Kaixian Chen

Bio: Kaixian Chen is an academic researcher from Chinese Academy of Sciences. The author has contributed to research in topics: Virtual screening & Docking (molecular). The author has an hindex of 47, co-authored 380 publications receiving 9209 citations. Previous affiliations of Kaixian Chen include Shanghai University & East China University of Science and Technology.

불소로 치환된 시클로프로필아민계 화합물 및 이의 제조 방법, 약물 조성물 및 용도

Abstract: 본 발명은 약물 화학 및 약물 치료 분야에 관한 것으로, 구체적으로 일반식I의 화합물, 이의 라세미체, R-이성질체, S-이성질체, 약용 가능한 염 및 이들의 혼합물, 이의 제조 방법, 이러한 화합물을 함유한 약물 조성물 및 라이신 특이적 디메틸라아제-1(LSD1) 억제제로서의 용도에 관한 것이다. 암증 치료에서의 본 발명에 관한 불소로 치환된 시클로프로필아민계의 용도에 관한 것이다.일반식I

Density Functional Theory (DFT) Study on the Interaction of Ammonium (NH4+) and Aromatic Nitrogen Heterocyclics

Abstract: A DFT calculation was performed at the B3LYP/6-31G* level on the complexes formed by NH4+ and aromatic nitrogen heterocyclics, viz. pyrrole, imidazole, pyridine and indole, in order to investigate the mechanism and complexity of the interaction between the ammonium group and the aromatic heterocyclic in biomacromolecules. The optimized geometries suggested that there are two different types of complexes: one is a cation–π complex and the other is a hydrogen bond complex. A cation–π complex will be formed if the heteroatom has no localized lone-pair electrons. A hydrogen bond complex will be formed by proton transfer from NH4+ to the heteroatom if the heteroatom has localized lone-pair electrons. In the case of the cation–π complex, the predicted geometries, atomic charges and thermodynamic parameters revealed that ammonium binds more strongly to heterocyclics than it binds to benzene. The calculated orbital coefficient and the optimized structures implied that NH4+ interacts with the π electrons of the CC bond of heterocyclics to form a cation–π complex mainly through one hydrogen atom. Regarding the hydrogen bond complex, although the calculated binding strength is similar to that for the cation–π complex, the ΔH of the whole reaction process suggested that the formation of the hydrogen bond complex is favorable to the stability of the whole system. Calculated IR spectra showed that three groups of new bands appear when NH4+ binds to heterocyclics. Normal mode analysis showed that these new bands are all related to the relative motion of the two parts in the formed complexes. All these results suggest that the NH4+–heterocyclic system is a better model for studying the nature and complexity of the interaction between the ammonium group and the aromatic ring structure in biomolecules.

Cyclization strategy leads to highly potent Bromodomain and extra-terminal (BET) Bromodomain inhibitors for the treatment of acute liver injury.

Abstract: Acute liver injury (ALI) is characteristic of abrupt hepatic dysfunction and inflammatory response, and currently the main treatment for ALI is merely supportive rather than curative. Therefore, the development of novel and effective therapeutic strategies for ALI therapy is highly desirable. The emerging biological understanding of the role of BET Bromodomains has opened up an exciting opportunity to develop potent BET Bromodomain inhibitors as an effective therapeutic strategy for the treatment of acute liver injury. Herein, we synthesized a series of potent BET Bromodomain inhibitors with a tetracyclic scaffold, exemplified by compound 28 which showed good in vitro anti-inflammatory activity and good therapeutic effects in the LPS-induced acute liver injury model without obvious cytotoxicity, suggesting that compound 28 is a highly promising candidate worthy for further development.

Hexahydrodibenzo[a,g]quinolizine compound, manufacturing method therefor, pharmaceutical composition and application thereof

Abstract: PROBLEM TO BE SOLVED: To provide a novel hexahydrodibenzo[a,g]quinolizine compound having strong effect for treating diseases such as neurological diseases related to a dopamine receptor and a serotonin receptor, especially Parkinson disease, schizophrenia, drug dependence and migraine.SOLUTION: There are provided a novel hexahydrodibenzo[a,g]quinolizine compound represented by the general formula (I) and a derivative thereof, enantiomers thereof, diastereomers, racemic bodies and a mixture thereof and a pharmaceutically acceptable salt thereof.SELECTED DRAWING: None

Quantum Chemical HF/4-31G Calculations on Buckminsterfullerene Intermediates.

Abstract: Quantum chemical ab initio (U)HF/4-31G investigation on buckminsterfullerene and some proposed intermediates in its formation is carried out in this study with a view to better understanding how small carbon species carry out self-assembly to form fullerenes. The calculations on 19 carefully designed fullerene intermediates reveal that the core of an intermediate, rather than the number of its dangling bonds or abutting pentagon rings, has an intrinsic effect on its energy. The computational results show that hexagonal-core structures have lower energies than pentagonal-core structures. In addition, the pentagonal core enclosed completely by hexagonal rings has the highest energy. The UHF/4-31G results also suggest that some intermediates such as C18, C21 and C30 with hexagonal cores have unusually low energies in comparison with their isomers or neighbours. Based on these calculated results, we outline the possible pathways from precursor to intermediates to fullerenes, subject to synthesis conditions and raw materials. These pathways support some existing proposals, such as medium monocyclic ring stacking and small ring polymerization mechanisms. However, our results do not suggest that the numbers of dangling bonds or abutting pentagonal rings have the highest impact on fullerene formation. The calculated thermodynamic parameters of the dimerization and addition reactions between two bowl-shaped intermediates suggest that these reactions are favorable to fullerene formation, and that the concentration of bowl-shaped fullerene intermediates should be very low in all detectable carbon species.

Pattern Recognition and Machine Learning

Abstract: Probability Distributions.- Linear Models for Regression.- Linear Models for Classification.- Neural Networks.- Kernel Methods.- Sparse Kernel Machines.- Graphical Models.- Mixture Models and EM.- Approximate Inference.- Sampling Methods.- Continuous Latent Variables.- Sequential Data.- Combining Models.

“Bioinformatics” 특집을 내면서

Abstract: BIOE 402. Medical Technology Assessment. 2 or 3 hours. Bioentrepreneur course. Assessment of medical technology in the context of commercialization. Objectives, competition, market share, funding, pricing, manufacturing, growth, and intellectual property; many issues unique to biomedical products. Course Information: 2 undergraduate hours. 3 graduate hours. Prerequisite(s): Junior standing or above and consent of the instructor.

Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors

Abstract: A new coronavirus, known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the aetiological agent responsible for the 2019–2020 viral pneumonia outbreak of coronavirus disease 2019 (COVID-19)1–4. Currently, there are no targeted therapeutic agents for the treatment of this disease, and effective treatment options remain very limited. Here we describe the results of a programme that aimed to rapidly discover lead compounds for clinical use, by combining structure-assisted drug design, virtual drug screening and high-throughput screening. This programme focused on identifying drug leads that target main protease (Mpro) of SARS-CoV-2: Mpro is a key enzyme of coronaviruses and has a pivotal role in mediating viral replication and transcription, making it an attractive drug target for SARS-CoV-25,6. We identified a mechanism-based inhibitor (N3) by computer-aided drug design, and then determined the crystal structure of Mpro of SARS-CoV-2 in complex with this compound. Through a combination of structure-based virtual and high-throughput screening, we assayed more than 10,000 compounds—including approved drugs, drug candidates in clinical trials and other pharmacologically active compounds—as inhibitors of Mpro. Six of these compounds inhibited Mpro, showing half-maximal inhibitory concentration values that ranged from 0.67 to 21.4 μM. One of these compounds (ebselen) also exhibited promising antiviral activity in cell-based assays. Our results demonstrate the efficacy of our screening strategy, which can lead to the rapid discovery of drug leads with clinical potential in response to new infectious diseases for which no specific drugs or vaccines are available. A programme of structure-assisted drug design and high-throughput screening identifies six compounds that inhibit the main protease of SARS-CoV-2, demonstrating the ability of this strategy to isolate drug leads with clinical potential.

New Substructure Filters for Removal of Pan Assay Interference Compounds (PAINS) from Screening Libraries and for Their Exclusion in Bioassays

Abstract: This report describes a number of substructural features which can help to identify compounds that appear as frequent hitters (promiscuous compounds) in many biochemical high throughput screens. The compounds identified by such substructural features are not recognized by filters commonly used to identify reactive compounds. Even though these substructural features were identified using only one assay detection technology, such compounds have been reported to be active from many different assays. In fact, these compounds are increasingly prevalent in the literature as potential starting points for further exploration, whereas they may not be.