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  Synthesis and biological evaluation of aeroplysinin analogues: A new class of receptor tyrosine kinase inhibitors

Hinterding, K., Knebel, A., Herrlich, P., & Waldmann, H. (1998). Synthesis and biological evaluation of aeroplysinin analogues: A new class of receptor tyrosine kinase inhibitors. BIOORGANIC & MEDICINAL CHEMISTRY, 6(8), 1153-1162. doi:10.1016/S0968-0896(98)00070-4.

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 Creators:
Hinterding, K1, Author
Knebel, A1, Author
Herrlich, P1, Author
Waldmann, Herbert2, Author           
Affiliations:
1external, ou_persistent22              
2Abt. IV: Chemische Biologie, Max Planck Institute of Molecular Physiology, Max Planck Society, ou_1753290              

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Free keywords: GROWTH-FACTOR-RECEPTOR; SIGNAL-TRANSDUCTION; PROTEIN-KINASE; SELECTIVE-INHIBITION; POTENT; PHOSPHORYLATION; ACTIVATION; QUINONES; AGENTS; CELLS Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry; tyrosine kinase; enzyme inhibition; aeroplysinin; EGF receptor; PDGF receptor;
 Abstract: Receptor tyrosine kinases (RTKs), such as the epidermal growth factor receptor (EGFR) and the platelet-derived growth factor receptor (PDGFR), are critically involved in the transduction of mitogenic signals across the plasma membrane and therefore in the regulation of cell growth and proliferation. Enhanced RTK activity is associated with proliferative diseases such as cancer, psoriasis and atherosclerosis, while decreased function may be associated for instance with diabetes. EGFR and PDGFR are selectively inhibited by analogues of the marine natural product aeroplysinin. The synthetic inhibitors display IC50 values in the low micromolar range and in contrast to the natural product show pronounced inhibitory activity in cultured cells in vivo. The mechanism of inhibition is likely based on a covalent modification of the target enzymes by reaction of epoxy ketone 8 with various nucleophiles. (C) 1998 Elsevier Science Ltd. All rights reserved.

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Language(s): eng - English
 Dates: 1998-08
 Publication Status: Issued
 Pages: 10
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Degree: -

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Title: BIOORGANIC & MEDICINAL CHEMISTRY
Source Genre: Journal
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Publ. Info: KIDLINGTON, OXFORD : PERGAMON-ELSEVIER SCIENCE
Pages: - Volume / Issue: 6 (8) Sequence Number: - Start / End Page: 1153 - 1162 Identifier: ISSN: 0968-0896