LIVIVO - Das Suchportal für Lebenswissenschaften

switch to English language
Erweiterte Suche

Ihre letzten Suchen

  1. AU="Sung, Byungje"
  2. AU="David Pérez-Del Rey"
  3. AU="Gowran, Aoife"
  4. AU="Roberta Pastorino"
  5. AU="Ermakov, Alexander S"
  6. AU="YeYun Xin" AU="YeYun Xin"
  7. AU="Giugliani, Camila"
  8. AU=Cerrone Marina
  9. AU="Kohsar, Matin"
  10. AU="Ella Brandt"
  11. AU="Jiwei Wang"
  12. AU="Croda, Júlio Henrique Rosa"
  13. AU="Arkun, Ani"
  14. AU="Fan-tao KONG"
  15. AU="Field, R C"
  16. AU="Coombes, Brandon J"
  17. AU="Garay, Raúl O."
  18. AU="Jingfeng Xue"
  19. AU="Kelliher, Christina M"
  20. AU="Busby, Marjorie G"

Suchergebnis

Treffer 1 - 5 von insgesamt 5

Suchoptionen

  1. Artikel ; Online: N-terminal selective conjugation method widens the therapeutic window of antibody-drug conjugates by improving tolerability and stability.

    Ko, Min Ji / Song, Daehae / Kim, Juhee / Kim, Jae Yong / Eom, Jaehyun / Sung, Byungje / Son, Yong-Gyu / Kim, Young Min / Lee, Sang Hoon / You, Weon-Kyoo / Jung, Jinwon

    mAbs

    2021  Band 13, Heft 1, Seite(n) 1914885

    Abstract: Antibody-drug conjugates (ADCs) are targeted therapeutic agents that treat cancers by selective delivery of highly potent cytotoxic drugs to tumor cells via cancer-specific antibodies. However, their clinical benefit is limited by off-target toxicity and ...

    Abstract Antibody-drug conjugates (ADCs) are targeted therapeutic agents that treat cancers by selective delivery of highly potent cytotoxic drugs to tumor cells via cancer-specific antibodies. However, their clinical benefit is limited by off-target toxicity and narrow therapeutic windows. To overcome these limitations, we have applied reductive alkylation to develop a new type of ADC that has cytotoxic drugs conjugated to the N-terminal of an antibody through amine bonds introduced via reductive alkylation reactions (NTERM). To test whether the NTERM-conjugated ADCs can widen therapeutic windows, we synthesized three different ADCs by conjugating trastuzumab and monomethyl auristatin-F using three different methods, and compared their stability, efficacy, and toxicity. The NTERM-conjugated ADC was more stable
    Mesh-Begriff(e) Alkylation ; Animals ; Antineoplastic Agents, Immunological/chemistry ; Antineoplastic Agents, Immunological/pharmacokinetics ; Antineoplastic Agents, Immunological/pharmacology ; Antineoplastic Agents, Immunological/toxicity ; Breast Neoplasms/drug therapy ; Breast Neoplasms/genetics ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Cell Line, Tumor ; Drug Compounding ; Drug Stability ; Female ; Immunoconjugates/chemistry ; Immunoconjugates/pharmacokinetics ; Immunoconjugates/pharmacology ; Immunoconjugates/toxicity ; Oligopeptides/chemistry ; Oligopeptides/pharmacokinetics ; Oligopeptides/pharmacology ; Oligopeptides/toxicity ; Protein Stability ; Rats, Nude ; Rats, Sprague-Dawley ; Receptor, ErbB-2/antagonists & inhibitors ; Receptor, ErbB-2/genetics ; Receptor, ErbB-2/metabolism ; Trastuzumab/chemistry ; Trastuzumab/pharmacokinetics ; Trastuzumab/pharmacology ; Trastuzumab/toxicity ; Tumor Burden/drug effects ; Xenograft Model Antitumor Assays ; Rats
    Chemische Substanzen Antineoplastic Agents, Immunological ; Immunoconjugates ; Oligopeptides ; monomethylauristatin F ; ERBB2 protein, human (EC 2.7.10.1) ; Receptor, ErbB-2 (EC 2.7.10.1) ; Trastuzumab (P188ANX8CK)
    Sprache Englisch
    Erscheinungsdatum 2021-04-27
    Erscheinungsland United States
    Dokumenttyp Comparative Study ; Journal Article
    ZDB-ID 2537838-7
    ISSN 1942-0870 ; 1942-0870
    ISSN (online) 1942-0870
    ISSN 1942-0870
    DOI 10.1080/19420862.2021.1914885
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

    Zusatzmaterialien

    Kategorien

  2. Artikel ; Online: ABL001, a Bispecific Antibody Targeting VEGF and DLL4, with Chemotherapy, Synergistically Inhibits Tumor Progression in Xenograft Models.

    Yeom, Dong-Hoon / Lee, Yo-Seob / Ryu, Ilhwan / Lee, Sunju / Sung, Byungje / Lee, Han-Byul / Kim, Dongin / Ahn, Jin-Hyung / Ha, Eunsin / Choi, Yong-Soo / Lee, Sang Hoon / You, Weon-Kyoo

    International journal of molecular sciences

    2020  Band 22, Heft 1

    Abstract: Delta-like-ligand 4 (DLL4) is a promising target to augment the effects of VEGF inhibitors. A simultaneous blockade of VEGF/VEGFR and DLL4/Notch signaling pathways leads to more potent anti-cancer effects by synergistic anti-angiogenic mechanisms in ... ...

    Abstract Delta-like-ligand 4 (DLL4) is a promising target to augment the effects of VEGF inhibitors. A simultaneous blockade of VEGF/VEGFR and DLL4/Notch signaling pathways leads to more potent anti-cancer effects by synergistic anti-angiogenic mechanisms in xenograft models. A bispecific antibody targeting VEGF and DLL4 (ABL001/NOV1501/TR009) demonstrates more potent in vitro and in vivo biological activity compared to VEGF or DLL4 targeting monoclonal antibodies alone and is currently being evaluated in a phase 1 clinical study of heavy chemotherapy or targeted therapy pre-treated cancer patients (ClinicalTrials.gov Identifier: NCT03292783). However, the effects of a combination of ABL001 and chemotherapy on tumor vessels and tumors are not known. Hence, the effects of ABL001, with or without paclitaxel and irinotecan were evaluated in human gastric or colon cancer xenograft models. The combination treatment synergistically inhibited tumor progression compared to each monotherapy. More tumor vessel regression and apoptotic tumor cell induction were observed in tumors treated with the combination therapy, which might be due to tumor vessel normalization. Overall, these findings suggest that the combination therapy of ABL001 with paclitaxel or irinotecan would be a better clinical strategy for the treatment of cancer patients.
    Mesh-Begriff(e) Adaptor Proteins, Signal Transducing/antagonists & inhibitors ; Animals ; Antibodies, Bispecific/pharmacology ; Antibodies, Bispecific/therapeutic use ; Apoptosis/drug effects ; Calcium-Binding Proteins/antagonists & inhibitors ; Cell Line, Tumor ; Disease Models, Animal ; Disease Progression ; Dose-Response Relationship, Drug ; Drug Synergism ; Humans ; Mice ; Neovascularization, Pathologic/drug therapy ; Niacinamide/analogs & derivatives ; Niacinamide/pharmacology ; Niacinamide/therapeutic use ; Pyrazoles/pharmacology ; Pyrazoles/therapeutic use ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Xenograft Model Antitumor Assays
    Chemische Substanzen Adaptor Proteins, Signal Transducing ; Antibodies, Bispecific ; Calcium-Binding Proteins ; DLL4 protein, human ; Pyrazoles ; Vascular Endothelial Growth Factor A ; asciminib ; Niacinamide (25X51I8RD4)
    Sprache Englisch
    Erscheinungsdatum 2020-12-29
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms22010241
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

    Zusatzmaterialien

    Kategorien

  3. Artikel ; Online: Grabody B, an IGF1 receptor-based shuttle, mediates efficient delivery of biologics across the blood-brain barrier.

    Shin, Jung-Won / An, Sungwon / Kim, Dongin / Kim, Hyunjoo / Ahn, Jinhyung / Eom, Jaehyun / You, Weon-Kyoo / Yun, Hyesu / Lee, Bora / Sung, Byungje / Jung, Jinwon / Kim, Sehyun / Son, Yonggyu / Sung, Eunsil / Lee, Hanbyul / Lee, Suyeon / Song, Daehae / Pak, Youngdon / Sandhu, Jagdeep K /
    Haqqani, Arsalan S / Stanimirovic, Danica B / Yoo, Jiseon / Kim, Donghwan / Maeng, Sungho / Lee, Jeonghun / Lee, Sang Hoon

    Cell reports methods

    2022  Band 2, Heft 11, Seite(n) 100338

    Abstract: Effective delivery of therapeutics to the brain is challenging. Molecular shuttles use receptors expressed on brain endothelial cells to deliver therapeutics. Antibodies targeting transferrin receptor (TfR) have been widely developed as molecular ... ...

    Abstract Effective delivery of therapeutics to the brain is challenging. Molecular shuttles use receptors expressed on brain endothelial cells to deliver therapeutics. Antibodies targeting transferrin receptor (TfR) have been widely developed as molecular shuttles. However, the TfR-based approach raises concerns about safety and developmental burden. Here, we report insulin-like growth factor 1 receptor (IGF1R) as an ideal target for the molecular shuttle. We also describe Grabody B, an antibody against IGF1R, as a molecular shuttle. Grabody B has broad cross-species reactivity and does not interfere with IGF1R-mediated signaling. We demonstrate that administration of Grabody B-fused anti-alpha-synuclein (α-Syn) antibody induces better improvement in neuropathology and behavior in a Parkinson's disease animal model than the therapeutic antibody alone due to its superior serum pharmacokinetics and enhanced brain exposure. The results indicate that IGF1R is an ideal shuttle target and Grabody B is a safe and efficient molecular shuttle.
    Mesh-Begriff(e) Animals ; Blood-Brain Barrier/metabolism ; Biological Products/metabolism ; Endothelial Cells/metabolism ; Brain/metabolism ; Biological Transport ; Antibodies/metabolism
    Chemische Substanzen Biological Products ; Antibodies
    Sprache Englisch
    Erscheinungsdatum 2022-11-21
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2667-2375
    ISSN (online) 2667-2375
    DOI 10.1016/j.crmeth.2022.100338
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

    Zusatzmaterialien

    Kategorien

  4. Artikel: Structural basis for the selective inhibition of JNK1 by the scaffolding protein JIP1 and SP600125.

    Heo, Yong-Seok / Kim, Su-Kyoung / Seo, Chang Il / Kim, Young Kwan / Sung, Byung-Je / Lee, Hye Shin / Lee, Jae Il / Park, Sam-Yong / Kim, Jin Hwan / Hwang, Kwang Yeon / Hyun, Young-Lan / Jeon, Young Ho / Ro, Seonggu / Cho, Joong Myung / Lee, Tae Gyu / Yang, Chul-Hak

    The EMBO journal

    2004  Band 23, Heft 11, Seite(n) 2185–2195

    Abstract: The c-jun N-terminal kinase (JNK) signaling pathway is regulated by JNK-interacting protein-1 (JIP1), which is a scaffolding protein assembling the components of the JNK cascade. Overexpression of JIP1 deactivates the JNK pathway selectively by ... ...

    Abstract The c-jun N-terminal kinase (JNK) signaling pathway is regulated by JNK-interacting protein-1 (JIP1), which is a scaffolding protein assembling the components of the JNK cascade. Overexpression of JIP1 deactivates the JNK pathway selectively by cytoplasmic retention of JNK and thereby inhibits gene expression mediated by JNK, which occurs in the nucleus. Here, we report the crystal structure of human JNK1 complexed with pepJIP1, the peptide fragment of JIP1, revealing its selectivity for JNK1 over other MAPKs and the allosteric inhibition mechanism. The van der Waals contacts by the three residues (Pro157, Leu160, and Leu162) of pepJIP1 and the hydrogen bonding between Glu329 of JNK1 and Arg156 of pepJIP1 are critical for the selective binding. Binding of the peptide also induces a hinge motion between the N- and C-terminal domains of JNK1 and distorts the ATP-binding cleft, reducing the affinity of the kinase for ATP. In addition, we also determined the ternary complex structure of pepJIP1-bound JNK1 complexed with SP600125, an ATP-competitive inhibitor of JNK, providing the basis for the JNK specificity of the compound.
    Mesh-Begriff(e) Adaptor Proteins, Signal Transducing/chemistry ; Adaptor Proteins, Signal Transducing/metabolism ; Adenosine Triphosphate/metabolism ; Allosteric Regulation ; Anthracenes/metabolism ; Arginine/chemistry ; Binding Sites ; Blotting, Western ; Calorimetry ; Crystallography, X-Ray ; Glutamic Acid/chemistry ; HeLa Cells ; Humans ; Hydrogen Bonding ; Leucine/chemistry ; Mitogen-Activated Protein Kinase 8/antagonists & inhibitors ; Mitogen-Activated Protein Kinase 8/chemistry ; Models, Molecular ; Proline/chemistry ; Protein Binding ; Protein Conformation ; Protein Structure, Tertiary ; Signal Transduction ; Transfection
    Chemische Substanzen Adaptor Proteins, Signal Transducing ; Anthracenes ; MAPK8IP1 protein, human ; pyrazolanthrone (1TW30Y2766) ; Glutamic Acid (3KX376GY7L) ; Adenosine Triphosphate (8L70Q75FXE) ; Arginine (94ZLA3W45F) ; Proline (9DLQ4CIU6V) ; Mitogen-Activated Protein Kinase 8 (EC 2.7.11.24) ; Leucine (GMW67QNF9C)
    Sprache Englisch
    Erscheinungsdatum 2004-06-02
    Erscheinungsland England
    Dokumenttyp Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 586044-1
    ISSN 1460-2075 ; 0261-4189
    ISSN (online) 1460-2075
    ISSN 0261-4189
    DOI 10.1038/sj.emboj.7600212
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

    Zusatzmaterialien

    Kategorien

  5. Artikel ; Online: Structure of the catalytic domain of human phosphodiesterase 5 with bound drug molecules.

    Sung, Byung-Je / Hwang, Kwang Yeon / Jeon, Young Ho / Lee, J I / Heo, Yong-Seok / Kim, Jin Hwan / Moon, Jinho / Yoon, Jung Min / Hyun, Young-Lan / Kim, Eunmi / Eum, Sung Jin / Park, Sam-Yong / Lee, Jie-Oh / Lee, Tae Gyu / Ro, Seonggu / Cho, Joong Myung

    Nature

    2003  Band 425, Heft 6953, Seite(n) 98–102

    Abstract: Phosphodiesterases (PDEs) are a superfamily of enzymes that degrade the intracellular second messengers cyclic AMP and cyclic GMP. As essential regulators of cyclic nucleotide signalling with diverse physiological functions, PDEs are drug targets for the ...

    Abstract Phosphodiesterases (PDEs) are a superfamily of enzymes that degrade the intracellular second messengers cyclic AMP and cyclic GMP. As essential regulators of cyclic nucleotide signalling with diverse physiological functions, PDEs are drug targets for the treatment of various diseases, including heart failure, depression, asthma, inflammation and erectile dysfunction. Of the 12 PDE gene families, cGMP-specific PDE5 carries out the principal cGMP-hydrolysing activity in human corpus cavernosum tissue. It is well known as the target of sildenafil citrate (Viagra) and other similar drugs for the treatment of erectile dysfunction. Despite the pressing need to develop selective PDE inhibitors as therapeutic drugs, only the cAMP-specific PDE4 structures are currently available. Here we present the three-dimensional structures of the catalytic domain (residues 537-860) of human PDE5 complexed with the three drug molecules sildenafil, tadalafil (Cialis) and vardenafil (Levitra). These structures will provide opportunities to design potent and selective PDE inhibitors with improved pharmacological profiles.
    Mesh-Begriff(e) 3',5'-Cyclic-GMP Phosphodiesterases ; Binding Sites ; Carbolines/chemistry ; Carbolines/metabolism ; Catalytic Domain ; Cyclic Nucleotide Phosphodiesterases, Type 5 ; Humans ; Hydrogen Bonding ; Imidazoles/chemistry ; Imidazoles/metabolism ; Models, Molecular ; Phosphoric Diester Hydrolases/chemistry ; Phosphoric Diester Hydrolases/metabolism ; Piperazines/chemistry ; Piperazines/metabolism ; Protein Conformation ; Purines ; Sildenafil Citrate ; Sulfones ; Tadalafil ; Triazines ; Vardenafil Dihydrochloride
    Chemische Substanzen Carbolines ; Imidazoles ; Piperazines ; Purines ; Sulfones ; Triazines ; Vardenafil Dihydrochloride (5O8R96XMH7) ; Tadalafil (742SXX0ICT) ; Sildenafil Citrate (BW9B0ZE037) ; Phosphoric Diester Hydrolases (EC 3.1.4.-) ; 3',5'-Cyclic-GMP Phosphodiesterases (EC 3.1.4.35) ; Cyclic Nucleotide Phosphodiesterases, Type 5 (EC 3.1.4.35) ; PDE5A protein, human (EC 3.1.4.35)
    Sprache Englisch
    Erscheinungsdatum 2003-09-04
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/nature01914
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

    Zusatzmaterialien

    Kategorien

Zum Seitenanfang