Blog of Signaling Pathways

The role of drug efflux and uptake transporters ABCB1 (P-gp), ABCG2 (BCRP) and OATP1A/1B and of CYP3A4 in the pharmacokinetics of the CDK inhibitor milciclib

208 views | Mar 26 2021

Alejandra Martínez-Chávez found that the low impact of OATP1 and CYP3A could be clinically favorable for milciclib, reducing the risks of unintended drug-drug interactions or interindividual variation in CYP3A4 activity. [Read the Full Post]

CEP131 Abrogates CHK1 Inhibitor-Induced Replication Defects and Is Associated with Unfavorable Outcome in Neuroblastoma

223 views | Mar 25 2021

Kiyohiro Ando et al. revealed that MDM2 was associated with CEP131 protein degradation, whereas overexpression of CEP131 accelerated neuroblastoma cell growth and exhibited resistance to CHK1i-induced replication defects. [Read the Full Post]

Pharmacological inhibition of IKKβ dampens NLRP3 inflammasome activation after priming in the human myeloid cell line THP-1

664 views | Mar 25 2021

Adeline Unterreiner et al. suggested that IκKβ might fulfill a dual role in coupling priming and activation of the NLRP3 inflammasome. [Read the Full Post]

FARP1 boosts CDC42 activity from integrin αvβ5 signaling and correlates with poor prognosis of advanced gastric cancer

241 views | Mar 24 2021

Takuro Hirano et al. suggested that the integrin αvβ5-FARP1-CDC42 axis played a crucial role in gastric cancer cell migration and invasion. [Read the Full Post]

Inhibition of HDAC6 by Tubastatin A reduces chondrocyte oxidative stress in chondrocytes and ameliorates mouse osteoarthritis by activating autophagy

443 views | Mar 24 2021

Zhonghai Shen et al. thought that HDAC6 inhibition prevented OA development, and HDAC6 could be applied as a potential therapeutic target for OA management. [Read the Full Post]

Addiction and the kynurenine pathway: A new dancing couple?

255 views | Mar 23 2021

Nuria Morales-Puerto et al. discussed ethanol, nicotine, cannabis, amphetamines, cocaine and opioids and new prospects in the drug research field were proposed [Read the Full Post]

Oxidative stress abrogates the degradation of KMT2D to promote degeneration in nucleus pulposus

414 views | Mar 23 2021

Wenbin Xu et al. approved that oxidative stress induced ROS production promote the process of NP degeneration by enhancing KMT2D mediated transcriptional regulation of matrix degeneration related genes during NP degeneration. [Read the Full Post]

A Three-Dimensional Organoid Culture Model to Assess the Influence of Chemicals on Morphogenetic Fusion

254 views | Mar 22 2021

David G Belair et al. demonstrated the utility of the in vitro fusion assay for identifying chemicals that disrupted human organoid morphogenesis in a scalable format amenable to toxicology screening. [Read the Full Post]

TAS-120 Overcomes Resistance to ATP-Competitive FGFR Inhibitors in Patients with FGFR2 Fusion-Positive Intrahepatic Cholangiocarcinoma

303 views | Mar 22 2021

Lipika Goyal et al. demonstrated that the irreversible FGFR inhibitor TAS-120 provided clinical benefit in patients with resistance to BGJ398 or Debio 1347 and overcomed several FGFR2 mutations in ICC models. [Read the Full Post]

Rational Design, synthesis and biological evaluation of novel triazole derivatives as potent and selective PRMT5 inhibitors with antitumor activity

358 views | Mar 21 2021

Kongkai Zhu et al. described the design, synthesis and biological evaluation of a series of novel, potent and selective PRMT5 inhibitors with antiproliferative activity against Z-138 mantle cell lymphoma cell line. [Read the Full Post]

Depletion of insulin-like growth factor 1 receptor increases radiosensitivity in colorectal cancer

554 views | Mar 21 2021

Yi Li et al. supported the notion that the radiosensitivity of radiation-resistant colorectal cancer cells could be enhanced by directly targeting IGF1R expression or activity. [Read the Full Post]

Targeting phosphoinositide 3-kinases and histone deacetylases in multiple myeloma

496 views | Mar 19 2021

Seiichi Okabe et al. suggested that the administration of CUDC-907 might be a powerful strategy against myeloma cells, to enhance the cytotoxic effects of proteasome inhibitors. [Read the Full Post]

AKT1-CREB stimulation of PDGFRα expression is pivotal for PTEN deficient tumor development

260 views | Mar 19 2021

Xiaofeng Wan et al. thought that activation of the AKT1-CREB-PDGFRα signaling pathway contributed to the tumor growth induced by PTEN deficiency and should be targeted for cancer treatment. [Read the Full Post]

Curcumin promotes cell cycle arrest and apoptosis of acute myeloid leukemia cells by inactivating AKT

341 views | Mar 18 2021

Hao Zhou et al. demonstrated that curcumin exerted anti‑AML roles by inactivating AKT. [Read the Full Post]

ALDH1A1 maintains the cancer stem-like cells properties of esophageal squamous cell carcinoma by activating the AKT signal pathway and interacting with β-catenin

218 views | Mar 18 2021

Wei Wang et al. found that ALDH1A1 expression maintained the CSC properties of ESCC cells. [Read the Full Post]

Beneficial effects of elafibranor on NASH in E3L.CETP mice and differences between mice and men

391 views | Mar 17 2021

Anita M van den Hoek et al. concluded that elafibranor might be particularly useful to reduce hepatic inflammation and could be a pharmacologically useful agent for human NASH, but probably in combination with other agents. [Read the Full Post]

Triple oral combination therapy with macitentan, riociguat, and selexipag for pulmonary arterial hypertension

232 views | Mar 17 2021

Mizuki Momoi et al. found that triple oral combination therapy with macitentan, riociguat, and selexipag sufficiently improved clinical parameters and was well tolerated in patients with PAH. [Read the Full Post]

Reversal of Cancer Multidrug Resistance (MDR) Mediated by ATP-Binding Cassette Transporter G2 (ABCG2) by AZ-628, a RAF Kinase Inhibitor

205 views | Mar 16 2021

Jing-Quan Wang et al. indicated that AZ-628 could be used in combination chemotherapy against ABCG2-mediated MDR in cancers. [Read the Full Post]

Cardioautonomic control in healthy singleton and twin pregnancies

562 views | Mar 16 2021

Victoria L Meah wt al. suggested that individuals with twin pregnancies had greater sympathetic and lower parasympathetic contributions to heart rate and that cardiac, but not vascular, autonomic control was impacted during twin compared to singleton pregnancy. [Read the Full Post]

Alpelisib: A Novel Therapy for Patients With PIK3CA- Mutated Metastatic Breast Cancer

183 views | Mar 15 2021

Tori Wilhoit et al. thought that inhibition of PI3K was a promising new approach to overcome resistance to endocrine therapy in breast cancer. [Read the Full Post]