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Ciraparantag (PER977) Sale

(Synonyms: (2S,2'S)-N,N'-(1,4-哌嗪二基二-3,1-丙烷二基)二[2-氨基-5-[(氨基亚胺甲基)氨基]戊酰胺]) 目录号 : GC32473

Ciraparantag是凝血酶和Xa的抑制剂,除了VKAs以外对所有的凝血剂都有对抗作用

Ciraparantag (PER977) Chemical Structure

Cas No.:1438492-26-2

规格 价格 库存 购买数量
1mg
¥982.00
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5mg
¥2,499.00
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10mM (in 1mL Water)
¥2,818.00
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50mg
¥8,479.00
现货
100mg
¥13,388.00
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Sample solution is provided at 25 µL, 10mM.

产品文档

Quality Control & SDS

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产品描述

Ciraparantag is a thrombin and factor Xa inhibitors as well as to heparin-based anticoagulants through non-covalent hydrogen bonding and charge interactions. It is reported to antagonize the effects of all coagulants except VKAs and agratroban. [1][2]

[1]. Arundhati Das et al. Novel antidotes for target specific oral anticoagulants. Exp Hematol Oncol, 2015, 4: 25. [2]. Tiffany Y Hu et al. Reversing anticoagulant effects of novel oral anticoagulants: role of ciraparantag, andexanet alfa, and idarucizumab. Vasc Health Risk Manag, 2016, 12: 35-44.

Chemical Properties

Cas No. 1438492-26-2 SDF
别名 (2S,2'S)-N,N'-(1,4-哌嗪二基二-3,1-丙烷二基)二[2-氨基-5-[(氨基亚胺甲基)氨基]戊酰胺]
Canonical SMILES O=C(NCCCN1CCN(CCCNC([C@@H](N)CCCNC(N)=N)=O)CC1)[C@@H](N)CCCNC(N)=N
分子式 C22H48N12O2 分子量 512.7
溶解度 Water : ≥ 31 mg/mL (60.46 mM) 储存条件 Store at -20°C
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1 mg 5 mg 10 mg
1 mM 1.9505 mL 9.7523 mL 19.5046 mL
5 mM 0.3901 mL 1.9505 mL 3.9009 mL
10 mM 0.195 mL 0.9752 mL 1.9505 mL
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Research Update

Ciraparantag, an anticoagulant reversal drug: mechanism of action, pharmacokinetics, and reversal of anticoagulants

Blood 2021 Jan 7;137(1):115-125.PMID:33205809DOI:10.1182/blood.2020007116.

Ciraparantag, an anticoagulant reversal agent, is a small molecule specifically designed to bind noncovalently by charge-charge interaction to unfractionated heparin and low-molecular-weight heparin. It shows binding characteristics that are similar to those of direct oral anticoagulants (DOACs). A dynamic light-scattering methodology was used to demonstrate Ciraparantag's binding to the heparins and DOACs and its lack of binding to a variety of proteins including coagulation factors and commonly used drugs. Ciraparantag reaches maximum concentration within minutes after IV administration with a half-life of 12 to 19 minutes. It is primarily hydrolyzed by serum peptidases into 2 metabolites, neither of which has substantial activity. Ciraparantag and its metabolites are recovered almost entirely in the urine. In animal models of bleeding (rat tail transection and liver laceration), a single IV dose of Ciraparantag given at peak concentrations of the anticoagulant, but before the bleeding injury, significantly reduced the blood loss. Ciraparantag, given after the bleeding injury, also significantly reduced blood loss. It appears to have substantial ability to reduce blood loss in animal models in which a variety of anticoagulants are used and has potential as a useful DOAC reversal agent.

Ciraparantag reverses the anticoagulant activity of apixaban and rivaroxaban in healthy elderly subjects

Eur Heart J 2022 Mar 7;43(10):985-992.PMID:34534272DOI:10.1093/eurheartj/ehab637.

Aims: Ciraparantag is a reversal agent for anticoagulants including direct oral anticoagulants. The aim was to evaluate the efficacy and safety of Ciraparantag to reverse anticoagulation induced by apixaban or rivaroxaban in healthy elderly adults. Methods and results: Two randomized, placebo-controlled, dose-ranging trials conducted in healthy subjects aged 50-75 years. Subjects received apixaban (Study 1) 10 mg orally twice daily for 3.5 days or rivaroxaban (Study 2) 20 mg orally once daily for 3 days. At steady-state anticoagulation subjects were randomized 3:1 to a single intravenous dose of Ciraparantag (Study 1: 30, 60, or 120 mg; Study 2: 30, 60, 120, or 180 mg) or placebo. Efficacy was based on correction of the whole blood clotting time (WBCT) at multiple timepoints over 24 h. Subjects and technicians performing WBCT testing were blinded to treatment. Complete reversal of WBCT within 1 h post-dose and sustained through 5 h (apixaban) or 6 h (rivaroxaban) was dose related and observed with apixaban in 67%, 100%, 100%, and 17% of subjects receiving Ciraparantag 30 mg, 60 mg, 120 mg, or placebo, respectively; and with rivaroxaban in 58%, 75%, 67%, 100%, and 13% of subjects receiving Ciraparantag 30 mg, 60 mg, 120 mg, 180 mg, or placebo, respectively. Adverse events related to Ciraparantag were mild, transient hot flashes or flushing. Conclusions: Ciraparantag provides a dose-related reversal of anticoagulation induced by steady-state dosing of apixaban or rivaroxaban. Sustained reversal was achieved with 60 mg Ciraparantag for apixaban and 180 mg Ciraparantag for rivaroxaban. All doses of Ciraparantag were well tolerated.

A short review of Ciraparantag in perspective of the currently available anticoagulant reversal agents

Drug Discov Today 2022 Oct;27(10):103332.PMID:35933085DOI:10.1016/j.drudis.2022.07.017.

Despite the improved safety-profile of direct oral anticoagulants (DOACs), bleeding complications remain an important side effect of anticoagulant treatment. Although anticoagulant-specific antidotes are available, an universal anticoagulant reversal agent in case of life-threatening bleeding or emergency surgery is not yet available. Ciraparantag, a synthetic small molecule that inactivates heparins and DOAC, is a promising new reversal agent that has been investigated in phase 2 trials. In this short review we provide an overview of the preclinical and clinical evidence of Ciraparantag, and compare strengths and weaknesses of Ciraparantag and the currently available anticoagulant reversal strategies.

Ciraparantag safely and completely reverses the anticoagulant effects of low molecular weight heparin

Thromb Res 2016 Oct;146:113-118.PMID:27470323DOI:10.1016/j.thromres.2016.07.008.

Major bleeding with low molecular weight heparin (LMWH) therapy occurs in up to 5% of patients and its anticoagulation is only partially reversed by protamine sulfate. We studied the ability of Ciraparantag (PER977), a novel agent that reverses LMWH in preclinical studies, to reverse LMWH in healthy volunteers. Methods: In this phase 1/2 trial, 4 cohorts of 10 healthy volunteers received escalating doses of ciraparantag (100 to 300mg) or placebo (8:2 ratio) approximately 4h after a single subcutaneous dose of enoxaparin, 1.5mg/kg. Safety, pharmacokinetic and pharmacodynamic effects were assessed. Results: Complete reversal of enoxaparin anticoagulation, measured by a reduction of whole blood clotting time, was observed in all subjects who received a single ciraparantag dose ranging from 100mg to 300mg. The anticoagulation reversal occurred rapidly after bolus injection and persisted for the duration of the study. At 12h and 24h, the differences in whole blood clotting time in the treated group compared to placebo were no longer significant, consistent with the decline in enoxaparin concentrations and anticoagulation effects. No procoagulant signals were detected as measured by D-dimer, F1.2, and tissue factor pathway inhibitor levels. Ciraparantag was well tolerated with only transient, minor side effects. Conclusion: Ciraparantag reverses the whole blood clotting time induced by enoxaparin in a dose related manner and produces no procoagulant signal or deleterious adverse events in doses up to 300mg.

Single-dose ciraparantag safely and completely reverses anticoagulant effects of edoxaban

Thromb Haemost 2017 Jan 26;117(2):238-245.PMID:27853809DOI:10.1160/TH16-03-0224.

Of the new direct oral anticoagulants, direct factor Xa inhibitors are limited by the absence of a proven reversal agent. We assessed the safety, tolerability and impact on anticoagulation reversal of Ciraparantag (PER977) alone and following a 60 mg dose of the FXa inhibitor edoxaban. Escalating, single IV doses of ciraparantag were administered alone and following a 60 mg oral dose of edoxaban in a double-blind, placebo-controlled fashion to healthy subjects. Serial assessments of the pharmacokinetics and pharmacodynamic effects of ciraparantag were performed. Eighty male subjects completed the study. Following edoxaban (60 mg), a single IV dose of ciraparantag (100 to 300 mg) demonstrated full reversal of anticoagulation within 10 minutes and sustained for 24 hours. Fibrin diameter within clots was restored to normal 30 minutes after a single dose of 100 to 300 mg ciraparantag as determined by scanning electron microscopy and change in fibrin diameter quantified by automated image analysis. Potentially related adverse events were periorbital and facial flushing and cool sensation following IV injection of ciraparantag. Renal excretion of ciraparantag metabolite was the main elimination route. There was no evidence of procoagulant activity following ciraparantag as assessed by D-dimer, prothrombin fragments 1.2, and tissue factor pathway inhibitor levels. In conclusion, ciraparantag in healthy subjects is safe and well tolerated with minor, non-dose limiting adverse events. Baseline haemostasis was restored from the anticoagulated state with doses of 100 to 300 mg ciraparantag within 10-30 minutes of administration and sustained for at least 24 hours.