Exogenous Integrin αIIbβ3 Inhibitors Revisited: Past, Present and Future Applications
The integrin αIIbβ3 is the most abundant integrin on platelets. Upon platelet activation, the integrin changes its conformation (inside-out signalling) and outside-in signalling takes place leading to platelet spreading, platelet aggregation and thrombus formation. Bloodsucking parasites such as mos...
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| Format: | Article |
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MDPI AG
2021-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/7/3366 |
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| author | Danique L. van den Kerkhof Paola E.J. van der Meijden Tilman M. Hackeng Ingrid Dijkgraaf |
| author_facet | Danique L. van den Kerkhof Paola E.J. van der Meijden Tilman M. Hackeng Ingrid Dijkgraaf |
| author_sort | Danique L. van den Kerkhof |
| collection | DOAJ |
| description | The integrin αIIbβ3 is the most abundant integrin on platelets. Upon platelet activation, the integrin changes its conformation (inside-out signalling) and outside-in signalling takes place leading to platelet spreading, platelet aggregation and thrombus formation. Bloodsucking parasites such as mosquitoes, leeches and ticks express anticoagulant and antiplatelet proteins, which represent major sources of lead compounds for the development of useful therapeutic agents for the treatment of haemostatic disorders or cardiovascular diseases. In addition to hematophagous parasites, snakes also possess anticoagulant and antiplatelet proteins in their salivary glands. Two snake venom proteins have been developed into two antiplatelet drugs that are currently used in the clinic. The group of proteins discussed in this review are disintegrins, low molecular weight integrin-binding cysteine-rich proteins, found in snakes, ticks, leeches, worms and horseflies. Finally, we highlight various oral antagonists, which have been tested in clinical trials but were discontinued due to an increase in mortality. No new αIIbβ3 inhibitors are developed since the approval of current platelet antagonists, and structure-function analysis of exogenous disintegrins could help find platelet antagonists with fewer adverse side effects. |
| first_indexed | 2024-03-10T12:54:26Z |
| format | Article |
| id | doaj.art-a7613a8c0e654d88bc4ab2dfb7062d4e |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T12:54:26Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a7613a8c0e654d88bc4ab2dfb7062d4e2023-11-21T12:01:15ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-03-01227336610.3390/ijms22073366Exogenous Integrin αIIbβ3 Inhibitors Revisited: Past, Present and Future ApplicationsDanique L. van den Kerkhof0Paola E.J. van der Meijden1Tilman M. Hackeng2Ingrid Dijkgraaf3Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6229 ER Maastricht, The NetherlandsDepartment of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6229 ER Maastricht, The NetherlandsDepartment of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6229 ER Maastricht, The NetherlandsDepartment of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6229 ER Maastricht, The NetherlandsThe integrin αIIbβ3 is the most abundant integrin on platelets. Upon platelet activation, the integrin changes its conformation (inside-out signalling) and outside-in signalling takes place leading to platelet spreading, platelet aggregation and thrombus formation. Bloodsucking parasites such as mosquitoes, leeches and ticks express anticoagulant and antiplatelet proteins, which represent major sources of lead compounds for the development of useful therapeutic agents for the treatment of haemostatic disorders or cardiovascular diseases. In addition to hematophagous parasites, snakes also possess anticoagulant and antiplatelet proteins in their salivary glands. Two snake venom proteins have been developed into two antiplatelet drugs that are currently used in the clinic. The group of proteins discussed in this review are disintegrins, low molecular weight integrin-binding cysteine-rich proteins, found in snakes, ticks, leeches, worms and horseflies. Finally, we highlight various oral antagonists, which have been tested in clinical trials but were discontinued due to an increase in mortality. No new αIIbβ3 inhibitors are developed since the approval of current platelet antagonists, and structure-function analysis of exogenous disintegrins could help find platelet antagonists with fewer adverse side effects.https://www.mdpi.com/1422-0067/22/7/3366plateletsintegrin αIIbβ3antagonistshematophagous parasites |
| spellingShingle | Danique L. van den Kerkhof Paola E.J. van der Meijden Tilman M. Hackeng Ingrid Dijkgraaf Exogenous Integrin αIIbβ3 Inhibitors Revisited: Past, Present and Future Applications International Journal of Molecular Sciences platelets integrin αIIbβ3 antagonists hematophagous parasites |
| title | Exogenous Integrin αIIbβ3 Inhibitors Revisited: Past, Present and Future Applications |
| title_full | Exogenous Integrin αIIbβ3 Inhibitors Revisited: Past, Present and Future Applications |
| title_fullStr | Exogenous Integrin αIIbβ3 Inhibitors Revisited: Past, Present and Future Applications |
| title_full_unstemmed | Exogenous Integrin αIIbβ3 Inhibitors Revisited: Past, Present and Future Applications |
| title_short | Exogenous Integrin αIIbβ3 Inhibitors Revisited: Past, Present and Future Applications |
| title_sort | exogenous integrin αiibβ3 inhibitors revisited past present and future applications |
| topic | platelets integrin αIIbβ3 antagonists hematophagous parasites |
| url | https://www.mdpi.com/1422-0067/22/7/3366 |
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