A5022986288- Protein Degradation and Inhibitors
- Multiple Myeloma Research and Treatments
- TGF-β signaling in diseases
- Cancer, Hypoxia, and Metabolism
- Cancer, Stress, Anesthesia, and Immune Response
- Histone Deacetylase Inhibitors Research
- RNA Interference and Gene Delivery
- Cancer Immunotherapy and Biomarkers
- Advanced biosensing and bioanalysis techniques
- Inflammatory mediators and NSAID effects
- Protein Kinase Regulation and GTPase Signaling
- Cancer-related gene regulation
- Liver Disease Diagnosis and Treatment
- Attention Deficit Hyperactivity Disorder
- Liver physiology and pathology
- Psychedelics and Drug Studies
- Nail Diseases and Treatments
- Hepatocellular Carcinoma Treatment and Prognosis
- Sarcoma Diagnosis and Treatment
- HIV Research and Treatment
- Pharmacological Effects and Toxicity Studies
- Microscopic Colitis
- Bone Metabolism and Diseases
- Pharmaceutical studies and practices
- Genetic factors in colorectal cancer
GlaxoSmithKline (France)
2009-2021
GlaxoSmithKline (United Kingdom)
2004-2014
Molecular Discovery (United Kingdom)
2014
Optimization of the screening hit 1 led to identification novel 1,5-naphthyridine aminothiazole and pyrazole derivatives, which are potent selective inhibitors transforming growth factor-β type I receptor, ALK5. Compounds 15 19, inhibited ALK5 autophosphorylation with IC50 = 6 4 nM, respectively, showed activities in both binding cellular assays exhibited selectivity over p38 mitogen-activated protein kinase. The X-ray crystal structure 19 complex human is described, confirming mode proposed...
Through their function as epigenetic readers of the histone code, BET family bromodomain-containing proteins regulate expression multiple genes therapeutic relevance, including those involved in tumor cell growth and inflammation. bromodomain inhibitors have profound antiproliferative anti-inflammatory effects which translate into efficacy oncology inflammation models, first compounds now progressed clinical trials. The exciting biology BETs has led to great interest discovery novel...
1 Chronic liver disease is characterized by an exacerbated accumulation of matrix, causing progressive fibrosis, which may lead to cirrhosis. Transforming growth factor beta (TGF-beta), a well-known profibrotic cytokine, transduces its signal through the ALK5 ser/thr kinase receptor, and increases transcription different genes including PAI-1 collagens. The identification GW6604 (2-phenyl-4-(3-pyridin-2-yl-1H-pyrazol-4-yl)pyridine), inhibitor, allowed us evaluate therapeutic potential...
Bromodomains (BRDs) are small protein domains found in a variety of proteins that recognize and bind to acetylated histone tails. This binding affects chromatin structure facilitates the localisation transcriptional complexes specific genes, thereby regulating epigenetically controlled processes including gene transcription mRNA elongation. Inhibitors bromodomain extra-terminal (BET) BRD2-4 T, which prevent acetyl-modified tails, have shown therapeutic promise several diseases. We report...
Abstract Immunotherapies prime or activate patient’s immune system to fight disease and has recently been a source of registered promising new cancer treatments with major beneficial clinical outcomes in several cancers. However, by increasing the activity system, therapies as such targeting checkpoint blockade can have profound inflammatory side effects, termed immune-related adverse events, particular organs affected gastrointestinal tract, endocrine glands, skin liver. In patients treated...
Immunotherapies prime or activate patient's immune system to fight disease and has recently been a source of registered promising new cancer treatments with major beneficial clinical outcomes in several cancers. However, by increasing the activity system, therapies as such targeting checkpoint blockade can have profound inflammatory side effects, termed immune-related adverse events, particular organs affected gastrointestinal tract, endocrine glands, skin liver. In patients treated...
Abstract Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death and accounts for >80% primary liver cancer worldwide. Early stage HCC can be treated by local ablation, surgical resection or transplantation. Systemic pharmacological options are limited only a few available (kinase immune-checkpoint inhibitors). Most cases occur in setting chronic diseases. Risk factors include Hepatitis B C, alcohol addiction metabolic multistep process comprising injury,...
Abstract Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death and accounts for over 80% primary liver cancer worldwide. Early stage HCC can be treated by local ablation, surgical resection or transplantation. Systemic pharmacological options are limited (kinase immune-checkpoint inhibitors). Most cases occur in setting chronic diseases. Risk factors include Hepatitis B C, alcohol addiction metabolic a multistep process comprising injury, inflammation,...