A5049101929- Computational Drug Discovery Methods
- Synthetic Organic Chemistry Methods
- Metal complexes synthesis and properties
- Melanoma and MAPK Pathways
- Synthesis and biological activity
- Magnetism in coordination complexes
- Protein Kinase Regulation and GTPase Signaling
- Protein Degradation and Inhibitors
- Metal-Catalyzed Oxygenation Mechanisms
- Geophysical and Geoelectrical Methods
- Photochromic and Fluorescence Chemistry
- Electrokinetic Soil Remediation Techniques
- Analytical Chemistry and Chromatography
- Synthesis of Tetrazole Derivatives
- Bioactive Compounds and Antitumor Agents
- Organometallic Complex Synthesis and Catalysis
- Metalloenzymes and iron-sulfur proteins
- Photoreceptor and optogenetics research
- Asymmetric Synthesis and Catalysis
- Peroxisome Proliferator-Activated Receptors
- Metabolomics and Mass Spectrometry Studies
- Molecular spectroscopy and chirality
- Nitric Oxide and Endothelin Effects
- Eicosanoids and Hypertension Pharmacology
- Machine Learning in Materials Science
Guangzhou Institute of Geochemistry
2024
University of Chinese Academy of Sciences
2022-2024
Chinese Academy of Sciences
1992-2024
University of Gothenburg
2018-2024
State Key Laboratory of Oil and Gas Reservoir Geology and Exploitation
2024
Cancer Hospital of Chinese Academy of Medical Sciences
2022-2023
Zhejiang Cancer Hospital
2022-2023
Novartis (United States)
2015-2017
Ariadne Diagnostics (United States)
2015-2016
State Key Laboratory of Biotherapy
2013-2015
In the treatment of echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase positive (ALK+) non-small-cell lung cancer (NSCLC), secondary mutations within ALK domain have emerged as a major resistance mechanism to both first- and second-generation inhibitors. This report describes design synthesis series 2,4-diarylaminopyrimidine-based potent selective inhibitors culminating in identification investigational clinical candidate brigatinib. A unique structural...
Bruton's tyrosine kinase proteolysis-targeting chimeras (BTK-PROTACs) have emerged as a promising approach to address the limitations of BTK inhibitors. However, conducting rational discovery orally bioavailable BTK-PROTACs presents significant challenges. In this study, dimensionality reduction analysis and model molecule validation were utilized identify some key structural features for improving oral absorption BTK-PROTACs. The results applied optimize newly discovered B1 B2. Compound C13...
Lactate dehydrogenase A (LDH-A) catalyzes the interconversion of lactate and pyruvate in glycolysis pathway. Cancer cells rely heavily on instead oxidative phosphorylation to generate ATP, a phenomenon known as Warburg effect. The inhibition LDH-A by small molecules is therefore interest for potential cancer treatments. We describe identification optimization inhibitors fragment-based drug discovery. applied ligand based NMR screening identify low affinity fragments binding LDH-A....
A molecular equivalence number (meqnum) classifies a molecule with respect to class of structural features or topological shapes such as its cyclic system set functional groups. Meqnums can be used organize structures into nonoverlapping, yet highly relatable classes. We illustrate the construction some different types meqnums and present via examples methods comparing diverse chemical libraries based on meqnums. In we compare library which is random sample from MDL Drug Data Report (MDDR)...
The emergence of large chemical databases imposes a need for organizing the compounds in these databases. Mapping graph particular, and molecular equivalence class represented by labeled pseudograph general, to unique number or string facilitates high-throughput browsing, grouping, searching database. Computing this using naming adaptation Morgan algorithm, we observed classification noise which nonisomorphic graphs were mapped same number. Our extensions that algorithm greatly reduced noise.
Choline kinase α (ChoKα) is an enzyme involved in the synthesis of phospholipids and thereby plays key roles regulation cell proliferation, oncogenic transformation, human carcinogenesis. Since several inhibitors ChoKα display antiproliferative activity both cellular animal models, this novel oncogene has recently gained interest as a promising small molecule target for cancer therapy. Here we summarize our efforts to further validate explore ChoKα. Starting from weakly binding fragments,...
A set of azoheteroarenes have been synthesized with Buchwald–Hartwig coupling and microwave-assisted O2 oxidation as the key steps. Several compounds exhibit good to excellent photoswitching properties (high switching efficiency, fatigue resistance, thermal stability Z-isomer) relevant for photocontrolled applications, which pave way use in photopharmacology.
3,3-Bis(silyl) silyl enol ethers have been shown to exhibit predominantly Sakurai reactivity, rather than Mukaiyama aldol in their Lewis acid promoted reactions with acetals. Starting from a geminal bis(silyl) moiety consisting of two different groups, such as SiMe(3) and SiMe(2)Ph, the is selectively eliminated give monoprotected E- vinylsilyl diols good excellent syn-diastereoselectivity. This reaction also underpinned synthesis nematocidal oxylipid Notheia anomala, demonstrating...
Abstract In non-small cell lung cancer (NSCLC), multiple classes of activating mutations have been identified in EGFR and HER2 that vary widely their sensitivity to available tyrosine kinase inhibitors (TKIs). Erlotinib, gefitinib, afatinib are approved for use patients with the most common forms (ie, exon 19 deletions or L858R substitutions). However, no TKIs activated by any other mutation, including 20 insertions uncommon substitutions, class mutation (including insertions). As inhibition...
Utilizing structure-based drug design, a novel dihydropyridopyrimidinone series which exhibited potent Hsp90 inhibition, good pharmacokinetics upon oral administration, and an excellent pharmacokinetic/pharmacodynamic relationship in vivo was developed from commercial hit. The exploration of this led to the selection NVP-HSP990 as development candidate.
A regioselective 1,4-hydroiodination of dienyl alcohols has been developed using trimethylsilyl iodide as Lewis acid and source. range homoallylic containing a multisubstituted Z-alkene was synthesized with good to excellent configurational control. The approach applied in sequential hydroiodination/Prins cyclization afford tetrahydropyrans diastereoselectively.
An organosilane-based strategy has been used to accomplish the total synthesis of (–)-exiguolide. The key steps involve: (1) geminal bis(silyl) Prins cyclization construct A ring; (2) silicon-protected RCM reaction macrocycle; and (3) Hiyama–Denmark cross-coupling install side chain.
Abstract Influenza virus uses a unique mechanism to initiate viral transcription named cap-snatching. The PB2 subunit of the heterotrimeric RNA polymerase binds cap structure cellular pre-mRNA promote its cleavage by PA subunit. resulting 11–13 capped oligomer is used PB1 proteins. VX-787 an inhibitor influenza A cap-binding protein PB2. This clinical stage compound was shown bind minimal domain inhibit cap-snatching machinery. However, binding this molecule in context extended form has...
An all-photonic method is described, in which (i) the release of an active kinase inhibitor controlled externally with light; and (ii) fluorescence employed to report both binding its corresponding target.
An unusual [1,5]-Brook rearrangement of the lithium alkoxide geminal bis(silyl) homoallylic alcohol is described. The unique steric and electronic effects bis(silane) were found to be crucial for promoting this long-range silyl migration, as well facilitating subsequent γ/Z-selective addition allyllithium with carbonyl compounds synthesize diverse configurationally defined Z-vinylsilanes.
Communication of data and ideas within a medicinal chemistry project on global as well local level is crucial aspect in the drug design cycle. Over time frame eight years, we built optimized FOCUS, platform to produce, visualize, share information various aspects discovery such cheminformatics, analysis, structural information, design. FOCUS tightly integrated with internal services that involve-among others-data retrieval systems in-silico models provides easy access automated modeling...
The discovery of a highly potent and selective small molecule inhibitor 9 for in vitro target validation MNK1/2 kinases is described. aminopyrazine benzimidazole series was derived from an HTS hit optimized by utilization docking model, conformation analysis, binding pocket comparison against antitargets.
REarranged during Transfection (RET) is a transmembrane receptor tyrosine kinase that required for development of multiple human tissues, but which also an important contributor to cancers. RET activation through rearrangement or point mutations occurs in thyroid and lung Furthermore, wild type increasingly recognized mechanism promoting tumor growth dissemination much broader group therefore attractive therapeutic target small-molecule inhibitors. Non-invasive control signaling with light...