Academia Sinica

National Taiwan University

The Rockefeller University

Cheng, Yih-shyun E.

Liu, Kung-cheng

Fang, Jim-min

Cheng, Ting-jen R.

Jan, Jia-tsrong

Wong, Chi-huey

Ting-Jen Rachel Cheng

Chi-Huey Wong

Pan-Chyr Yang

Che Ma

Jim-Min Fang

Rong-Jie Chein

Kuo-I Lin

Yi-An Ko

Szu-Hua Pan

Shih-Chi Wang

Hsin-Yu Liao

Chung-Yi Wu

Yih-Shyun Edmond Cheng

Wei-Chieh Cheng

Ming-Shiu Lin

Ting-Hung Rachel Chou

Alice L Yu

David D Ho

Yaoxing Huang

Shang-Cheng Hung

Wen-Bin Yang

Jia-Tsrong Jan

Ming Wei Chen

Yves Shang-Yi Hsieh

Cheng Chien

Chih-Chien Lin

Hao-Yu Wen

Ling-Wei Li

Hui-Ming Yu

Kung-Cheng Liu

Che-Hsiung Hsu

The present disclosure relates to a chimeric influenza virus hemagglutinin (HA) polypeptide, comprising one or more stem domain sequence, each having at least 60% homology with a stem domain consensus sequence of H1 subtype HA (H1 HA) and/or H5 subtype HA (H5 HA), fused with one or more globular head domain sequence, each having at least 60% homology with a globular head domain consensus sequence of H1 subtype HA (H1 HA) or H5 subtype HA (H5 HA).

Chimeric influenza vaccines

Provided herein are compounds of Formula (I). The disclosure provides new compounds, compositions, and methods for treating, delaying, and/or preventing the adverse effects of proliferative diseases, such as cancers including, for example, lung cancer, breast cancer, ovarian cancer, prostate cancer, head cancer, neck cancer, head and neck cancer, or leukemia (e.g., cancer resistant to treatment by one or more microtubule-targeting agents (e.g., cancer resistant to multiple drugs associated with P-glycoprotein (P-gp) overexpression)). Provided are methods of inhibiting polymerization of a cancer cell microtubule in a subject in need thereof or a cell, tissue, or biological sample, binding β-tubulin, inhibiting microtubule assembly and, inducing apoptosis in a cancer cell resistant to multiple drugs in a tissue, biological sample, or subject. Also provided in the present disclosure are pharmaceutical compositions, kits, and methods of using the compounds for treating any of the target diseases described herein.

Methods of using 4(1)-quinolone derivatives

The present disclosure provides compounds of Formulas (I), (II), and pharmaceutically acceptable salts thereof. The compounds described herein are useful in treating proliferative diseases, for example, cancer (e.g., lung cancer), and infectious diseases (e.g., bacterial infections).

4,9-dioxo-4,9-dihydronaphtho[2,3-B]furan-3-carboxamide derivatives and uses thereof for treating proliferative diseases and infectious diseases

Compounds of Formula (I) and methods for treating, delaying, and/or preventing the adverse effects of proliferative diseases, such as cancers including, for example, lung cancer, breast cancer, ovarian cancer, prostate cancer, head cancer, neck cancer, head and neck cancer, or leukemia (e.g., cancer resistant to treatment by one or more microtubule-targeting agents, e.g., cancer resistant to multiple drugs associated with P-glycoprotein (P-gp) overexpression). Methods of inhibiting polymerization of a cancer cell microtubule in a subject in need thereof or a cell, tissue, or biological sample, binding &#x3b2;-tubulin, inhibiting microtubule assembly and, inducing apoptosis in a cancer cell resistant to multiple drugs in a tissue, biological sample, or subject. Pharmaceutical compositions, kits, and methods of using the compounds for treating any of the target diseases described herein. 

4(1H)-quinolone derivatives and uses thereof

The present disclosure provides compounds of Formulas (I), (II), and pharmaceutically acceptable salts thereof. The compounds described herein are useful in treating proliferative diseases, for example, cancer (e.g., lung cancer), and infectious diseases (e.g., bacterial infections). 

4,9-dioxo-4,9-dihydronaphtho[2,3-b]furan-3-carboxamide derivatives and uses thereof for treating proliferative diseases and infectious diseases

Disclosed herein are substrates and/or inhibitors of endo-O-sulfatase 1 (Sulf-1). According to some embodiments, the substrates and/or inhibitors of Sulf-1 are compounds of formula (I) or (II), In formula (I) or (II), n is 2 or 3; X is methylene, O, or N; Ris &#x2014;SOM, or &#x2014;SONH; Ris Calkyl or Calkylamine; and M is a monovalent cation selected from the group consisting of lithium, sodium, potassium, and ammonium. Also encompasses herein are methods of identifying and treating a subject having or suspected of having osteoarthritis. The method includes steps of (a) mixing a urine sample of the subject with 4-methylumbelliferyl sulfate (4-MUS) and a Sulf-1 inhibitor of formula (I) or (II); (b) determining a fluorescence intensity of the mixture of the step (a); and (c) treating the subject with an analgesic, a non-steroidal anti-inflammatory drug (NSAID), or a corticosteroid when the determined fluorescence intensity of the step (b) is smaller than that of a control sample, which is a mixture of the urine sample and 4-MUS.

Compounds and methods for treating osteoarthritis

The present disclosure provides compounds of Formulas (I') and (I), and pharmaceutically acceptable salts thereof. The compounds described herein may be useful in treating and/or preventing proliferative diseases (e.g., cancer). Also provided in the present disclosure are pharmaceutical compositions, kits, and uses thereof for treating proliferative diseases. 

Purine compounds possessing anticancer activity

Novel dual-targeted, bifunctional anti-influenza drugs formed by conjugation with anti-inflammatory agents are disclosed. Exemplary drugs according to the invention include caffeic acid (CA)-bearing zanamivir (ZA) conjugates ZA-7-CA (1), ZA-7-CA-amide (7) and ZA-7-Nap (43) for simultaneous inhibition of influenza virus neuraminidase and suppression of proinflammatory cytokines. Synthetic methods for preparation of these enhanced anti-influenza conjugate drugs are provided. The synthetic bifunctional ZA conjugates act synergistically towards protection of mice lethally infected by H1N1 or H5N1 influenza viruses. The efficacy of ZA-7-CA, ZA-7-CA-amide and ZA-7-Nap conjugates is much greater than the combination therapy of ZA with anti-inflammatory agents.

Enhanced anti-influenza agents conjugated with anti-inflammatory activity

The crystal structure at 2.16 &#x212b; resolution of the full-length bacterial bifunctional transglycosylase penicillin-binding protein 1b (PBP1b) from, in complex with its inhibitor moenomycin, is provided. The atomic coordinates of the complex as well as the moenomycin binding site are provided. Three dimensional structures of amino acid residues involved in moenomycin binding and transglycosylation activity are identified. Binding site for peptidoglycan synthesis inhibitors comprising inhibitor-binding site comprises amino acid residues from at least one of transglycosylase (TG), UvrB domain 2 homolog (UB2H) and transmembrane (TM) domains of PBP1b are identified at an atomic level of resolution. Methods for rational drug design based on the atomic coordinates are provided. Methods for screening for antibiotics based on anisotropic binding assay and transglycosylase inhibitor assays are provided. Novel antibiotics based on the screening assays of the invention are disclosed.

[object Object]

Moenomycin inhibits bacterial growth by clocking the transglycosylase activity of class A penicillin-binding proteins (PBPs), which are key enzymes in bacterial cell wall synthesis. The binding affinities of moenomycin A with various truncated PBPs were compared showing that the transmembrane domain is important for moenomycin binding. Full-length class-A PBPs from 16 bacterial species were produced, and their binding activities showed a correlation with the antimicrobial activity of moenomycin againstand. Moreover, a fluorescence anisotropy-based high-throughput assay was developed and used successfully for identification of transglycosylase inhibitors.

Antibiotic compositions and related screening methods

A novel N-acetyl-5-N,4-O-carbonyl-protected dibutyl sialyl phosphate donor for sialylation of both primary and sterically hindered secondary acceptors to prepare sialosides with high yield and &#x3b1;-selectivity is disclosed. Methods for making disaccharide building blocks comprising &#x3b1;(2&#x2192;3), &#x3b1;(2&#x2192;6), &#x3b1;(2&#x2192;8), &#x3b1;(2&#x2192;8)/&#x3b1;(2&#x2192;9) alternate, and &#x3b1;(2&#x2192;9) sialosides are provided. methods for one-pot synthesis of complex sialosides are disclosed. Libraries of sialosides and methods for using the libraries for detection and receptor binding analysis of surface glycoproteins or pathogens and cancer cells are disclosed. Methods for distinguishing between hemagglutinin (HA) from various strains of influenza are provided.

Alpha-selective sialyl phosphate donors for preparation of sialosides and sialoside arrays for influenza virus detection

Compositions and methods are disclosed relating to use of fractions, polysaccharides, and oligosaccharides of. The fractions, polysaccharides, and oligosaccharides are able to effect an increase in beneficial cytokines and chemokines.

The crude extract of(PA) has anti-inflammatory effects and can inhibit AP-1 binding in vitro. The incubation with PA crude extract resulted in significant inhibition of the LPS-induced expression of IL-6, IL-12, MCP-1, and RANTES in HUVEC cells. After the crude extract was further fractionated using preparative HPLC, fraction 8, 9, 10 and 11 were identified to inhibit the AP-1 binding activity. The active component of fraction 8 is Mena 987; fraction 9 is Mena 998; fraction 10 is Mena 9102; and fraction 11 is rosmarinic acid and the synthetic rosmarinic acid analogues. Other compounds showed inhibitory activities as well. These compounds have inhibitory effects on AP-1 activity and are useful as preventive or therapeutic agent for diseases in which excessive expression or activities of AP-1 are involved.

Growing community of inventors

Taipei, Taiwan

Ting-Jen Rachel Cheng