018

Pu Y et al. supported the above results. Our data suggest that APN can promote h-JBMMSC chemotaxis by up-regulating CXCL1 and CXCL8. [Read the Full Post]

Mutant p53 in concert with an interleukin-27 receptor alpha deficiency causes spontaneous liver inflammation, fibrosis, and steatosis in mice

0 | Mar 21 2018

Dibra D et al. found that he combination of mutant p53 and IL27RA(-/-) causes spontaneous liver inflammation, steatosis, and fibrosis in vivo, whereas either gene alone in vivo has no effects on the liver. [Read the Full Post]

Relative cytotoxic potencies and cell death mechanisms of α1 -adrenoceptor antagonists in prostate cancer cell lines

0 | Mar 17 2018

Forbes A et al. demonstrated cytotoxic actions on both castration-resistant PC-3 and androgen-sensitive LNCap prostate cancer cells. [Read the Full Post]

Aberrant activation of hedgehog signaling promotes cell proliferation via the transcriptional activation of forkhead Box M1 in colorectal cancer cells

735 | Mar 13 2018

Wang D et al. indicated the dysregulation of the Hh-Gli1-FoxM1 axis is essential for the proliferation and growth of human CRC cells and offers a potent target for therapeutic intervention in CRC. [Read the Full Post]

Nek2A/SuFu feedback loop regulates Gli-mediated Hedgehog signaling pathway

675 | Mar 12 2018

Zhou F et al. uncovered one of the mechanisms by which Nek2A acts as a modulator of the Hh signaling pathway in the context of a novel negative-feedback loop, which may offer new insights into Gli-mediated Hh signaling regulation in development and human diseases. [Read the Full Post]

IgG subclasses determine pathways of anaphylaxis in mice

0 | Mar 09 2018

Beutier H et al. proposed that the differential expression of inhibitory FcγRIIB on myeloid cells and its differential binding of IgG subclasses controls the contributions of mast cells, basophils, neutrophils, and macrophages to IgG subclass-dependent anaphylaxis. [Read the Full Post]

PI-3K Inhibitors Preferentially Target CD15+ Cancer Stem Cell Population in SHH Driven Medulloblastoma

652 | Feb 28 2018

Singh AR, et al. suggested a sequential combination of PI-3K inhibitors and chemotherapy will have augmented efficacy in the treatment of this disease. [Read the Full Post]

Difference in the Pharmacokinetics and Hepatic Metabolism of Antidiabetic Drugs in Zucker Diabetic Fatty and Sprague-Dawley Rats.

423 | 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]

CXCL2/MIF-CXCR2 signaling promotes the recruitment of myeloid-derived suppressor cells and is correlated with prognosis in bladder cancer

1080 | Jan 25 2018

Zhang H et al. identified the CXCL2/MIF-CXCR2 axis as an important mediator in MDSC recruitment and as predictors and potential therapeutic targets in BC patients. [Read the Full Post]

mTORC2 mediates CXCL12-induced angiogenesis

1141 | Jan 07 2018

Ziegler ME et al. identified mTORC2 as a critical signaling nexus downstream of CXCL12/CXCR4 that represents a potential link between mTORC2, metabolic regulation, and angiogenesis. [Read the Full Post]

High Glucose Causes Human Cardiac Progenitor Cell Dysfunction by Promoting Mitochondrial Fission: Role of a GLUT1 Blocker

504 | 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]

Melatonin alleviates inflammasome-induced pyroptosis through inhibiting NF-κB/GSDMD signal in mice adipose tissue

879 | Dec 13 2017

Liu Z et al. revealed a novel function of melatonin on adipocyte pyroptosis, suggesting a new potential therapy for melatonin to prevent and treat obesity caused systemic inflammatory response. [Read the Full Post]

The HDAC Inhibitor LAQ824 Enhances Epigenetic Reprogramming and In Vitro Development of Porcine SCNT Embryos.

776 | Dec 13 2017

Optimum exposure (100 nM for 24 h) to LAQ824 post-activation improved the in vitro development of porcine SCNT embryos by enhancing levels of H3K9 and H4K12, reducing 5-mC, and regulating gene expression. [Read the Full Post]

Hedgehog pathway is involved in nitidine chloride induced inhibition of epithelial-mesenchymal transition and cancer stem cells-like properties in breast cancer cells

1026 | Nov 25 2017

Sun M et al. suggested that NC may be a potential anticancer agent for breast cancer. [Read the Full Post]

Sphingosine kinase inhibition ameliorates chronic hypoperfusion-induced white matter lesions

557 | Nov 10 2017

Yang Y et al. suggested a mechanism for hypoperfusion-associated WML involving HIF-1α-SphK2-S1P-mediated disruption of OPC differentiation, and proposes the SphK signaling pathway as a potential therapeutic target for white matter disease. [Read the Full Post]

Cytokine correlation analysis based on drug perturbation

2160 | Oct 17 2017

Wallner FK et al. showed that cytokines are highly co-regulated, which provide valuable information for how a therapeutic drug might affect clusters of cytokines. In addition, a cytokine that is used as a therapeutic biomarker could be combined with its related cytokines into a biomarker panel to improve diagnostic accuracy. [Read the Full Post]

Cannabinoid receptor-2 stimulation suppresses neuroinflammation by regulating microglial M1/M2 polarization through the cAMP/PKA pathway in an experimental GMH rat model.

0 | Oct 06 2017

Tao Y et al. proposed that promotion of microglial M2 polarization through the cAMP/PKA pathway participates in the CB2R-mediated anti-inflammatory effects after GMH induction. [Read the Full Post]

Overexpression of cannabinoid receptor 1 promotes renal cell carcinoma progression

650 | Sep 13 2017

Wang J et al. suggested that CB1 might be a potential target for RCC clinical therapy. [Read the Full Post]

Intrathecal Intermittent Orexin-A Causes Sympathetic Long-Term Facilitation and Sensitizes the Peripheral Chemoreceptor Response to Hypoxia in Rats

1043 | Sep 12 2017

Kim SJ et al. revealed that the activation of spinal orexin receptors is critical to enhance peripheral chemoreceptor responses to hypoxia after AIH. [Read the Full Post]

Tracking gastrointestinal transit of solids in aged rats as pharmacological models of chronic dysmotility

1246 | Sep 11 2017

Dalziel JE et al. demonstrated that loperamide slowed overall transit in aged rats, while prucalopride increased stomach emptying and accelerates colonic transit. [Read the Full Post]

Niacin receptor GPR109A inhibits insulin secretion and is down-regulated in type 2 diabetic islet beta-cells

1393 | Aug 07 2017

Wang N et al. demonstrated that GPR109A is functionally expressed in both human and murine islet beta-cells. However, the role of GPR109A in the prevention of diabetes or insulinoma needs further study. [Read the Full Post]

Glucose Metabolism and AMPK Signaling Regulate Dopaminergic Cell Death Induced by Gene (α-Synuclein)-Environment (Paraquat) Interactions

854 | 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]

Structural basis of Smoothened regulation by its extracellular domains

1299 | Jun 22 2017

Byrne EF et al. clarified the structural mechanism by which the activity of a GPCR is controlled by ligand-regulated interactions between its extracellular and transmembrane domains. [Read the Full Post]

The gender differences in the inhibitory action of UVB-induced melanocyte activation by the administration of tranexamic acid

0 | Jun 04 2017

Hiramoto K et al. suggested that the suppression by tranexamic acid of the UVB-induced melanocyte activation (UVB sensitivity) is stronger in female mice than in male mice and that female hormones and β-endorphin play an important role in this sex difference. [Read the Full Post]

GLI inhibitor GANT61 kills melanoma cells and acts in synergy with obatoclax

0 | May 05 2017

Vlčková K et al. found that GANT61 treatment might become a hopeful and effective anti-melanoma targeted therapy, especially when combined with the BCL2 family inhibitor obatoclax. [Read the Full Post]

GLI inhibitor GANT61 kills melanoma cells and acts in synergy with obatoclax

1316 | Apr 27 2017

Vlčková K et al. found that GANT61 treatment might become a hopeful and effective anti-melanoma targeted therapy, especially when combined with the BCL2 family inhibitor obatoclax. [Read the Full Post]

"RNA polymerase III component Rpc9 regulates hematopoietic stem and progenitor cell maintenance in zebrafish. "

0 | Apr 17 2017

Wei Y et al illustrated that Rpc9, a component of Pol III, plays an important tissue-specific role in HSPC maintenance during zebrafish embryogenesis and might be conserved across vertebrates, including mammals. [Read the Full Post]

Signaling factors and pathways of α-particle irradiation induced bilateral bystander responses between Beas-2B and U937 cells

0 | Apr 12 2017

Fu J et al disclosed novel signaling cascades of macrophage-mediated bilateral bystander responses that the release of TNF-α and IL-8 regulated by MAPK and NF-κB pathways synergistically increased cellular injury after α-particle irradiation. [Read the Full Post]

The gender differences in the inhibitory action of UVB-induced melanocyte activation by the administration of tranexamic acid

0 | Mar 28 2017

Hiramoto K et al suggested that the suppression by tranexamic acid of the UVB-induced melanocyte activation (UVB sensitivity) is stronger in female mice than in male mice and that female hormones and β-endorphin play an important role in this sex difference. [Read the Full Post]

Beneficial metabolic actions of a stable GIP agonist following pretreatment with a SGLT2 inhibitor in high fat fed diabetic mice

987 | 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]

IgG subclasses determine pathways of anaphylaxis in mice

2077 | Feb 27 2017

Beutier H et al. proposed that the differential expression of inhibitory FcγRIIB on myeloid cells and its differential binding of IgG subclasses controls the contributions of mast cells, basophils, neutrophils, and macrophages to IgG subclass-dependent anaphylaxis. Collectively, our results unravel novel complexities in the involvement and regulation of cell populations in IgG-dependent reactions in vivo. [Read the Full Post]

Relative cytotoxic potencies and cell death mechanisms of α1 -adrenoceptor antagonists in prostate cancer cell lines

1619 | Feb 24 2017

Prazosin and doxazosin demonstrated cytotoxic actions on both castration-resistant PC-3 and androgen-sensitive LNCap prostate cancer cells. The mechanisms involved included changes in a number of proliferation and apoptosis regulatory proteins. The role of autophagy depended on the cell type, but contributed to cell death in PC3 cells. [Read the Full Post]

Mutant p53 in concert with an interleukin-27 receptor alpha deficiency causes spontaneous liver inflammation, fibrosis, and steatosis in mice

984 | Feb 22 2017

The combination of mutant p53 and IL27RA(-/-) causes spontaneous liver inflammation, steatosis, and fibrosis in vivo, whereas either gene alone in vivo has no effects on the liver. [Read the Full Post]

SMO Gene Amplification and Activation of the Hedgehog Pathway as Novel Mechanisms of Resistance to Anti-Epidermal Growth Factor Receptor Drugs in Human Lung Cancer

1416 | Feb 21 2017

Della Corte CM, et al.'s result supports the role of the Hh pathway in mediating resistance to anti-EGFR-TKIs through the induction of EMT and suggests new opportunities to design new treatment strategies in lung cancer. [Read the Full Post]

Targeting hedgehog signaling reduces self-renewal in embryonal rhabdomyosarcoma

0 | Feb 20 2017

Satheesha S, et al.‘s ’ work identifies novel functional aspects of hedgehog signaling in ERMS, redefines the rationale for its targeting as means to control ERMS self-renewal and underscores the importance of studying functional tumor heterogeneity in pediatric cancers. [Read the Full Post]

Targeting Wnt pathway in mantle cell lymphoma-initiating cells

0 | Feb 20 2017

Mathur R, et al.‘s’ results suggest that Wnt signaling is critical for the maintenance and survival of MCL-ICs, and effective MCL therapy should aim to eliminate MCL-ICs through Wnt signaling inhibitors. [Read the Full Post]

Survivin as a therapeutic target in Sonic hedgehog-driven medulloblastoma

0 | Feb 19 2017

Brun SN, et al.'s studies highlight the importance of Survivin in SHH-driven MB, and suggest that it may represent a novel therapeutic target in patients with this disease. [Read the Full Post]

Cyclopiazonic acid, an inhibitor of calcium-dependent ATPases with antiviral activity against human respiratory syncytial virus

0 | Feb 10 2017

Cui R et al.‘s’ findings provide a new strategy for anti-RSV therapy via increasing intracellular calcium concentration. [Read the Full Post]

Human UDP-glucuronosyltransferase (UGT) 2B10: Validation of cotinine as a selective probe substrate, inhibition by UGT enzyme selective inhibitors and antidepressant and antipsychotic drugs, and structural determinants of enzyme inhibition

1772 | Feb 09 2017

Pattanawongsa A, et al.'s result indicates that these drugs may perpetrate inhibitory drug-drug interactions when coadministered with compounds that are cleared predominantly by UGT2B10. [Read the Full Post]

The gender differences in the inhibitory action of UVB-induced melanocyte activation by the administration of tranexamic acid.

2224 | Feb 01 2017

Hiramoto K et al. suggested that the suppression by tranexamic acid of the UVB-induced melanocyte activation (UVB sensitivity) is stronger in female mice than in male mice and that female hormones and β-endorphin play an important role in this sex difference. [Read the Full Post]

Inhibition of Human UDP-Glucuronosyltransferase Enzymes by Canagliflozin and Dapagliflozin: Implications for Drug-Drug Interactions

1234 | 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]

SMO Gene Amplification and Activation of the Hedgehog Pathway as Novel Mechanisms of Resistance to Anti-Epidermal Growth Factor Receptor Drugs in Human Lung Cancer

1007 | Jan 11 2017

Della Corte CM et al. found that the role of the Hh pathway in mediating resistance to anti-EGFR-TKIs through the induction of EMT and suggests new opportunities to design new treatment strategies in lung cancer. [Read the Full Post]

Targeting Wnt pathway in mantle cell lymphoma-initiating cells

3586 | Jan 10 2017

Mathur R, et al.'s results suggest that Wnt signaling is critical for the maintenance and survival of MCL-ICs, and effective MCL therapy should aim to eliminate MCL-ICs through Wnt signaling inhibitors. [Read the Full Post]

Survivin as a therapeutic target in Sonic hedgehog-driven medulloblastoma

1287 | Jan 09 2017

Brun SN, et al.'s studies highlight the importance of Survivin in SHH-driven MB, and suggest that it may represent a novel therapeutic target in patients with this disease. [Read the Full Post]

Targeting hedgehog signaling reduces self-renewal in embryonal rhabdomyosarcoma

1371 | Jan 09 2017

Satheesha S, et al.'s work identifies novel functional aspects of hedgehog signaling in ERMS, redefines the rationale for its targeting as means to control ERMS self-renewal and underscores the importance of studying functional tumor heterogeneity in pediatric cancers. [Read the Full Post]

Human UDP-glucuronosyltransferase (UGT) 2B10: Validation of cotinine as a selective probe substrate, inhibition by UGT enzyme selective inhibitors and antidepressant and antipsychotic drugs, and structural determinants of enzyme inhibition

1644 | Jan 04 2017

In vitro-in vivo extrapolation of Pattanawongsa A, et al. indicates that these drugs may perpetrate inhibitory drug-drug interactions when coadministered with compounds that are cleared predominantly by UGT2B10. [Read the Full Post]

Hedgehog pathway is involved in nitidine chloride induced inhibition of epithelial-mesenchymal transition and cancer stem cells-like properties in breast cancer cells

1289 | Dec 09 2016

The study of Sun M et al. suggested that NC may be a potential anticancer agent for breast cancer. [Read the Full Post]

Cyclopiazonic acid, an inhibitor of calcium-dependent ATPases with antiviral activity against human respiratory syncytial virus

2900 | Nov 03 2016

Cui R et al. provided a new strategy for anti-RSV therapy via increasing intracellular calcium concentration. [Read the Full Post]

RNA polymerase III component Rpc9 regulates hematopoietic stem and progenitor cell maintenance in zebrafish

1122 | Sep 20 2016

Wei Y et al. illustrated that Rpc9, a component of Pol III, plays an important tissue-specific role in HSPC maintenance during zebrafish embryogenesis and might be conserved across vertebrates, including mammals. [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

1333 | 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]

PET imaging for chemokine receptor-4 detection in multiple myeloma

3500 | Mar 10 2015

Philipp-Abbrederis et al. developed a novel CXCR4 probe [68Ga]Pentixafor for mapping of CXCR4 expression density in vivo. [Read the Full Post]

ESKM, a novel therapeutic agent for sensitive and resistant PH+ leukemias

12281 | Jan 23 2015

Dubrovsky et al. developed an antibody, ESKM, which is therapeutically effective on acute and chronic leukemias in murine models. [Read the Full Post]

FTY720 is a first in class orally bioavailable

2241 | Feb 24 2014

The inhibitory effect of S1P is revered by various concentrations of FTY720. [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]

Dapagliflozin is a drug used to treat type 2 diabetes

2372 | Nov 27 2013

Dapagliflozin is not sensitive to hSGLT1 with a 1200-fold IC50. [Read the Full Post]

FTY720 is a first in class orally bioavailable compound

2261 | Nov 05 2013

The inhibitory effect of S1P is revered by various concentrations of FTY720, with IC50 effect of 173 nM. [Read the Full Post]

FTY720 is phosphorylated by sphingosine kinase type 2

2568 | Sep 30 2013

The inhibitory effect of S1P is revered by various concentrations of FTY720, with IC50 effect of 173 nM. [Read the Full Post]

NPS2143 is a novel potent and selective antagonist of Ca

2420 | Sep 10 2013

n rats, NPS 2143 results in a rapid 4- to 5-fold increase in plasma PTH levels and also a transient increase in plasma Ca2+ levels. [Read the Full Post]

FTY720 is an immunomodulating drug, approved for treating multiple sclerosis

2740 | Jun 03 2013

Fingolimod is a sphingosine 1-phosphate receptor modulator, which sequesters lymphocytes in lymph nodes, preventing them from contributing to an autoimmune reaction. [Read the Full Post]

Erismodegib is an orally bioavailable small molecule

2861 | Jan 07 2013

C Kit is a transmembrane receptor tyrosine kinase that binds stem cell factor SCF . CKit is encoded by the kit proto oncogene, localized to human chromosome and to mouse chromosome The c Kit SCF erismodegib interaction is critical for the survival and development of stem cells involved in hematopoiesis [Read the Full Post]

Sorafenib Tosylate is a multikinase inhibitor

2523 | Dec 13 2012

Sorafenib acute HCV infection leads to chronic infection in approximately 80% of cases. Chronic HCV infection is responsible for chronic hepatitis,which is complicated by cirrhosis in approximately 20% of cases. [Read the Full Post]

FTY720 – THE IMMUNE CELLS CONTROLLER

2658 | Apr 11 2012

FTY720: One of the extensively used immunoregulatory drug is Fingolimod, FTY720 is the code for this drug and it is a product of Novartis. The properties like anti-tumor actions and immunosuppressant activities made FTY720 Fingolimod a new hope against the debilitating diseases such as Multiple Sclerosis. FTY720 price for 100mg is around $40. Like many other compounds it is not soluble in water but a reasonable solubility of concentration of 100mg/ml can be attained using organic solvents such as DMSO and ethanol. Structurally FTY720 is an analogue of sphingosine molecule due to which this molecule has the capability to act on sphingosine-1-phosphate receptor, this report has been confirmed by gene deletion and reverse pharmacology studies. Various chemical modifications have been made with FTY720 in order to enhance its efficiency and to take it in clinical trials based on different diseases. If anyone wants to purchase FTY720 for laboratory and clinical uses one can order FTY720 to any FTY720 suppliers. IC50 of this drug is about 0.13 nM. [Read the Full Post]

The regulation of sphingosine-1-phosphate metabolism

3962 | Oct 20 2011

Sphingosine-1-phosphate (S1P) is a signaling sphingolipid and is also referred to as a bioactive lipid mediator. Functions of S1P are mediated by its binding to a class of G-protein coupled receptors of the S1P and Lysophospholipid (LPA) receptor families, and regulate a variety of cell signaling pathways, including cell growth, differentiation, survival, and apoptosis. Many factors in the metabolism pathway of S1P have been considered as potential targets for therapeutic intervention, including the inhibition of S1P activation of the G-protein coupled receptors. [Read the Full Post]

Brinkmann, V. (2007). "Sphingosine 1-phosphate receptors in health and disease: mechanistic insights from gene deletion studies and reverse pharmacology." Pharmacol Ther 115(1): 84-105.

3185 | Jul 22 2011

This article reviews S1P receptor subtypes and associated signaling pathways. The relationship between S1P receptors and different diseases is proved in the article. [Read the Full Post]

Rosen, H., P. J. Gonzalez-Cabrera, et al. (2009). "Sphingosine 1-phosphate receptor signaling." Annu Rev Biochem 78: 743-768.

3176 | Jun 10 2011

This review gives us the detail information about S1P receptors from different aspects including subtypes and Genetic Relationships, coupling Promiscuity and Its Consequences, design Features of the S1P Ligand System, S1P Receptor Signaling in Health and Disease and son on. [Read the Full Post]

Nelson, J., A. Bagnato, et al. (2003). "The endothelin axis: emerging role in cancer." Nat Rev Cancer 3(2): 110-116.

2920 | Mar 17 2011

The place of ET-receptor antagonists in cancer therapy for a range of malignancies merits further investigation. [Read the Full Post]