Novel quinazoline endothelin converting enzyme inhibitors

Kyunghye Ahn; Andre M. Sisneros; Sharon Pan; Donald Hupe; Sham Ni Kam; Chitase Lee; Annette Doherty; Semiko Kaw; Noriaki Emoto; Masashi Yanagisawa

Novel quinazoline endothelin converting enzyme inhibitors

Kyunghye Ahn, Andre M. Sisneros, Sharon Pan, Donald Hupe, Sham Ni Kam, Chitase Lee, Annette Doherty, Semiko Kaw, Noriaki Emoto, Masashi Yanagisawa

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

PD 069185 is a highly selective and structurally novel inhibitor of endothelin converting enzyme-1 (ECE-1). PD 069185 is a trisubstituted quinazoline and has an IC50 value of 0.9 /iM for human ECE-1 inhibition. Kinetic analysis revealed that PD 069185 is a competitive inhibitor with a Ki value of 1.1 /iM and act in a reversible fast-binding manner. The closely related enzyme, ECE2, is not inhibited at up to 100 M PD 069185. In addition, PD 069185 at 100 fiM has no effect on other metalloproteases, such as neutral endopeptidase 24.11 and stromelysin, showing a high ECE-1 specificity. Selected analogs in this series will be profiled. This non-peptide ECE-1 inhibitor should serve as a valuable tool to study the pathophysiological role of endothelin and the therapeutic potential of ECE-1 inhibitors.

Original language	English (US)
Pages (from-to)	A1404
Journal	FASEB Journal
Volume	10
Issue number	6
State	Published - Dec 1 1996

ASJC Scopus subject areas

Biotechnology
Biochemistry
Molecular Biology
Genetics

Cite this

@article{9e00083b6a594a5792b90629e0088eb2,

title = "Novel quinazoline endothelin converting enzyme inhibitors",

abstract = "PD 069185 is a highly selective and structurally novel inhibitor of endothelin converting enzyme-1 (ECE-1). PD 069185 is a trisubstituted quinazoline and has an IC50 value of 0.9 /iM for human ECE-1 inhibition. Kinetic analysis revealed that PD 069185 is a competitive inhibitor with a Ki value of 1.1 /iM and act in a reversible fast-binding manner. The closely related enzyme, ECE2, is not inhibited at up to 100 M PD 069185. In addition, PD 069185 at 100 fiM has no effect on other metalloproteases, such as neutral endopeptidase 24.11 and stromelysin, showing a high ECE-1 specificity. Selected analogs in this series will be profiled. This non-peptide ECE-1 inhibitor should serve as a valuable tool to study the pathophysiological role of endothelin and the therapeutic potential of ECE-1 inhibitors.",

author = "Kyunghye Ahn and Sisneros, {Andre M.} and Sharon Pan and Donald Hupe and Kam, {Sham Ni} and Chitase Lee and Annette Doherty and Semiko Kaw and Noriaki Emoto and Masashi Yanagisawa",

year = "1996",

month = dec,

day = "1",

language = "English (US)",

volume = "10",

pages = "A1404",

journal = "FASEB Journal",

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T1 - Novel quinazoline endothelin converting enzyme inhibitors

AU - Ahn, Kyunghye

AU - Sisneros, Andre M.

AU - Pan, Sharon

AU - Hupe, Donald

AU - Kam, Sham Ni

AU - Lee, Chitase

AU - Doherty, Annette

AU - Kaw, Semiko

AU - Emoto, Noriaki

AU - Yanagisawa, Masashi

PY - 1996/12/1

Y1 - 1996/12/1

N2 - PD 069185 is a highly selective and structurally novel inhibitor of endothelin converting enzyme-1 (ECE-1). PD 069185 is a trisubstituted quinazoline and has an IC50 value of 0.9 /iM for human ECE-1 inhibition. Kinetic analysis revealed that PD 069185 is a competitive inhibitor with a Ki value of 1.1 /iM and act in a reversible fast-binding manner. The closely related enzyme, ECE2, is not inhibited at up to 100 M PD 069185. In addition, PD 069185 at 100 fiM has no effect on other metalloproteases, such as neutral endopeptidase 24.11 and stromelysin, showing a high ECE-1 specificity. Selected analogs in this series will be profiled. This non-peptide ECE-1 inhibitor should serve as a valuable tool to study the pathophysiological role of endothelin and the therapeutic potential of ECE-1 inhibitors.

AB - PD 069185 is a highly selective and structurally novel inhibitor of endothelin converting enzyme-1 (ECE-1). PD 069185 is a trisubstituted quinazoline and has an IC50 value of 0.9 /iM for human ECE-1 inhibition. Kinetic analysis revealed that PD 069185 is a competitive inhibitor with a Ki value of 1.1 /iM and act in a reversible fast-binding manner. The closely related enzyme, ECE2, is not inhibited at up to 100 M PD 069185. In addition, PD 069185 at 100 fiM has no effect on other metalloproteases, such as neutral endopeptidase 24.11 and stromelysin, showing a high ECE-1 specificity. Selected analogs in this series will be profiled. This non-peptide ECE-1 inhibitor should serve as a valuable tool to study the pathophysiological role of endothelin and the therapeutic potential of ECE-1 inhibitors.

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M3 - Article

AN - SCOPUS:9844244238

SN - 0892-6638

VL - 10

SP - A1404

JO - FASEB Journal

JF - FASEB Journal

IS - 6

ER -

Novel quinazoline endothelin converting enzyme inhibitors

Abstract

ASJC Scopus subject areas

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