A5003532151- Enzyme Structure and Function
- Metalloenzymes and iron-sulfur proteins
- Protein Kinase Regulation and GTPase Signaling
- Neuroblastoma Research and Treatments
- Melanoma and MAPK Pathways
- Lung Cancer Research Studies
- Microtubule and mitosis dynamics
- Lung Cancer Treatments and Mutations
- Polyoxometalates: Synthesis and Applications
- Advanced Electron Microscopy Techniques and Applications
- Porphyrin Metabolism and Disorders
- Enzyme Production and Characterization
- Microbial Metabolism and Applications
- RNA modifications and cancer
- Cancer therapeutics and mechanisms
- Metal Extraction and Bioleaching
- Peptidase Inhibition and Analysis
- RNA and protein synthesis mechanisms
- Algal biology and biofuel production
- Metal-Catalyzed Oxygenation Mechanisms
- Protein Structure and Dynamics
- Clusterin in disease pathology
Sanofi (France)
2005-2020
John Innes Centre
1999-2001
Norwich University
2001
In its apo state kinase p38 effects slow motions that can be detected in the NMR spectrum. One of affected parts is pharmacologically interesting DFG motif. Diarylurea inhibitors bind to DFG-out conformation lock this motif a defined state, whereas DFG-in adjacent hinge region leave flexibility unaffected (see crystal structure complex with inhibitor SB203580).
The Aurora family of serine/threonine kinases is essential for mitosis. Their crucial role in cell cycle regulation and aberrant expression a broad range malignancies have been demonstrated prompted intensive search small molecule inhibitors. Indeed, over 10 them reached the clinic as potential anticancer therapies. We report herein discovery optimization novel series tricyclic molecules that has led to SAR156497, an exquisitely selective A, B, C inhibitor with vitro vivo efficacy. also...
KRAS genes belong to the most frequently mutated family of oncogenes in cancer. The G12C mutation, found a third lung, half colorectal and pancreatic cancer cases, is believed be responsible for substantial number deaths. For 30 years, has been subject extensive drug-targeting efforts aimed at targeting protein itself, but also its post-translational modifications, membrane localization, protein-protein interactions downstream signalling pathways. So far, strategies have failed, there are no...
In ihrem Apozustand führt die Kinase p38 langsame Bewegungen aus, sich im NMR-Spektrum nachweisen lassen. Einer der betreffenden Molekülbereiche ist das pharmakologisch wichtige DFG-Motiv. Diarylharnstoff-Inhibitoren, an „DFG-out“-Konformation binden, frieren dieses Motiv in einem definierten Zustand ein, während „DFG-in“-Inhibitoren, benachbarte Hinge-Region Flexibilität nicht beeinflussen (siehe Kristallstruktur von Komplex mit dem Inhibitor SB203580).
Crystals of the molbindin ModG (subunit M r = 14359 Da), a cytoplasmic molybdate-binding protein from Azotobacter vinelandii , were grown by vapour diffusion. Both apo and tungstate-bound forms crystallized X-ray data collected at 100 K. Apo-ModG crystallizes in space group P 6 3 22, with unit-cell dimensions b 90.62, c 79.46 Å. Native to resolution 2.5 Å single crystal, which showed marked improvement diffraction quality after annealing. Data single-site gold derivative also 2.7 resolution....
Abstract Anaplastic lymphoma kinase (ALK) is a receptor tyrosine belonging to the insulin superfamily. Activating mutations in ALK are oncogenic and cause 10 15% of neuroblastoma cases. Similarly, activating fusions have been detected several cancers, including ALCL (NPM-ALK 70% patients) NSCLC (EML4-ALK 3–7% patients). inhibitors from different compound classes selectivity profiles currently undergoing clinical development, among which crizotinib has recently received marketing approval US...
Abstract Anaplastic lymphoma kinase (ALK) is a receptor tyrosine belonging to the insulin superfamily. Activating mutations in ALK are oncogenic and cause 10% 15% of neuroblastoma cases. Similarly, activating fusions have been detected several cancers, including ALCL (NPM-ALK 70% patients) NSCLC (EML4-ALK 3% 7% patients). Several inhibitors currently undergoing clinical development, among which crizotinib has recently received marketing approval from U.S. FDA under name Xalkori. This...
Abstract YAP1 and TEAD are transcriptional regulators involved in organ size control cell proliferation. Aberrant activation of has been reported for multiple tumor types inhibiting the interaction with its partner protein is thought to be a means targeting aberrant activity. In order identify small molecule inhibitors TEAD, we have performed fragment-based-screening looking ligands binding at interface (TEAD pocket S3). We employed three techniques fragment screening (NMR, SPR, DSF) cross...