Blog of Signaling Pathways

Elevating H3K27me3 level sensitizes colorectal cancer to oxaliplatin

228 views | Jun 06 2019

Wang Q et al. suggested that elevating H3K27me3 level can improve drug sensitivity in CRC patients. [Read the Full Post]

Small molecules dorsomorphin and LDN-193189 inhibit myostatin/GDF8 signaling and promote functional myoblast differentiation

198 views | Jun 05 2019

Horbelt D et al. suggested these inhibitors as suitable tools to promote functional myogenesis. [Read the Full Post]

Differential effects of p38 MAP kinase inhibitors SB203580 and SB202190 on growth and migration of human MDA-MB-231 cancer cell line

153 views | Jun 05 2019

Düzgün ŞA et al. indicated the ERK1/2 phosphorylation level was not modified by low concentrations (1 or 5 µM) of SB202190 and SB203580; while a high concentration (50 µM) of both inhibitors caused significant reductions in the ERK1/2 phosphorylation. In addition, it was determined that both p38 MAPK inhibitors caused significant increases on the Ser15 phosphorylation of mutant p53 in MDA-MB-231 under these experimental conditions; while SB202190 was more potent than SB203580. [Read the Full Post]

The 3-Phosphoinositide-Dependent Protein Kinase 1 Inhibits Rod Photoreceptor Development

241 views | Jun 04 2019

Xing T et al. indicated that PDPK-1 and other intrinsic kinases downstream of IGF-1 are key regulators of rod photoreceptor formation. [Read the Full Post]

Inhibition of colony-stimulating-factor-1 signaling in vivo with the orally bioavailable cFMS kinase inhibitor GW2580

149 views | Jun 04 2019

Conway JG et al. showed that GW2580's selective inhibition of monocyte growth and bone degradation is consistent with cFMS kinase inhibition. The ability of GW2580 to chronically inhibit CSF-1 signaling through cFMS kinase in normal and tumor cells in vivo makes GW2580 a useful tool in assessing the role of cFMS kinase in normal and disease processes. [Read the Full Post]

Inhibitory Activities of Blasticidin S Derivatives on Aflatoxin Production by Aspergillus Flavus

149 views | Jun 03 2019

Yoshinari T et al. indicated that the inhibitory activity of BcS against aflatoxin production was enhanced by esterification of its carboxyl group and that the carboxymethyl ester derivative might be more suitable for practical use than BcS because of the specificity of the carboxymethyl ester derivative, which inhibited aflatoxin production more than BcS. [Read the Full Post]

Regulation of Skeletal Muscle DRP-1 and FIS-1 Protein Expression by IL-6 Signaling

274 views | Jun 03 2019

Fix DK et al. elevated IL-6 can directly induce DRP-1 and FIS-1 expression through gp130 signaling in cultured myotubes and skeletal muscle. Furthermore, ERK 1/2 signaling is necessary for the IL-6 induction of DRP-1 and FIS-1 expression in myotubes. [Read the Full Post]

ASP2215 in the treatment of relapsed/refractory acute myeloid leukemia with FLT3 mutation: background and design of the ADMIRAL trial

483 views | Jun 02 2019

Gorcea CM et al. showed that ASP2215 (gilteritinib) is a novel, dual FLT3/AXL inhibitor with promising early phase trial data (NCT02014558). [Read the Full Post]

Targeting FoxO1 with AS1842856 suppresses adipogenesis

161 views | Jun 02 2019

Zou P et al. suggested AS1842856 can be an anti-obesity agent that warrants further investigation. [Read the Full Post]

NVP-AUY922, a novel HSP90 inhibitor, inhibits the progression of malignant pheochromocytoma in vitro and in vivo

335 views | May 31 2019

Lian J et al. showed that NVP-AUY922 exhibits potent anti-PCC activities in vitro and in vivo and represents a promising therapeutic small molecule for treating malignant PCC. [Read the Full Post]

KD025 (SLx-2119) suppresses adipogenesis at intermediate stage in human adipose-derived stem cells

373 views | May 31 2019

Diep DTV et al. indicated that KD025suppresses adipocyte differentiation by modulation of key factors activated at the intermediate stage of differentiation, and not by inhibition of ROCK2. [Read the Full Post]

Strategies to Enhance Metabolic Stabilities

171 views | May 29 2019

Khatri B et al. noted that any chemical modification that helps in providing either local or global conformational rigidity to these macrocyclic peptides aids in improving their metabolic stability typically by slowing the cleavage kinetics by the proteases. [Read the Full Post]

Targeting ERK1/2 protein-serine/threonine kinases in human cancers

0 views | May 29 2019

Roskoski R Jr indicated that Ulixertinib, MK-8353, and GDC-0994 are orally effective, potent, and specific inhibitors of ERK1/2 that are in early clinical trials for the treatment of various advanced/metastatic solid tumors. These agents are effective against cell lines that are resistant to B-Raf and MEK1/2 inhibitor therapy. Although MK-8353 does not directly inhibit MEK1/2, it decreases the phosphorylation of ERK1/2 as well as the phosphorylation of RSK, an ERK1/2 substrate. The decrease in RSK phosphorylation appears to be a result of ERK inhibition and the decrease in ERK1/2 phosphorylation is related to the inability of MEK to catalyze the phosphorylation of the ERK-MK-8353 complex; these decreases characterize the ERK dual mechanism inhibition paradigm. Additional work will be required to determine whether ERK inhibitors will be successful in the clinic and are able to forestall the development of drug resistance of the MAP kinase pathway. [Read the Full Post]

In Vitro antiretroviral properties of S/GSK1349572, a next-generation HIV integrase inhibitor

178 views | May 28 2019

Kobayashi M et al. demonstrated that S/GSK1349572 would be classified as a next-generation drug in the integrase inhibitor class, with a resistance profile markedly different from that of first-generation integrase inhibitors. [Read the Full Post]

Chk1 inhibitor SCH 900776 enhances the antitumor activity of MLN4924 on pancreatic cancer

204 views | May 28 2019

Li JA et al. provided the preclinical evidence and the rationale of the combination therapy of MLN4924 with SCH 900776 or other Chk1 inhibitors to treat PC. [Read the Full Post]

The Potential Contribution of microRNAs in Anti-cancer Effects of Aurora Kinase Inhibitor (AZD1152-HQPA)

225 views | May 27 2019

Zekri A et al. showed for the first time the potential contribution of miRNAs in the anti-cancer effects of AZD1152-HQPA. [Read the Full Post]

CCI-779 (Temsirolimus) exhibits increased anti-tumor activity in low EGFR expressing HNSCC cell lines and is effective in cells with acquired resistance to cisplatin or cetuximab

135 views | May 27 2019

Niehr F et al. indicated that activity of CCI-779 in HNSCC cells harboring TP53 mutations and displaying a phenotype of cisplatin resistance suggests its clinical potential even in patients with dismal outcome after current standard treatment. Cetuximab/mTORi combinations might be useful for treatment of tumors with high expression of EGFR/p-EGFR and/or acquired cetuximab resistance. This combinatorial treatment modality needs further evaluation in future translational and clinical studies. [Read the Full Post]

Quantitative phosphoproteomic analysis of acquired cancer drug resistance to pazopanib and dasatinib

328 views | May 26 2019

Vyse S et al. provided a useful resource detailing the candidate signalling determinants of acquired TKI resistance; and reveals a therapeutic approach of inhibiting HSP90 function as a means of salvage therapy to overcome pazopanib and dasatinib resistance. [Read the Full Post]

Hemin-induced platelet activation and ferroptosis is mediated through ROS-driven proteasomal activity and inflammasome activation: Protection by Melatonin

176 views | May 26 2019

NaveenKumar SK et al. demonstrated an association of platelet activation/ferroptosis with proteasome activity and inflammasome activation. Although, high-throughput screening has recognized ferrostatin-1 (Fer-1) and liproxstatin-1 (Lip-1) as potent ferroptosis inhibitors, having an endogenous antioxidant such as MLT as ferroptosis inhibitor is of high interest. MLT is a well-known chronobiotic hormone that regulates the circadian rhythms in vertebrates. It is also known to exhibit potent antioxidant and ROS quenching capabilities. MLT can regulate fundamental cellular functions by exhibiting cytoprotective, oncostatic, antiaging, anti-venom, and immunomodulatory activities. The ROS scavenging capacity of MLT is key for its cytoprotective and anti-apoptotic properties. Considering the anti-ferroptotic and anti-apoptotic potentials MLT, it could be a promising clinical application to treat hemolytic, thrombotic and thrombocytopenic conditions. Therefore, we propose MLT as a pharmacological and therapeutic agent to inhibit ferroptosis and platelet activation. [Read the Full Post]

A Preclinical Model for Studying Herpes Simplex Virus Infection

0 views | May 25 2019

Tajpara P et al. present a previously unreported ex vivo HSV-1 infection model with abdominal human skin to test antiviral drugs, thus bridging the gap between in vitro and in vivo drug screening and providing a valuable preclinical platform for HSV research. [Read the Full Post]