Design and identification of selective HER-2 sheddase inhibitors via P1' manipulation and unconventional P2' perturbations to induce a molecular metamorphosis.

Design and identification of selective HER-2 sheddase inhibitors via P1' manipulation and unconventional P2' perturbations to induce a molecular metamorphosis. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Design and identification of selective HER-2 sheddase inhibitors via P1' manipulation and unconventional P2' perturbations to induce a molecular metamorphosis. Abstract Text:

Wenqing Yao,Jincong Zhuo,David M Burns,Yun-Long Li,Ding-Quan Qian,Colin Zhang,Chunhong He,Meizhong Xu,Eric Shi,Yanlong Li,Cindy A Marando,Maryanne B Covington,Gengjie Yang,Xiangdong Liu,Max Pan,Jordan S Fridman,Peggy Scherle,Zelda R Wasserman,Gregory Hollis,Kris Vaddi,Swamy Yeleswaram,Robert Newton,Steve Friedman,Brian Metcalf,Wenqing Yao,Jincong Zhuo,David M Burns,Yun-Long Li,Ding-Quan Qian,Colin Zhang,Chunhong He,Meizhong Xu,Eric Shi,Yanlong Li,Cindy A Marando,Maryanne B Covington,Gengjie Yang,Xiangdong Liu,Max Pan,Jordan S Fridman,Peggy Scherle,Zelda R Wasserman,Gregory Hollis,Kris Vaddi,Swamy Yeleswaram,Robert Newton,Steve Friedman,Brian Metcalf,

In an effort to obtain a MMP selective and potent inhibitor of HER-2 sheddase (ADAM-10), the P1' group of a novel class of (6S,7S)-7-[(hydroxyamino)carbonyl]-6-carboxamide-5-azaspiro[2.5]octane-5-carboxylates was attenuated and the structure-activity relationships (SAR) will be discussed. In addition, it was discovered that unconventional perturbation of the P2' moiety could confer MMP selectivity, which was hypothesized to be a manifestation of the P2' group effecting global conformational changes.

Design and identification of selective HER-2 sheddase inhibitors via P1' manipulation and unconventional P2' perturbations to induce a molecular metamorphosis. Publishing Authors By Initials

W Yao,J Zhuo,DM Burns,YL Li,DQ Qian,C Zhang,C He,M Xu,E Shi,Y Li,CA Marando,MB Covington,G Yang,X Liu,M Pan,JS Fridman,P Scherle,ZR Wasserman,G Hollis,K Vaddi,S Yeleswaram,R Newton,S Friedman,B Metcalf,W Yao,J Zhuo,DM Burns,YL Li,DQ Qian,C Zhang,C He,M Xu,E Shi,Y Li,CA Marando,MB Covington,G Yang,X Liu,M Pan,JS Fridman,P Scherle,ZR Wasserman,G Hollis,K Vaddi,S Yeleswaram,R Newton,S Friedman,B Metcalf,

For similar abstracts research abstracts see: abstracts research

PUBMED ID PMID:

MEDLINE DATE:

Design and identification of selective HER-2 sheddase inhibitors via P1' manipulation and unconventional P2' perturbations to induce a molecular metamorphosis. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Bioorganic & medicinal chemistry letters

VOLUME: 18

Page Numbers: 159-63

Journal Abbreviation: Bioorg. Med. Chem. Lett.

ISSN: 1464-3405

DAY: 4

MONTH: 11

YEAR: 2007

Design and identification of selective HER-2 sheddase inhibitors via P1' manipulation and unconventional P2' perturbations to induce a molecular metamorphosis. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9107377

Design and identification of selective HER-2 sheddase inhibitors via P1' manipulation and unconventional P2' perturbations to induce a molecular metamorphosis. Keywords Mesh Terms:

KEYWORDS:

MESH TERMS:

Chemical & Substance for Abstract: Design and identification of selective HER-2 sheddase inhibitors via P1' manipulation and unconventional P2' perturbations to induce a molecular metamorphosis. Information

Substance Name:

Registry Number:

Grant and Affiliation Information for Design and identification of selective HER-2 sheddase inhibitors via P1' manipulation and unconventional P2' perturbations to induce a molecular metamorphosis.

AFFILIATION: Incyte Corporation, Department of Medicinal Chemistry, Wilmington, DE 19880, USA. wyao@incyte.com

Country: England

AGENCY:

GRANT:

ACRONYM:

MEDLINETA: Bioorg Med Chem Lett

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Design and identification of selective HER-2 sheddase inhibitors via P1' manipulation and unconventional P2' perturbations to induce a molecular metamorphosis Related Publications

• A thymus responsive phase in leukaemogenesis in AKR mice.
• An appraisal of tumor-virus problems.
• Blood determination and estimation of blood loss during surgical operations.
• Carcinoma of the pinna.
• Circulating natriuretic peptides in cats with heart disease.
• Concise review: hematopoietic stem cells and tissue stem cells: current concepts and unanswered questions.
• Crystallization and preliminary diffraction studies of the C-terminal domain of the DipZ homologue from Mycobacterium tuberculosis.
• Design and identification of selective HER-2 sheddase inhibitors via P1' manipulation and unconventional P2' perturbations to induce a molecular metamorphosis.
• Enlarging scalp nodule. Proliferating trichilemmal cyst (PTC).
• Genetic analysis of the methanol- and methylamine-specific methyltransferase 2 genes of Methanosarcina acetivorans C2A.
• Genetic and proteomic analyses of CO utilization by Methanosarcina acetivorans.
• HOST-CELL REPOPULATION OF NORMAL SPLEEN GRAFTS.
• Hematopoietic cytokines.
• Hemopoietic colonies: in vitro cloning of normal and leukemic cells.
• High-resolution sonography of acute appendicitis.
• Home-built Nd:YAG laser for general laboratory use.
• Human lung innate immune response to Bacillus anthracis spore infection.
• Interferometric measurement of acoustic velocity in PbMoO4 and TeO2.
• Mesalazine: an overview of key preclinical studies.
• Microbial metabolism of reduced phosphorus compounds.
• Mutagenesis of the C1 Oxidation Pathway in Methanosarcina barkeri: New Insights into the Mtr/Mer Bypass Pathway.
• Negative Selection on BRCA1 Susceptibility Alleles Sheds Light on the Population Genetics of Late-Onset Diseases and Aging Theory.
• Nonobstructive lateral portal vein-vena cava anastomosis; a clinical application of the Smith Freeman clamp.
• OP17.02: Use of ultrasound to reduce the need for hysteroscopy in the management of postmenopausal bleeding (PMB): introduction of a 'one-stop' clinic.
• Report of a case of postvaccinal encephalitis in a 4-month-old child with recovery.
• Sources and biology of regulatory factors active on mouse myeloid leukemic cells.
• Synchronous cavity mode and feedback wavelength scanning in dye laser oscillators with gratings.
• The origin of mitotic cells in normal thymus grafts.
• Unusual transformations in the biosynthesis of the antibiotic phosphinothricin tripeptide.
• Zener double exchange from local valence fluctuations in magnetite.