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Blog of Signaling Pathways

Preclinical evaluation of drug combinations identifies co-inhibition of Bcl-2/XL/W and MDM2 as a potential therapy in uveal melanoma

0 views | Jan 16 2020

Clapes V et al. showed that inhibition of Bcl-2/XL/W sensitised the UM cell lines to other treatments encouraging investigation of the underlying mechanisms. [Read the Full Post]

Farnesoid X receptor agonist GW4064 ameliorates lipopolysaccharide-induced ileocolitis through TLR4/MyD88 pathway related mitochondrial dysfunction in mice

10 views | Jan 15 2020

Liu HM et al. demonstrated that central roles of FXR in coordinating regulation of both inflammation and mitochondrial dysfunction. We propose that GW4064 is promising therapeutic agent for treatment of ileocolitis. [Read the Full Post]

MK-8776, a novel chk1 kinase inhibitor, radiosensitizes p53-defective human tumor cells

10 views | Jan 15 2020

Bridges KA et al. indicated that MK-8776 radiosensitizes tumor cells by mechanisms that include abrogation of the G2 block and inhibition of DSB repair. Our findings support the clinical evaluation of MK-8776 in combination with radiation. [Read the Full Post]

Selective Cytotoxicity of the NAMPT Inhibitor FK866 Toward Gastric Cancer Cells With Markers of the Epithelial-Mesenchymal Transition, Due to Loss of NAPRT

10 views | Jan 14 2020

Lee J et al. showed that FK866 selectively kills gastric cancer cells with an EMT gene expression signature by inhibiting nicotinamide phosphoribosyltransferase in cells with NAPRT deficiency. Loss of NAPRT expression, frequently through promoter hypermethylation, is observed in many gastric tumors of the EMT subtype. FK866 might be used to treat patients with tumors of this subtype. [Read the Full Post]

Nicotinamide Phosphoribosyltransferase Inhibitor APO866 Prevents IL-1β-Induced Human Nucleus Pulposus Cell Degeneration via Autophagy

6 views | Jan 14 2020

Shi C et al. indicated that APO866 protects NP cells and induces autophagy by inhibiting IL-1β-induced NP cell degeneration and apoptosis, which may have therapeutic potential in IDD. [Read the Full Post]

Efficacy of pritelivir and acyclovir in the treatment of herpes simplex virus infections in a mouse model of herpes simplex encephalitis

9 views | Jan 13 2020

Quenelle DC et al. concluded pritelivir has potent and resistance-breaking antiviral efficacy with potential for the treatment of potentially life-threatening HSV type 1 and 2 infections, including herpes simplex encephalitis. [Read the Full Post]

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

0 views | Jan 13 2020

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

Suppression of human T cell proliferation by the caspase inhibitors, z-VAD-FMK and z-IETD-FMK is independent of their caspase inhibition properties

0 views | Jan 12 2020

Lawrence CP and Chow SC demonstrated that both z-VAD-FMK and z-IETD-FMK are immunosuppressive in vitro and inhibit T cell proliferation without blocking the processing of caspase-8 and caspase-3. [Read the Full Post]

Sulfoximines as ATR inhibitors: Analogs of VE-821

0 views | Jan 12 2020

Hendriks CMM et al. suggested that the sulfilimidoyl- and sulfoximidoyl-substituted analogs are efficient ATR inhibitors. [Read the Full Post]

Preparation and evaluation of 99mTc-labeled HYNIC-palbociclib analogs for cyclin-dependent kinase 4/6-positive tumor imaging

6 views | Jan 11 2020

Gan Q et al. indicated that 99mTc-tricine-TPPTS-L is a promising tumor imaging agent that targets CDK4/6. [Read the Full Post]

Adverse Drug Reactions Involving Protein Kinase Inhibitors: A French Pharmacovigilance Database Study Comparing Safety in Younger and Older Patients (≥ 75 years) with Cancer

6 views | Jan 11 2020

Clapes V et al. showed that PKI-related ADRs in older patients were similar to those in younger adults, except for vascular ADRs, which were significantly more frequent in the older population. [Read the Full Post]

Profiling of lincRNAs in human pluripotent stem cell derived forebrain neural progenitor cells

0 views | Jan 10 2020

Grassi DA et al. were able to identify many previously uncharacterized long intergenic non-coding RNAs that display dynamic expression during human forebrain neurogenesis. [Read the Full Post]

Glucocorticoid receptor antagonism overcomes resistance to BRAF inhibition in BRAFV600E-mutated metastatic melanoma

9 views | Jan 09 2020

Estrela JM et al. found that melanoma resistance is decreased if AKT and NF-κB signaling pathways are blocked. [Read the Full Post]

VCAM-1 Upregulation Contributes to Insensitivity of Vemurafenib in BRAF-Mutant Thyroid Cancer

11 views | Jan 09 2020

Chen S et al. demonstrated that VCAM-1 is upregulated in thyroid cancer cells treated with vemurafenib and contributes to vemurafenib resistance in BRAF-mutant thyroid cancer cells. [Read the Full Post]

17-AAG inhibits vemurafenib-associated MAP kinase activation and is synergistic with cellular immunotherapy in a murine melanoma model

23 views | Jan 08 2020

Joshi SS et al. indicated their sdudies support a role for 17-AAG and HSP90 inhibition in enhancing cellular immunotherapy for melanoma. [Read the Full Post]

JPH203, a selective L-type amino acid transporter 1 inhibitor, induces mitochondria-dependent apoptosis in Saos2 human osteosarcoma cells

10 views | 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]

BIRB 796 has Distinctive Anti-inflammatory Effects on Different Cell Types

13 views | Jan 07 2020

Ryoo S et al. suggested that the anti-inflammatory function of BIRB 796 depends on cell types. [Read the Full Post]

Tanespimycin as antitumor therapy

0 views | Jan 07 2020

Dimopoulos MA et al. indiacated that tanespimycin represents a promising new agent for the treatment of relapsed/refractory MM. Results of ongoing and future trials will determine the role of tanespimycin both in MM and other malignancies, including breast cancer. [Read the Full Post]

PI3K inhibitor LY294002, as opposed to wortmannin, enhances AKT phosphorylation in gemcitabine-resistant pancreatic cancer cells

24 views | Jan 06 2020

Wang Y et al. revealed that LY294002 displays the opposite effect on PI3K-dependent AKT phosphorylation, which maintains cell survival from the cytotoxicity introduced by LY294002 itself in GEM-resistant pancreatic cancer cells. We suggest that targeting the PI3K/AKT signaling pathway with inhibitors may be counterproductive for patients with PC who have acquired GEM-resistance. [Read the Full Post]

In vitro anti-osteoclastogenic activity of p38 inhibitor doramapimod via inhibiting migration of pre-osteoclasts and NFATc1 activity

0 views | Jan 06 2020

Moon SH et al. suggested anti-osteoclastogenic activity of doramapimod via inhibiting migration/fusion of pre-osteoclasts and NFATc1 activity. [Read the Full Post]