Chemical Adjustment of Fibrinolysis

Fibrinolysis is the process of the fibrin–platelet clot dissolution initiated after bleeding has been stopped. It is regulated by a cascade of proteolytic enzymes with plasmin at its core. In pathological cases, the balance of normal clot formation and dissolution is replaced by a too rapid lysis, l...

Full description

Bibliographic Details
Main Authors: Alexey M. Shibeko, Ivan S. Ilin, Nadezhda A. Podoplelova, Vladimir B. Sulimov, Mikhail A. Panteleev
Format: Article
Language:English
Published: MDPI AG 2024-01-01
Series:Pharmaceuticals
Subjects:
Online Access:https://www.mdpi.com/1424-8247/17/1/92
_version_ 1797342819858251776
author Alexey M. Shibeko
Ivan S. Ilin
Nadezhda A. Podoplelova
Vladimir B. Sulimov
Mikhail A. Panteleev
author_facet Alexey M. Shibeko
Ivan S. Ilin
Nadezhda A. Podoplelova
Vladimir B. Sulimov
Mikhail A. Panteleev
author_sort Alexey M. Shibeko
collection DOAJ
description Fibrinolysis is the process of the fibrin–platelet clot dissolution initiated after bleeding has been stopped. It is regulated by a cascade of proteolytic enzymes with plasmin at its core. In pathological cases, the balance of normal clot formation and dissolution is replaced by a too rapid lysis, leading to bleeding, or an insufficient one, leading to an increased thrombotic risk. The only approved therapy for emergency thrombus lysis in ischemic stroke is recombinant tissue plasminogen activator, though streptokinase or urokinase-type plasminogen activators could be used for other conditions. Low molecular weight compounds are of great interest for long-term correction of fibrinolysis dysfunctions. Their areas of application might go beyond the hematology field because the regulation of fibrinolysis could be important in many conditions, such as fibrosis. They enhance or weaken fibrinolysis without significant effects on other components of hemostasis. Here we will describe and discuss the main classes of these substances and their mechanisms of action. We will also explore avenues of research for the development of new drugs, with a focus on the use of computational models in this field.
first_indexed 2024-03-08T10:38:42Z
format Article
id doaj.art-af2cbd7b84a74baea03b464eba699b70
institution Directory Open Access Journal
issn 1424-8247
language English
last_indexed 2024-03-08T10:38:42Z
publishDate 2024-01-01
publisher MDPI AG
record_format Article
series Pharmaceuticals
spelling doaj.art-af2cbd7b84a74baea03b464eba699b702024-01-26T18:06:00ZengMDPI AGPharmaceuticals1424-82472024-01-011719210.3390/ph17010092Chemical Adjustment of FibrinolysisAlexey M. Shibeko0Ivan S. Ilin1Nadezhda A. Podoplelova2Vladimir B. Sulimov3Mikhail A. Panteleev4Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences, 109029 Moscow, RussiaResearch Computing Center, Lomonosov Moscow State University, 119991 Moscow, RussiaCenter for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences, 109029 Moscow, RussiaResearch Computing Center, Lomonosov Moscow State University, 119991 Moscow, RussiaCenter for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences, 109029 Moscow, RussiaFibrinolysis is the process of the fibrin–platelet clot dissolution initiated after bleeding has been stopped. It is regulated by a cascade of proteolytic enzymes with plasmin at its core. In pathological cases, the balance of normal clot formation and dissolution is replaced by a too rapid lysis, leading to bleeding, or an insufficient one, leading to an increased thrombotic risk. The only approved therapy for emergency thrombus lysis in ischemic stroke is recombinant tissue plasminogen activator, though streptokinase or urokinase-type plasminogen activators could be used for other conditions. Low molecular weight compounds are of great interest for long-term correction of fibrinolysis dysfunctions. Their areas of application might go beyond the hematology field because the regulation of fibrinolysis could be important in many conditions, such as fibrosis. They enhance or weaken fibrinolysis without significant effects on other components of hemostasis. Here we will describe and discuss the main classes of these substances and their mechanisms of action. We will also explore avenues of research for the development of new drugs, with a focus on the use of computational models in this field.https://www.mdpi.com/1424-8247/17/1/92thrombolysisfibrinplasmintissue plasminogen activatorischemic stroke
spellingShingle Alexey M. Shibeko
Ivan S. Ilin
Nadezhda A. Podoplelova
Vladimir B. Sulimov
Mikhail A. Panteleev
Chemical Adjustment of Fibrinolysis
Pharmaceuticals
thrombolysis
fibrin
plasmin
tissue plasminogen activator
ischemic stroke
title Chemical Adjustment of Fibrinolysis
title_full Chemical Adjustment of Fibrinolysis
title_fullStr Chemical Adjustment of Fibrinolysis
title_full_unstemmed Chemical Adjustment of Fibrinolysis
title_short Chemical Adjustment of Fibrinolysis
title_sort chemical adjustment of fibrinolysis
topic thrombolysis
fibrin
plasmin
tissue plasminogen activator
ischemic stroke
url https://www.mdpi.com/1424-8247/17/1/92
work_keys_str_mv AT alexeymshibeko chemicaladjustmentoffibrinolysis
AT ivansilin chemicaladjustmentoffibrinolysis
AT nadezhdaapodoplelova chemicaladjustmentoffibrinolysis
AT vladimirbsulimov chemicaladjustmentoffibrinolysis
AT mikhailapanteleev chemicaladjustmentoffibrinolysis