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Blog of Signaling Pathways

Tipifarnib prevents development of hypoxia-induced pulmonary hypertension

0 views | Dec 02 2019

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

Anti-myeloma effect of pharmacological inhibition of Notch/gamma-secretase with RO4929097 is mediated by modulation of tumor microenvironment

277 views | Dec 02 2019

Pisklakova A et al. indicated that targeting Notch may be considered as a new strategy to be tested for MM therapy. [Read the Full Post]

3-Deazaneplanocin A and neplanocin A analogues and their effects on apoptotic cell death

128 views | Dec 01 2019

Tam EK et al. identified three compounds that show similar activities to DzNep. Two of these compounds show good pharmacokinetics and safety profiles. Attempts to correlate the observed synergistic apoptotic activities with measured S-adenosylhomocysteine hydrolase (SAHH) inhibitory activities suggest that the apoptotic activity of DzNep might not be directly due to its inhibition of SAHH. [Read the Full Post]

DZNep is a global histone methylation inhibitor that reactivates developmental genes not silenced by DNA methylation

0 views | Dec 01 2019

Miranda TB et al. found that upon removal of DZNep, gene expression is reduced to its original state. This suggests that there is a homeostatic mechanism that returns the histone modifications to their "ground state" after DZNep treatment. Our data show the strong need for further development of histone methylation inhibitors. [Read the Full Post]

SB202190 inhibits endothelial cell apoptosis via induction of autophagy and heme oxygenase-1

155 views | Nov 29 2019

Schwartz M et al. opposed HO-1 to contribute to SB202190-mediated increases in metabolic activity and autophagy, respectively. [Read the Full Post]

Tri-methylation of H3K79 is decreased in TGF-β1-induced epithelial-to-mesenchymal transition in lung cancer

396 views | Nov 29 2019

Evanno E et al. showed that histone methylation was modified during EMT, and combination of epigenetic compounds with conventional or targeted chemotherapy might contribute to reduce metastasis and to enhance clinical responses. [Read the Full Post]

Barasertib (AZD1152), a Small Molecule Aurora B Inhibitor, Inhibits the Growth of SCLC Cell Lines In Vitro and In Vivo

0 views | Nov 28 2019

Helfrich BA et al. suggested that SCLC tumors with cMYC amplification/high gene expression will frequently respond to Aurora B inhibitors and that clinical studies coupled with predictive biomarkers are indicated. [Read the Full Post]

Generation of pig induced pluripotent stem cells using an extended pluripotent stem cell culture system

207 views | Nov 27 2019

Xu J et al. demonstrated that stable iPS cells could be generated in LCDM medium, which could give rise to both embryonic and extraembryonic cells in vivo. However, the efficiency and level of chimeric contribution of pig LCDM-iPS cells were found low. [Read the Full Post]

Isolation of induced pluripotent stem cell-derived endothelial progenitor cells from sac-like structures

221 views | Nov 27 2019

Aoki H et al. improved regenerative medicine and facilitate basic studies on the endothelial lineage. [Read the Full Post]

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

174 views | Nov 25 2019

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

MCL-1 antagonism enhances the anti-invasive effects of dasatinib in pancreatic adenocarcinoma

105 views | Nov 25 2019

Castillo L et al. suggested that MCL-1 antagonism, while reducing cell viability, may have an additional benefit in increasing the antimetastatic efficacy of dasatinib for the treatment of PDAC. [Read the Full Post]

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

180 views | Nov 24 2019

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

Y-27632 preserves epidermal integrity in a human skin organ-culture (hSOC) system by regulating AKT and ERK signaling pathways

190 views | Nov 23 2019

Zhang X et al. found that Y-227632 can maintain skin epidermal integrity through regulation of AKT and ERK activity in the hSOC. [Read the Full Post]

Isovitexin Suppresses Cancer Stemness Property And Induces Apoptosis Of Osteosarcoma Cells By Disruption Of The DNMT1/miR-34a/Bcl-2 Axis

101 views | Nov 23 2019

Liang X et al. suggested that ISOV-mediated epigenetic regulation involved the DNMT1/miR-34a/Bcl-2 axis and caused the suppression of stemness and induction of apoptosis in the spheres derived from OS cells. The data indicated that ISOV exhibited a novel efficient potential for the treatment of OS. [Read the Full Post]

Salidroside attenuates dextran sulfate sodium-induced colitis in mice via SIRT1/FoxOs signaling pathway

196 views | Nov 22 2019

Li H et al. manifested that Sal may protect colitis mice by activating the SIRT1/FoxOs pathway, which is related to oxidative stress and apoptosis in colon tissues. [Read the Full Post]

Combinational therapeutic targeting of BRD4 and CDK7 synergistically induces anticancer effects in head and neck squamous cell carcinoma

119 views | Nov 21 2019

Zhang W et al. revealed a novel therapeutic strategy of pharmacological inhibitions of BRD4 and CDK7 against HNSCC. [Read the Full Post]

U0126 attenuates ischemia/reperfusion-induced apoptosis and autophagy in myocardium through MEK/ERK/EGR-1 pathway

147 views | Nov 20 2019

Wang A et al. suggested that U0126 may protect against H/R injury by preventing H/R-induced myocardium apoptosis and autophagy via the MEK/ERK/EGR-1 pathway, and may be a potential therapeutic approach for attenuating myocardial I/R injury. [Read the Full Post]

PK-PD modeling of combination efficacy effect from administration of the MEK inhibitor GDC-0973 and PI3K inhibitor GDC-0941 in A2058 xenografts

116 views | Nov 20 2019

Choo EF et al. suggested that, based on minimal data, it is possible to predict the effects of various combinations preclinically and also assess the potential clinical efficacy of combinations using human pharmacokinetic inputs. [Read the Full Post]

A Genome-Wide CRISPR Screen Identifies Genes Critical for Resistance to FLT3 Inhibitor AC220

0 views | Nov 19 2019

Hou P et al. identified novel genes whose loss of function conferred resistance to a selective FLT3 inhibitor, providing new insight into signaling pathways that contribute to acquired resistance in AML. [Read the Full Post]

Activation of MAPK signalling results in resistance to saracatinib (AZD0530) in ovarian cancer

181 views | Nov 18 2019

McGivern N et al. provided a preclinical rationale for the combination of SRC and MEK inhibitors in the treatment of ovarian cancer, and also highlights the need for biomarker driven patient selection for clinical trials. [Read the Full Post]