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Blog of Signaling Pathways

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

1752 views | 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]

Targeting FGFR2 with alofanib (RPT835) shows potent activity in tumour models

1502 views | Apr 05 2017

Tsimafeyeu I et al showed that alofanib is a potent FGFR2 inhibitor and provide strong rationale for its evaluation in patients with FGFR2-driven cancers. [Read the Full Post]

GSK-3 directly regulates phospho-4EBP1 in renal cell carcinoma cell-line: an intrinsic subcellular mechanism for resistance to mTORC1 inhibition

732 views | Apr 04 2017

Ito H et al. found that GSK-3β/4EBP1 pathway might be an important subcellular mechanism as an inherent equipment for RCC cells to acquire clinical chemoresistance to mTORC1 inhibitors. [Read the Full Post]

Activation of the miR-34a/SIRT1/p53 Signaling Pathway Contributes to the Progress of Liver Fibrosis via Inducing Apoptosis in Hepatocytes but Not in HSCs

1341 views | Apr 04 2017

Tian XF et al. found that the miR-34a/SIRT1/p53 signaling pathway might be a promising therapeutic target for liver fibrosis. [Read the Full Post]

Distinct MicroRNA Expression Signatures of Porcine Induced Pluripotent Stem Cells under Mouse and Human ESC Culture Conditions

1176 views | Apr 04 2017

Zhang W et al. found that significant differences in the miRNA signatures of hpiPSCs and mpiPSCs under different pluripotent states that were derived from different culture conditions. [Read the Full Post]

Metabolic alterations and drug sensitivity of tyrosine kinase inhibitor resistant leukemia cells with a FLT3/ITD mutation

2452 views | Apr 03 2017

Huang A et al revealed a metabolic signature of sorafenib-resistant cells and suggests that glycolytic inhibition may override such resistance and warrant further clinical investigation. [Read the Full Post]

A high-throughput-compatible assay to measure the degradation of endogenous Huntingtin proteins

0 views | Apr 02 2017

Peng Wu et al established the first high-throughput-compatible assay capable of measuring endogenous, tag-free HTT degradation, providing a valuable tool for HD research and drug discovery. The method could be applied to other proteins and can facilitate research on other neurodegenerative disorders and proteinopathies. [Read the Full Post]

A synthetic cell-penetrating dominant-negative ATF5 peptide exerts anti-cancer activity against a broad spectrum of treatment resistant cancers

907 views | Apr 02 2017

Karpel-Massler G et al found the idea that CP-d/n-ATF5-S1, administered as a single reagent or in combination with other drugs, holds promise as an innovative, safe, and efficient antineoplastic agent against treatment-resistant cancers. Clin Cancer Res; 22(18); 4698-711. ©2016 AACR. [Read the Full Post]

iRGD-Decorated Polymeric Nanoparticles for the Efficient Delivery of Vandetanib to Hepatocellular Carcinoma: Preparation and in Vitro and in Vivo Evaluation

1232 views | Apr 01 2017

Wang J et al. demonstrated that reformulating targeted therapeutic agents in NPs permits their systemic administration and thus significantly improves the potency of currently available, orally delivered agents. [Read the Full Post]

Endoplasmic reticulum stress in mouse decidua during early pregnancy

0 views | Apr 01 2017

Xiao Wei Gu et al showed that ER stress induces DNA damage and polyploidization in stromal cells. In conclusion, our data suggest that the GRP78/Ire1/Xbp1 signaling pathway of ER stress-UPR is activated and involved in mouse decidualization. [Read the Full Post]

Heterogeneous Nuclear Ribonucleoprotein L is required for the survival and functional integrity of murine hematopoietic stem cells

0 views | Apr 01 2017

Gaudreau MC et al suggested that hnRNP L is critical for the survival and functional integrity of HSCs by restricting the activation of caspase-dependent death receptor pathways. [Read the Full Post]

A Novel mTORC1-Dependent, Akt-Independent Pathway Differentiates the Gut Tropism of Regulatory and Conventional CD4 T Cells

1032 views | Mar 31 2017

Chen LC et al. revealed a novel difference between ATRA signaling and chemokine receptor induction in Treg versus Tconv and provided a framework via which the migratory behavior of Treg versus Tconv might be regulated differentially for therapeutic purposes. [Read the Full Post]

Targeting the Neurokinin-1 Receptor Compromises Canonical Wnt Signaling in Hepatoblastoma

0 views | Mar 30 2017

Ilmer M et al revealed important insight into the molecular mechanisms of the SP/NK1R complex as a critical component in a model of pediatric liver cancer and may support the development of novel therapeutic interventions for HB and other Wnt-activated cancers. [Read the Full Post]

Chemokine CXCL13 mediates orofacial neuropathic pain via CXCR5/ERK pathway in the trigeminal ganglion of mice

923 views | Mar 29 2017

Zhang Q et al. found that targeting CXCL13/CXCR5/ERK/TNF-α and IL-1β pathway in the trigeminal ganglion may offer effective treatment for orofacial neuropathic pain. [Read the Full Post]

An RNA interference screen identifies new avenues for nephroprotection

0 views | Mar 29 2017

Zynda ER et al shed new light on the mechanisms of stress response in mammalian cells, and open new avenues to reduce the morbidity and mortality associated with renal injury. [Read the Full Post]

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

0 views | 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]

DNA Topoisomerase IIα contributes to the early steps of adipogenesis in 3T3-L1 cells

0 views | Mar 28 2017

Jacobsen RG et al. found that treatment of cancer with Topo II inhibitors may alter metabolic processes in the adipose tissue. [Read the Full Post]

A Repurposing Strategy for Hsp90 Inhibitors Demonstrates Their Potency against Filarial Nematodes

1 views | 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]

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

1044 views | 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 views | 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]