Category

Archives

Blog of Signaling Pathways

Anti-inflammatory and chondroprotective effects of the S-adenosylhomocysteine hydrolase inhibitor 3-Deazaneplanocin A, in human articular chondrocytes

86 views | Feb 26 2019

Aury-Landas J et al. showed DZNep up-regulated cartilage specific genes, such as COL2A1 and SOX9, suggesting a chondroprotective effect of DZNep. DZNep exhibits anti-inflammatory effects, and regulates genes implicated in chondroprotective response in human articular chondrocytes, suggesting that inhibitors of S-adenosylmethionine-dependent methyltransferases could be effective treatments for OA. [Read the Full Post]

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

94 views | Feb 26 2019

Miranda TB et al. suggested 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]

Microglial modulation through colony-stimulating factor-1 receptor inhibition attenuates demyelination

76 views | Feb 25 2019

Wies Mancini VSB et al. showed that BLZ945 induced a significant reduction in the number of microglia. Preventive BLZ945 treatment attenuated demyelination in the acute CPZ model, mainly in cortex and external capsule. In contrast, BLZ945 treatment in the acute CPZ model failed to protect myelin or foster remyelination in myelin-rich areas, which may respond to a loss in microglial phagocytic capacity and the consequent impairment in oligodendroglial differentiation. Preventive and therapeutic BLZ945 treatment promoted remyelination and neuroprotection in the chronic model. These results could be potentially transferred to the treatment of progressive forms of MS. [Read the Full Post]

RSL3 and Erastin differentially regulate redox signaling to promote Smac mimetic-induced cell death

93 views | Feb 25 2019

Dächert J et al. indicated that RSL3/BV6 and Erastin/BV6 differentially regulate redox signaling and cell death in ALL cells. While RSL3/BV6 cotreatment induces ferroptotic cell death, Erastin/BV6 stimulates oxidative cell death independently of iron. These findings have important implications for the therapeutic targeting of redox signaling to enhance Smac mimetic-induced cell death in ALL. [Read the Full Post]

Tanespimycin as antitumor therapy

229 views | Feb 24 2019

Dimopoulos MA et al. showed 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]

Design and molecular modeling of novel P38α MAPK inhibitors targeting breast cancer, synthesized from oxygen heterocyclic natural compounds

654 views | Feb 24 2019

Abdelhafez OM et al. indicated these promising results of cytotoxic activity and significant inhibition of p38α MAP kinase, were confirmed by exploring the effect of benzofuran derivative (18) on the apoptotic induction and cell cycle progression of MCF-7 cell line. Compound 18 induced preG1 apoptosis and cell growth arrest at G2/M phase preventing the mitotic cycle. Moreover it activated the caspase-7 which executes apoptosis. Molecular docking study was carried out using GOLD program to predict the mode of binding interaction of the synthesized compounds into the target p38α MAPK. Additionally, the physicochemical properties and ADME parameters of compound 18 were examined in silico to investigate its drug-likeness. [Read the Full Post]

Effects of cancer-associated point mutations on the structure, function, and stability of succinate dehydrogenase A

210 views | Feb 22 2019

Cao ZF et al. provided information important for understanding the molecular mechanisms of SDHA mutations in tumors. [Read the Full Post]

Crenolanib is a selective type I pan-FLT3 inhibitor

152 views | Feb 21 2019

Smith CC et al. showed that Crenolanib has significant promise for achieving deep and durable responses in FLT3-mutant AML, and may have a profound impact upon future medicinal chemistry efforts in oncology. [Read the Full Post]

Potent in vivo lung cancer Wnt signaling inhibition via cyclodextrin-LGK974 inclusion complexes

170 views | Feb 21 2019

Guimaraes PPG et al. indicated the development of these complexes enables safer and repeated oral or parenteral administration of Wnt signaling inhibitors, which hold promise for the treatment of multiple types of malignancies. [Read the Full Post]

Practice patterns and outcomes with the use of regorafenib in metastatic colorectal cancer: Results from the Regorafenib in Metastatic colorectal cancer - An Indian exploratory analysis study

242 views | Feb 19 2019

Ramaswamy A et al. indicated duration of treatment with regorafenib as an efficacy end point in this study is similar to available data from other regions as it is the side effect profile. [Read the Full Post]

The mTORC1/2 Inhibitor AZD8055 Strengthens the Efficiency of the MEK Inhibitor Trametinib to Reduce the Mcl-1/[Bim and Puma] ratio and to Sensitize Ovarian Carcinoma Cells to ABT-737

104 views | Feb 19 2019

Pétigny-Lechartier C et al. indicated the three-drug combination was also very efficient when replacing AZD8055 by the pan-Akt inhibitor MK-2206. This study thus proposes original multitargeted strategies and may have important implications for the design of novel approaches for ovarian cancer treatment. [Read the Full Post]

A natural compound, aristoyagonine, is identified as a potent bromodomain inhibitor by mid-throughput screening

142 views | Feb 18 2019

Kim YH et al. tested Brd4 inhibitors in gastric cancer cell lines, and found that aristoyagonine exerted cytotoxicity not only in I-BET-762-sensitive cancer cells, but also in I-BET-762-resistant cancer cells. This is the first paper to describe a natural compound as a Brd4 bromodomain inhibitor. [Read the Full Post]

Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial

231 views | Feb 18 2019

Bruix J et al. indicated that regorafenib is the only systemic treatment shown to provide survival benefit in HCC patients progressing on sorafenib treatment. Future trials should explore combinations of regorafenib with other systemic agents and third-line treatments for patients who fail or who do not tolerate the sequence of sorafenib and regorafenib. [Read the Full Post]

Dual mTORC1/2 inhibition by INK-128 results in antitumor activity in preclinical models of osteosarcoma

116 views | Feb 17 2019

Jiang H et al. showed that INK-128 exerts potent anti-OS activity in vitro and in vivo. INK-128might be further investigated as a novel anti-OS agent. [Read the Full Post]

Dual mTORC1/2 inhibition by INK-128 results in antitumor activity in preclinical models of osteosarcoma

0 views | Feb 17 2019

Jiang H et al. showed that INK-128 exerts potent anti-OS activity in vitro and in vivo. INK-128might be further investigated as a novel anti-OS agent. [Read the Full Post]

Loss of ARID1A expression leads to sensitivity to ROS-inducing agent elesclomol in gynecologic cancer cells

0 views | Feb 16 2019

Kwan SY et al. demonstrated for the first time that loss of ARID1A leads to accumulation of ROS and suggest that elesclomol may be used to target ARID1A-mutant gynecologic cancer cells. [Read the Full Post]

ABCB1 Mediates Cabazitaxel-Docetaxel Cross-Resistance in Advanced Prostate Cancer

142 views | Feb 16 2019

Lombard AP et al. suggested the potential in using combinations of antiandrogens with cabazitaxel for increased effect in treating advanced CRPC. [Read the Full Post]

Ionizing Radiation Blocks Hair Cell Regeneration in Zebrafish Lateral Line Neuromasts by Preventing Wnt Signaling

199 views | Feb 15 2019

Li R et al. suggested that radiation suppressed hair cell regeneration in zebrafish lateral line neuromasts through inhibition of Wnt signaling in supporting cells possibly by secreting anti-proliferation factors like dkk2. Maintaining a healthy supporting cell pool is vital for regeneration of hair cells. [Read the Full Post]

The Phosphodiesterase 10A Inhibitor PF-2545920 Enhances Hippocampal Excitability and Seizure Activity Involving the Upregulation of GluA1 and NR2A in Post-synaptic Densities

110 views | Feb 15 2019

Zhang Y et al. suggested it would be detrimental to use the drug in seizure patients and might cause neuronal hyperexcitability in non-epileptic individuals. [Read the Full Post]

CX-5461 is a DNA G-quadruplex stabilizer with selective lethality in BRCA1/2 deficient tumours

88 views | Feb 14 2019

Xu H et al. indicated these data strengthen the concept of G4 targeting as a therapeutic approach, specifically for targeting HR and NHEJ deficient cancers and other tumours deficient for DNA damage repair. [Read the Full Post]