Ir-6: A Novel Iridium (III) Organometallic Derivative for Inhibition of Human Platelet Activation
Joint Authors
Hsia, Chih-Hsuan
Shyu, Ren-Shi
Khamrang, Themmila
Hsia, Chih-Wei
Velusamy, Marappan
Chou, Duen-Suey
Sheu, Joen-Rong
Chang, Chao-Chien
Source
Bioinorganic Chemistry and Applications
Issue
Vol. 2018, Issue 2018 (31 Dec. 2018), pp.1-14, 14 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2018-05-02
Country of Publication
Egypt
No. of Pages
14
Main Subjects
Abstract EN
Platelet activation has been reported to play a major role in arterial thrombosis, cancer metastasis, and progression.
Recently, we developed a novel Ir(III)-based compound, [Ir(Cp∗)1-(2-pyridyl)-3-(4-dimethylaminophenyl)imidazo[1,5-a]pyridine Cl]BF4 or Ir-6 and assessed its effectiveness as an antiplatelet drug.
Ir-6 exhibited higher potency against human platelet aggregation stimulated by collagen.
Ir-6 also inhibited ATP-release, intracellular Ca2+ mobilization, P-selectin expression, and the phosphorylation of phospholipase Cγ2 (PLCγ2), protein kinase C (PKC), v-Akt murine thymoma viral oncogene (Akt)/protein kinase B, and mitogen-activated protein kinases (MAPKs), in collagen-activated platelets.
Neither the adenylate cyclase inhibitor SQ22536 nor the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one significantly reversed the Ir-6-mediated inhibition of collagen-induced platelet aggregation.
Moreover, Ir-6 did not considerably diminish OH radical signals in collagen-activated platelets or Fenton reaction solution.
At 2 mg/kg, Ir-6 markedly prolonged the bleeding time in experimental mice.
In conclusion, Ir-6 plays a crucial role by inhibiting platelet activation through the inhibition of signaling pathways, such as the PLCγ2–PKC cascade and the subsequent suppression of Akt and MAPK activation, thereby ultimately inhibiting platelet aggregation.
Therefore, Ir-6 is a potential therapeutic agent for preventing or treating thromboembolic disorders or disrupting the interplay between platelets and tumor cells, which contributes to tumor cell growth and progression.
American Psychological Association (APA)
Shyu, Ren-Shi& Khamrang, Themmila& Sheu, Joen-Rong& Hsia, Chih-Wei& Velusamy, Marappan& Hsia, Chih-Hsuan…[et al.]. 2018. Ir-6: A Novel Iridium (III) Organometallic Derivative for Inhibition of Human Platelet Activation. Bioinorganic Chemistry and Applications،Vol. 2018, no. 2018, pp.1-14.
https://search.emarefa.net/detail/BIM-1123214
Modern Language Association (MLA)
Shyu, Ren-Shi…[et al.]. Ir-6: A Novel Iridium (III) Organometallic Derivative for Inhibition of Human Platelet Activation. Bioinorganic Chemistry and Applications No. 2018 (2018), pp.1-14.
https://search.emarefa.net/detail/BIM-1123214
American Medical Association (AMA)
Shyu, Ren-Shi& Khamrang, Themmila& Sheu, Joen-Rong& Hsia, Chih-Wei& Velusamy, Marappan& Hsia, Chih-Hsuan…[et al.]. Ir-6: A Novel Iridium (III) Organometallic Derivative for Inhibition of Human Platelet Activation. Bioinorganic Chemistry and Applications. 2018. Vol. 2018, no. 2018, pp.1-14.
https://search.emarefa.net/detail/BIM-1123214
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1123214