Background: Fear, stress, and anxiety-like behaviors originate from traumatic events in life. Stress response is managed by endocannabinoids in the body by limiting the uncontrolled retrieval of aversive memories. Pharmacotherapy-modulating endocannabinoids, especially anandamide, presents a promising tool ...
Pharmacological targeting of casein kinase 1δ suppresses oncogenic NRAS-driven melanoma Yalei Wen, Hui Wang, Xiao Yang, Yingjie Zhu, Mei Li, Xiuqing Ma, Lei Huang, Rui Wan, Caishi Zhang, Shengrong Li, Hongling Jia, Qin Guo, Xiaoyun Lu, Zhengqiu Li, Xiangchun Shen,...
This is the first demonstration that administering rapamycin late in life extends the lifespan of mice independently of their genetic background. Article CAS PubMed PubMed Central Google Scholar Baur, J. A. et al. Resveratrol improves health and survival of mice on a high-calorie diet. ...
Background: Therapeutic antibodies targeting EGFR have activity in advanced colorectal cancer, but results from clinical trials are inconsistent and the population in which most benefit is derived is uncertain. Our aim was to assess the ... MT Seymour,SR Brown,G Middleton,... - 《Lancet Oncology...
The inter- and intra-molecular heterogeneity of glioblastoma presents significant obstacles to effective clinical progression of novel treatments. Phenotypic drug screening is ideally suited to heterogeneous diseases, where targeting specific oncogenic drivers (such as EGFR) are broadly ineffective. Phenotypic...
Background Fabry disease (FD) is a genetic disorder resulting from deficiency of the lysosomal enzyme α-galactosidase A (α-Gal A), which leads to globotriaosylceramide (GL-3) accumulation in multiple tissues. We report on the safety and pharmacodynamics of migalastat hydrochloride, an investig...
In contrast to the type 1.5 inhibitors, type II inhibitors AZ-628 and LY3009120 show better inhibition of KRAS mutant cell lines. However, their potency in KRAS mutant cell lines was far weaker compared with the activity observed in the BRAFV600E mutant background (Figure 1A). Consistent ...
It was observed that most of the test compounds did not show any cytotoxic effect on MCF12A non-tumor cells, even at 500 µM concentration. A number of variables, including the kind of substitution occurring at the piperazinyl sites and the hereditary and pathological background of the cell...
Similarly, for SN12C cells, there were eight target classes that were significantly more efficacious in 2D monolayer cultures than 3D spheres (KDR, TOP2A, KIF11, EGFR, HDAC1, AURKA, SRC and CDK1). In addition, although they did not meet the criteria for difference by MAXR, TUBB, MET ...
The YAP–TEAD protein–protein interaction mediates YAP oncogenic functions downstream of the Hippo pathway. To date, available YAP–TEAD pharmacologic agents bind into the lipid pocket of TEAD, targeting the interaction indirectly via allosteric changes. However, the consequences of a direct pharmacolog...