keyword
MENU ▼
Read by QxMD icon Read
search

Gsk3 Inhibitor

keyword
https://www.readbyqxmd.com/read/28714403/gsk3-inhibitors-in-the-therapeutic-development-of-diabetes-cancer-and-neurodegeneration-past-present-and-future
#1
Mudasir Maqbool, Nasimul Hoda
GSK3 has gained a considerable attention of researchers in the late 1970s as an inevitable drug target to treat diabetes. Furthermore, it was found to have a key role in the development of diseases like cancer and neurodegeneration (ND). A broad spectrum of GSK3 inhibitors have been discovered from time to time in order to curb these diseases. Inhibition of GSK3 by insulin boosts the dephosphorylation of glycogen synthase, hence its activation to convert UDP glucose into glycogen. Lack of insulin and insulin-resistance is supposed to be the cause of type 2 diabetes (Diabetes mellitus)...
July 14, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28713919/ganetespib-induces-g2-m-cell-cycle-arrest-and-apoptosis-in-gastric-cancer-cells-through-targeting-of-receptor-tyrosine-kinase-signaling
#2
Harry Lee, Nipun Saini, Amanda B Parris, Ming Zhao, Xiaohe Yang
Heat shock protein 90 (HSP90) regulates several important cellular processes via its repertoire of 'client proteins'. These client proteins have been found to play fundamental roles in signal transduction, cell proliferation, cell cycle progression and survival, as well as other features of malignant cells, such as invasion, tumor angiogenesis and metastasis. Thus, HSP90 is an emerging target for cancer therapy. To this end, we evaluated ganetespib (STA-9090), a novel and potent HSP90 inhibitor, for its activity in gastric cancer cell lines...
July 13, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28710230/the-tissue-reconstructing-ability-of-colon-cscs-is-enhanced-by-fk506-and-suppressed-by-gsk3-inhibition
#3
Ryo Ishida, Michiyo Koyanagi-Aoi, Nobu Oshima, Yoshihiro Kakeji, Takashi Aoi
Cancer stem cells (CSCs) are capable of reconstructing cancer tissues, are involved in both recurrence and metastasis, and contribute to therapeutic resistance. Therefore, elucidating the molecular mechanism in CSCs is important to successfully treat unresectable cancers. Previously we observed that colon cancer stem-like cells can be induced from human colon cancer cell lines by retrovirally introducing OCT3/4, SOX2 and KLF4, and we have designated such cells as induced cancer stem cells (iCSCs). In the current study, we used iCSCs to evaluate the molecular mechanism of colon CSCs and developed new methods to control them...
July 14, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28698144/inhibiting-glycogen-synthase-kinase-3-and-transforming-growth-factor-%C3%AE-signaling-to-promote-epithelial-transition-of-human-adipose-mesenchymal-stem-cells
#4
Melina Setiawan, Xiao-Wei Tan, Tze-Wei Goh, Gary Hin-Fai Yam, Jodhbir S Mehta
BACKGROUND: This study was aimed to investigate the epithelial differentiation of human adipose-derived mesenchymal stem cells (ADSCs) by inhibiting glycogen synthase kinase-3 (GSK3) and transforming growth factor β (TGFβ) signaling. METHODS AND RESULTS: STEMPRO human ADSCs at passage 2 were treated with CHIR99021 (GSK3 inhibitor), E-616452 (TGFβ1 receptor kinase inhibitor), A-83-01 (TGFβ type 1 receptor inhibitor), valproic acid (histone deacetylase inhibitor), tranylcypromine (monoamine oxidase inhibitor) and all-trans retinoic acid for 72 h...
July 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28662520/regulation-of-ap-1-by-mapk-signaling-in-metal-stressed-sea-anemone
#5
Maayan Agron, Vera Brekhman, David Morgenstern, Tamar Lotan
BACKGROUND/AIMS: AP-1 transcription factor plays a conserved role in the immediate response to stress. Activation of AP-1 members jun and fos is mediated by complex signaling cascades to control cell proliferation and survival. To understand the evolution of this broadly-shared pathway, we studied AP-1 regulation by MAPK signaling in a basal metazoan. METHODS: Metal- stressed cnidarian Nematostella vectensis anemones were tested with kinase inhibitors and analyzed for gene expression levels and protein phosphorylation...
June 27, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28638078/the-stress-response-factor-daf-16-foxo-is-required-for-multiple-compound-families-to-prolong-the-function-of-neurons-with-huntington-s-disease
#6
Francesca Farina, Emmanuel Lambert, Lucie Commeau, François-Xavier Lejeune, Nathalie Roudier, Cosima Fonte, J Alex Parker, Jacques Boddaert, Marc Verny, Etienne-Emile Baulieu, Christian Neri
Helping neurons to compensate for proteotoxic stress and maintain function over time (neuronal compensation) has therapeutic potential in aging and neurodegenerative disease. The stress response factor FOXO3 is neuroprotective in models of Huntington's disease (HD), Parkinson's disease and motor-neuron diseases. Neuroprotective compounds acting in a FOXO-dependent manner could thus constitute bona fide drugs for promoting neuronal compensation. However, whether FOXO-dependent neuroprotection is a common feature of several compound families remains unknown...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28625976/a-genome-wide-crispr-screen-identifies-genes-critical-for-resistance-to-flt3-inhibitor-ac220
#7
Panpan Hou, Chao Wu, Yuchen Wang, Rui Qi, Dheeraj Bhavanasi, Zhixiang Zuo, Cedric Dos Santos, Shuliang Chen, Yu Chen, Hong Zheng, Hong Wang, Alexander E Perl, Deyin Guo, Jian Huang
Acute myeloid leukemia (AML) is a malignant hematopoietic disease and the most common type of acute leukemia in adults. The mechanisms underlying drug resistance in AML are poorly understood. Activating mutations in FMS-like tyrosine kinase 3 (FLT3) are the most common molecular abnormality in AML. Quizartinib (AC220) is a potent and selective second-generation inhibitor of FLT3. It is in clinical trials for the treatment of relapsed or refractory FLT3-ITD-positive and -negative AML patients and as maintenance therapy...
June 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28606794/antifibrotic-actions-of-peroxisome-proliferator-activated-receptor-%C3%AE-ligands-in-corneal-fibroblasts-are-mediated-by-%C3%AE-catenin-regulated-pathways
#8
Kye-Im Jeon, Richard P Phipps, Patricia J Sime, Krystel R Huxlin
Wound healing after corneal injury typically involves fibrosis, with transforming growth factor β1 (TGF-β1) as one of its strongest mediators. A class of small molecules-peroxisome proliferator-activated receptor γ (PPARγ) ligands-exert potent antifibrotic effects in the cornea by blocking phosphorylation of p38 mitogen-activated protein kinase (MAPK). However, why this blocks fibrosis remains unknown. Herein, we show that PPARγ ligands (rosiglitazone, troglitazone, and 15-deoxy-Δ12,14-prostaglandin J2) decrease levels of β-catenin...
June 10, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28602697/gsk3-inhibitor-ar-a014418-promotes-osteogenic-differentiation-of-human-adipose-derived-stem-cells-via-erk-and-mtorc2-akt-signaling-pathway
#9
Min Zhang, Ping Zhang, Yunsong Liu, Yongsheng Zhou
Small molecule-based bone tissue engineering is emerging as a promising strategy for bone defects restoration. In this study, we intended to identify the roles and mechanisms of AR-A014418, a highly selective inhibitor of GSK3, on the osteogenic differentiation. We found that AR-A014418 exhibited a dose-dependent effect on osteogenic differentiation of human adipose-derived stem cells (hASCs). hASCs treated with AR-A014418 showed higher activity of ERK and mTORC2/Akt signaling. Administration of ERK inhibitor U0126 or knockdown of RICTOR by siRNA attenuated AR-A014418 induced osteogenic differentiation of hASCs...
August 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28577307/disrupting-interactions-between-%C3%AE-catenin-and-activating-tcfs-reconstitutes-ground-state-pluripotency-in-mouse-embryonic-stem-cells
#10
Abil Saj, Sujash S Chatterjee, Bowen Zhu, Engin Cukuroglu, Tenzin Gocha, Xiaoqian Zhang, Jonathan Göke, Ramanuj DasGupta
The 2i-media, composed of two small molecule inhibitors (PD0325901 and CHIR99021) against MEK and GSK3-kinases, respectively, is known to establish naïve ground state pluripotency in mouse embryonic stem cells (mESCs). These inhibitors block MEK-mediated differentiation, while driving β-catenin dependent de-repression of pluripotency promoting targets. However, accumulating evidence suggest that β-catenin's association with activating TCFs (TCF7 and TCF7L2) can induce expression of several lineage-specific prodifferentiation genes...
August 2017: Stem Cells
https://www.readbyqxmd.com/read/28575156/consequences-of-endogenous-and-exogenous-wnt-signaling-for-development-in-the-preimplantation-bovine-embryo%C3%A2
#11
Paula Tribulo, Beatriz Caetano da Silva Leão, Khoboso C Lehloenya, Gisele Zoccal Mingoti, Peter J Hansen
Although WNT signaling regulates several developmental processes, its specific role during preimplantation development remains unclear. The present aim was to evaluate the consequences of activation and inhibition of β-catenin (CTNNB1) dependent and -independent WNT signaling in the bovine preimplantation embryo. Activation of CTNNB1 mediated WNT signaling by the agonist 2-amino-4-(3,4-(methylenedioxy)benzylamino)-6-(3-methoxyphenyl)pyrimidine (AMBMP) and a glycogen synthase kinase 3 (GSK3) inhibitor reduced development to the blastocyst stage...
May 30, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28574599/inhibition-of-glycogen-synthase-kinase-3-beta-gsk3%C3%AE-suppresses-the-progression-of-esophageal-squamous-cell-carcinoma-by-modifying-stat3-activity
#12
Shegan Gao, Shuoguo Li, Xiaoxian Duan, Zhen Gu, Zhikun Ma, Xiang Yuan, Xiaoshan Feng, Huizhi Wang
While GSK3β has been reported to have contrasting effects on the progression of different tumors, its possible functions in esophageal squamous cell carcinoma (ESCC) and the related molecular mechanisms remain unknown. Here, we investigated the expression, function, and molecular mechanism of GSK3β in the development of ESCC in vitro and in vivo. Though the expression of total GSK3β was significantly increased, the phosphorylated (inactivated) form of GSK3β (Ser9) was concurrently decreased in the cancerous tissues of patients with ESCC compared with controls, suggesting that GSK3β activity was enhanced in cancerous tissues...
June 2, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28566716/glycogen-synthase-kinase-3%C3%AE-inhibitors-prevent-hepatitis-c-virus-release-assembly-through-perturbation-of-lipid-metabolism
#13
Mohammed A Sarhan, Mohamed S Abdel-Hakeem, Andrew L Mason, D Lorne Tyrrell, Michael Houghton
Direct acting antivirals against hepatitis C virus (HCV) have markedly improved cure rates in the past few years. However, they are expensive, with only few targeting host cell factors, and affecting virus assembly and release. Huh7.5 cells infected with a JFH-1 clone of HCV were treated with two different glycogen synthase kinase (GSK3)-β inhibitors; AR-A014418 and lithium chloride. Intra- and extracellular HCV virions and specific infectivity was determined using real-time RT-PCR and TCID50, and changes in lipid production were identified by enzyme-linked immunoassay and mass spectrometry analyses...
May 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28556462/gsk3-activity-regulates-rhythms-in-hippocampal-clock-gene-expression-and-synaptic-plasticity
#14
Rachel C Besing, Courtney O Rogers, Jodi R Paul, Lauren M Hablitz, Russell L Johnson, Lori L McMahon, Karen L Gamble
Hippocampal rhythms in clock gene expression, enzymatic activity, and long-term potentiation (LTP) are thought to underlie day-night differences in memory acquisition and recall. Glycogen synthase kinase 3-beta (GSK3β) is a known regulator of hippocampal function, and inhibitory phosphorylation of GSK3β exhibits region-specific differences over the light-dark cycle. Here, we sought to determine whether phosphorylation of both GSK3α and GSK3β isoforms has an endogenous circadian rhythm in specific areas of the hippocampus and whether chronic inhibition or activation alters the molecular clock and hippocampal plasticity (LTP)...
August 2017: Hippocampus
https://www.readbyqxmd.com/read/28546219/inos-derived-nitric-oxide-induces-integrin-linked-kinase-endocytic-lysosome-mediated-degradation-in-the-vascular-endothelium
#15
Paula Reventun, Matilde Alique, Irene Cuadrado, Susana Márquez, Rocío Toro, Carlos Zaragoza, Marta Saura
OBJECTIVE: ILK (integrin-linked kinase) plays a key role in controlling vasomotor tone and is decreased in atherosclerosis. The objective of this study is to test whether nitric oxide (NO) regulates ILK in vascular remodeling. APPROACH AND RESULTS: We found a striking correlation between increased levels of inducible nitric oxide and decreased ILK levels in human atherosclerosis and in a mouse model of vascular remodeling (carotid artery ligation) comparing with iNOS (inducible NO synthase) knockout mice...
July 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28545044/differentiation-of-spontaneously-contracting-cardiomyocytes-from-non-virally-reprogrammed-human-amniotic-fluid-stem-cells
#16
Aaron J Velasquez-Mao, Christopher J M Tsao, Madeline N Monroe, Xavier Legras, Beatrice Bissig-Choisat, Karl-Dimiter Bissig, Rodrigo Ruano, Jeffrey G Jacot
Congenital heart defects are the most common birth defect. The limiting factor in tissue engineering repair strategies is an autologous source of functional cardiomyocytes. Amniotic fluid contains an ideal cell source for prenatal harvest and use in correction of congenital heart defects. This study aims to investigate the potential of amniotic fluid-derived stem cells (AFSC) to undergo non-viral reprogramming into induced pluripotent stem cells (iPSC) followed by growth-factor-free differentiation into functional cardiomyocytes...
2017: PloS One
https://www.readbyqxmd.com/read/28504720/a-clinical-drug-library-screen-identifies-clobetasol-propionate-as-an-nrf2-inhibitor-with-potential-therapeutic-efficacy-in-keap1-mutant-lung-cancer
#17
E-J Choi, B-J Jung, S-H Lee, H-S Yoo, E-A Shin, H-J Ko, S Chang, S-Y Kim, S-M Jeon
The Kelch-like ECH-associated protein 1 (KEAP1)-nuclear factor E2-related factor 2 (NRF2)pathway has a central role in cellular antioxidant defense. NRF2 activation due to KEAP1 or NRF2 mutations occurs frequently in many cancers, suggesting that NRF2 inhibition could be a promising therapeutic strategy. However, no potent NRF2 inhibitors are clinically available to date. To develop potent NRF2 inhibitors for therapeutic purpose, we screened ~4000 clinical compounds and determined clobetasol propionate (CP) as the most potent NRF2 inhibitor...
May 15, 2017: Oncogene
https://www.readbyqxmd.com/read/28499784/gsk-3-as-a-novel-prognostic-indicator-in-leukemia
#18
REVIEW
Peter P Ruvolo
While leukemias represent a diverse set of diseases with malignant cells derived from myeloid or lymphoid origin, a common feature is the dysregulation of signal transduction pathways that influence leukemogeneisis, promote drug resistance, and favor leukemia stem cells. Mutations in PI3K, PTEN, RAS, or other upstream regulators can activate the AKT kinase which has central roles in supporting cell proliferation and survival. A major target of AKT is Glycogen Synthase Kinase 3 (GSK3). GSK3 has two isoforms (alpha and beta) that were studied as regulators of metabolism but emerged as central players in cancer in the early 1990s...
May 8, 2017: Advances in Biological Regulation
https://www.readbyqxmd.com/read/28486050/the-cdk4-6-inhibitor-palbociclib-synergizes-with-irinotecan-to-promote-colorectal-cancer-cell-death-under-hypoxia
#19
Jun Zhang, Lanlan Zhou, Shuai Zhao, David T Dicker, Wafik S El-Deiry
Hypoxia is an inherent impediment to cancer therapy. Palbociclib, a highly selective inhibitor for CDK4/6, has been tested in numerous clinical trials and has been approved by the FDA. We previously reported that CDK inhibitors can destabilize HIF1α regardless of the presence of hypoxia and can sensitize tumor cells to TRAIL through dual blockade of CDK1 and GSK-3β. To translate this knowledge into a cancer therapeutic strategy, we investigated the therapeutic effects and molecular mechanisms of CDK inhibition against colon cancer cells under normoxia and hypoxia...
June 18, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28461660/derivation-of-mouse-embryonic-stem-es-cell-lines-using-small-molecule-inhibitors-of-erk-and-gsk3-signaling-2i
#20
Jennifer Nichols, Kenneth Jones
The efficiency of embryonic stem (ES) cell derivation is very high if embryos are incubated, from the eight-cell stage, in the presence of the two inhibitors of signaling via the Erk and Gsk3 pathways (PD0325901 and CHIR99021, respectively, known as "2i"). The success rate may vary, depending on the quality of the embryos and the speed with which they are processed, but it is not unusual to obtain ES cell lines from all embryos allocated to the study, even from the least permissive strains. Furthermore, ES cells can be efficiently obtained from any complex genetic mouse model or for in vitro analysis and additional genetic manipulation in any background of choice...
May 1, 2017: Cold Spring Harbor Protocols
keyword
keyword
115967
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"