In vitro studies of a new synthetic thrombin inhibitor

David Green; Chung hsin Ts'ao; Nancy Reynolds; David Kahn; Helga Kohl; Isaac Cohen

doi:10.1016/0049-3848(85)90041-6

In vitro studies of a new synthetic thrombin inhibitor

David Green^*, Chung hsin Ts'ao, Nancy Reynolds, David Kahn, Helga Kohl, Isaac Cohen

^*Corresponding author for this work

Medicine, Hematology Oncology Division

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

21 Scopus citations

Abstract

(2R, 4R)4-methyl-l-[N^α-(3-methyl-1, 2, 3, 4-tetrahydro-8-quinoline-sulfonyl)-L-arginyl]-2-piperidine carboxylic acid monohydrate (MCI-9038) was found to be a potent synthetic inhibitor of thrombin. In concentrations as low as 1 μM, the thrombin time, prothrombin time, and partial thromboplastin time were more than doubled. The venom (Bothrops atrox) time was similarly prolonged. The drug also inhibited the thrombin-induced activation of factors VIII and XIII. While MCI-9038 in concentrations of 10^-4 M had no effect on platelet aggregation induced by collagen, ADP, epinephrine, and arachidonate, nanomolar concentrations inhibited thrombin-induced platelet aggregation and the release of platelet ADP. The drug also significantly inhibited the adhesion of thrombin-treated platelets to cultured bovine aortic endothelial cells. We conclude that MCI-9038 is an extremely potent inhibitor of the effects of thrombin on platelets and clotting factors.

Original language	English (US)
Pages (from-to)	145-153
Number of pages	9
Journal	Thrombosis Research
Volume	37
Issue number	1
DOIs	https://doi.org/10.1016/0049-3848(85)90041-6
State	Published - Jan 1 1985

Keywords

Anticoagulant
Heparin
Thrombin Inhibitor

ASJC Scopus subject areas

Hematology

Access to Document

10.1016/0049-3848(85)90041-6

Cite this

@article{a6b40e92e85f42b7b9dda80eb1e89018,

title = "In vitro studies of a new synthetic thrombin inhibitor",

abstract = "(2R, 4R)4-methyl-l-[Nα-(3-methyl-1, 2, 3, 4-tetrahydro-8-quinoline-sulfonyl)-L-arginyl]-2-piperidine carboxylic acid monohydrate (MCI-9038) was found to be a potent synthetic inhibitor of thrombin. In concentrations as low as 1 μM, the thrombin time, prothrombin time, and partial thromboplastin time were more than doubled. The venom (Bothrops atrox) time was similarly prolonged. The drug also inhibited the thrombin-induced activation of factors VIII and XIII. While MCI-9038 in concentrations of 10-4 M had no effect on platelet aggregation induced by collagen, ADP, epinephrine, and arachidonate, nanomolar concentrations inhibited thrombin-induced platelet aggregation and the release of platelet ADP. The drug also significantly inhibited the adhesion of thrombin-treated platelets to cultured bovine aortic endothelial cells. We conclude that MCI-9038 is an extremely potent inhibitor of the effects of thrombin on platelets and clotting factors.",

keywords = "Anticoagulant, Heparin, Thrombin Inhibitor",

author = "David Green and Ts'ao, {Chung hsin} and Nancy Reynolds and David Kahn and Helga Kohl and Isaac Cohen",

year = "1985",

month = jan,

day = "1",

doi = "10.1016/0049-3848(85)90041-6",

language = "English (US)",

volume = "37",

pages = "145--153",

journal = "Thrombosis Research",

issn = "0049-3848",

publisher = "Elsevier Ltd",

number = "1",

}

TY - JOUR

T1 - In vitro studies of a new synthetic thrombin inhibitor

AU - Green, David

AU - Ts'ao, Chung hsin

AU - Reynolds, Nancy

AU - Kahn, David

AU - Kohl, Helga

AU - Cohen, Isaac

PY - 1985/1/1

Y1 - 1985/1/1

N2 - (2R, 4R)4-methyl-l-[Nα-(3-methyl-1, 2, 3, 4-tetrahydro-8-quinoline-sulfonyl)-L-arginyl]-2-piperidine carboxylic acid monohydrate (MCI-9038) was found to be a potent synthetic inhibitor of thrombin. In concentrations as low as 1 μM, the thrombin time, prothrombin time, and partial thromboplastin time were more than doubled. The venom (Bothrops atrox) time was similarly prolonged. The drug also inhibited the thrombin-induced activation of factors VIII and XIII. While MCI-9038 in concentrations of 10-4 M had no effect on platelet aggregation induced by collagen, ADP, epinephrine, and arachidonate, nanomolar concentrations inhibited thrombin-induced platelet aggregation and the release of platelet ADP. The drug also significantly inhibited the adhesion of thrombin-treated platelets to cultured bovine aortic endothelial cells. We conclude that MCI-9038 is an extremely potent inhibitor of the effects of thrombin on platelets and clotting factors.

AB - (2R, 4R)4-methyl-l-[Nα-(3-methyl-1, 2, 3, 4-tetrahydro-8-quinoline-sulfonyl)-L-arginyl]-2-piperidine carboxylic acid monohydrate (MCI-9038) was found to be a potent synthetic inhibitor of thrombin. In concentrations as low as 1 μM, the thrombin time, prothrombin time, and partial thromboplastin time were more than doubled. The venom (Bothrops atrox) time was similarly prolonged. The drug also inhibited the thrombin-induced activation of factors VIII and XIII. While MCI-9038 in concentrations of 10-4 M had no effect on platelet aggregation induced by collagen, ADP, epinephrine, and arachidonate, nanomolar concentrations inhibited thrombin-induced platelet aggregation and the release of platelet ADP. The drug also significantly inhibited the adhesion of thrombin-treated platelets to cultured bovine aortic endothelial cells. We conclude that MCI-9038 is an extremely potent inhibitor of the effects of thrombin on platelets and clotting factors.

KW - Anticoagulant

KW - Heparin

KW - Thrombin Inhibitor

UR - http://www.scopus.com/inward/record.url?scp=0022001438&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0022001438&partnerID=8YFLogxK

U2 - 10.1016/0049-3848(85)90041-6

DO - 10.1016/0049-3848(85)90041-6

M3 - Article

C2 - 3983896

AN - SCOPUS:0022001438

SN - 0049-3848

VL - 37

SP - 145

EP - 153

JO - Thrombosis Research

JF - Thrombosis Research

IS - 1

ER -

In vitro studies of a new synthetic thrombin inhibitor

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this