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.

中文翻译：

---

Ir-6：一种抑制人血小板活化的新型铱（III）有机金属衍生物。

据报道血小板活化在动脉血栓形成，癌症转移和进展中起主要作用。最近，我们开发了一种新型的基于Ir（III）的化合物，[Ir（Cp ）1-（2-吡啶基）-3-（4-二甲基氨基苯基）咪唑并[1,5-a]吡啶Cl] BF ₄或Ir- 6并评估其作为抗血小板药的有效性。Ir-6对胶原蛋白刺激的人血小板聚集表现出更高的效力。Ir-6还抑制ATP释放，细胞内Ca ²⁺动员，P-选择素表达以及磷脂酶Cγ2（PLCγ2），胶原蛋白活化的血小板中的蛋白激酶C（PKC），v-Akt鼠胸腺瘤病毒致癌基因（Akt）/蛋白激酶B和促分裂原激活的蛋白激酶（MAPK）。腺苷酸环化酶抑制剂SQ22536或鸟苷酸环化酶抑制剂1H- [1,2,4]恶二唑并[4,3-a]喹喔啉-1-酮均不能显着逆转Ir-6介导的胶原诱导的血小板聚集抑制作用。而且，Ir-6在胶原蛋白活化的血小板或Fenton反应溶液中并未显着降低OH自由基信号。在2 mg / kg时，Ir-6明显延长了实验小鼠的出血时间。总之，IR-6起着通过信号通路，如PLC的抑制抑制血小板活化至关重要的作用γ2-PKC级联反应以及随后对Akt和MAPK激活的抑制，从而最终抑制了血小板聚集。因此，Ir-6是用于预防或治疗血栓栓塞性疾病或破坏血小板与肿瘤细胞之间相互作用的潜在治疗剂，这有助于肿瘤细胞的生长和发展。