Cangrelor is the only currently available intravenous platelet P2Y12 receptor inhibitor, and its quick onset and offset make it an appealing option for antiplatelet therapy[1]. In vitro, the experiment focused on αIIbβ3 complex (platelet receptor for fibrinogen), and cangrelor (140μM, 15 min) suppressed the expression of this surface membrane activation marker in platelets[2]. Cangrelor tetrasodium (10 mg/kg) not only significantly decreases BLM-induced release of inflammatory cytokines (PF4, CD40 L and MPO), but also decreases the increment of platelets, neutrophils and platelet-neutrophil aggregates in the fibrotic lung and in the peripheral blood of BLM-treated mice[3].
Cangrelor tetrasodium 细胞实验
Cell Line
Concentration
Treated Time
Description
References
BV-2 cells
20, 40, 80 μM
24 hours
To evaluate the inhibitory effect of Cangrelor on LPS-induced inflammatory response in BV-2 cells. Results showed that Cangrelor significantly inhibited LPS-induced release of TNF-α, IL-1β, and IL-6, downregulated NF-κB p65 expression, and upregulated p-CREB and BDNF expression.
J Neuroinflammation. 2023 Nov 21;20(1):271.
BLA glutamatergic neurons
100 nmol/L
Cangrelor inhibition of GPR17 reversed the CRS-induced increase in firing rate and decrease in rheobase of BLA glutamatergic neurons.
Acta Pharm Sin B. 2024 Nov;14(11):4789-4805.
Platelets
200 µM
2 minutes
To test the effect of Cangrelor on platelet S1P release, results showed that Cangrelor inhibited S1P release
Nat Commun. 2023 Apr 26;14(1):2404.
Murine platelets
100 nM
10 minutes
To study the effect of P2Y12 receptor antagonist on platelet aggregation, results showed that Cangrelor significantly inhibited platelet aggregation.
J Thromb Haemost. 2011 Apr;9(4):810-9.
CHO-K1 cells
0.5 ± 0.1 nM
12 minutes
To assess the partial agonist effect of AR-C69931MX on P2Y13 receptor, results showed AR-C69931MX as a partial agonist inhibiting cAMP accumulation.
Cell Mol Life Sci. 2005 Nov;62(21):2508-15.
HepG2 cells
100 nM
10 minutes
To evaluate the effect of AR-C69931MX on TG-HDL2 internalization, results showed that AR-C69931MX alone increased TG-HDL2 internalization more than ADP.
Cell Mol Life Sci. 2005 Nov;62(21):2508-15.
Cangrelor tetrasodium 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
FeCl3-induced carotid artery thrombosis model
Intravenous injection
30 μg/kg
Single injection
Comparison of the antithrombotic effects of M3mP6 HLPN with the intravenous P2Y12 inhibitor cangrelor, showing that cangrelor had similar effects to M3mP6 HLPN in most mice but was more effective in some mice
Sci Transl Med. 2020 Jul 15;12(552):eaaz7287
ICR mice
LPS-induced cognitive impairment model
Microinjection into hippocampal DG region
2.0 μg and 4.0 μg
Daily administration for 3 weeks
To evaluate the ameliorative effect of Cangrelor on LPS-induced cognitive impairment in mice. Results showed that Cangrelor pretreatment significantly improved LPS-induced spatial learning and memory deficits, reduced neuroinflammation and oxidative stress, and inhibited hippocampal neuronal apoptosis.
J Neuroinflammation. 2023 Nov 21;20(1):271.
C57BL/6J mice
Chronic restraint stress (CRS) model
Bilateral BLA injection
0.5 nmol/site, 1 nmol/mouse
Once daily for 3 consecutive days
Cangrelor significantly ameliorated CRS-induced anxiety-like behaviors in mice, including increased time spent in open arms and entries of open arms, decreased time in closed arms and entries of closed arms in EPM test; increased time in center in OFT; reduced latency to feed in NSF test.
Acta Pharm Sin B. 2024 Nov;14(11):4789-4805.
Mice
Acute myocardial infarction model
Intravenous injection
200 µM
Single administration
To test the protective effect of Cangrelor on myocardial infarction, results showed that Cangrelor failed to protect the myocardium
Nat Commun. 2023 Apr 26;14(1):2404.
Mice
Low-density lipoprotein receptor-deficient mice (LDLR−/−) and C57Bl/6 wild-type mice
In vitro
100 nM
Single dose, lasting 10 minutes
To evaluate the effect of Cangrelor on platelet aggregation in hypercholesterolemic mice, results showed that Cangrelor significantly inhibited platelet aggregation.
J Thromb Haemost. 2011 Apr;9(4):810-9.
C57BL/6 mice
Ferric chloride-induced thrombosis model
Intravenous injection
0.2 mg/kg b.w.
Single dose
To evaluate the antithrombotic effect of Cangrelor in combination with HE-NECA, results showed that the combination significantly prolonged the time to occlusion and reduced the ratio of total occlusion.
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