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Blog of Signaling Pathways

Safety evaluation of combination carboplatin and toceranib phosphate (Palladia) in tumour-bearing dogs: A phase I dose finding study

95 views | Jun 09 2019

Wouda RM et al. indicated the dose-limiting toxicity was neutropenia. Two dogs experienced a partial response, and 6 maintained stable disease. Combination carboplatin and toceranib chemotherapy was well-tolerated. Clinical benefit was observed in most cases. This protocol warrants further investigation in phase II/III trials. [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

84 views | 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]

CX-4945, a Selective Inhibitor of Casein Kinase 2, Synergizes with B Cell Receptor Signaling Inhibitors in Inducing Diffuse Large B Cell Lymphoma Cell Death

149 views | Jun 08 2019

Mandato E et al. suggested a role for CK2 downstream of the BCR in controlling survival pathways crucial for cell growth of different DLBCL subtypes. Also, the use of CX-4945 in combination with BCR signaling blockers could represent a novel rational therapeutic approach in the DLBCL. [Read the Full Post]

NK92-CD16 cells are cytotoxic to non-small cell lung cancer cell lines that have acquired resistance to tyrosine kinase inhibitors

195 views | Jun 08 2019

Park HR et al. suggested that combinational treatment with NK cell-based immunotherapy and cetuximab may be promising for patients with TKI-resistant NSCLC. [Read the Full Post]

Superior anti-tumor activity of the MDM2 antagonist idasanutlin and the Bcl-2 inhibitor venetoclax in p53 wild-type acute myeloid leukemia models

154 views | Jun 08 2019

Lehmann C et al provided functional and molecular insight on the superior anti-tumor activity of combined idasanutlin and venetoclax treatment in AML and support its further exploration in clinical studies. [Read the Full Post]

Midostaurin plus Chemotherapy for Acute Myeloid Leukemia with a FLT3 Mutation

146 views | Jun 07 2019

Stone RM et al. indicated the addition of the multitargeted kinase inhibitor midostaurin to standard chemotherapy significantly prolonged overall and event-free survival among patients with AML and a FLT3 mutation. [Read the Full Post]

Regulation of cisplatin-resistant head and neck squamous cell carcinoma by the SRC/ETS-1 signaling pathway

63 views | Jun 06 2019

Yang Z et al. demonstrated that the SRC/ETS-1 pathway plays a crucial role and could be a key therapeutic target in cisplatin-resistant HNSCC treatment. [Read the Full Post]

Elevating H3K27me3 level sensitizes colorectal cancer to oxaliplatin

126 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

101 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

70 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

109 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

69 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

69 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

134 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

208 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

81 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

161 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

195 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

75 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]