| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| Other Sizes |
| Targets |
Ciraparantag targets thrombin and factor Xa inhibitors as well as heparins. It acts as a broad-spectrum reversal agent by binding non-covalently to anticoagulant molecules through hydrogen bonding and charge interactions. This binding neutralizes the anticoagulant activity of direct oral anticoagulants (DOACs), low molecular weight heparin, and unfractionated heparin, allowing for the restoration of normal coagulation.
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| ln Vitro |
Ciraparantag is a small molecule antidote for several direct oral anticoagulants (DOACs), low molecular weight heparin (LMWH), and unfractionated heparin (UFH) [2]. Synthetic cationic small molecule ciraparantag binds unfractionated low molecular weight heparin (LMWH), direct Xa inhibitors, and direct thrombin inhibitors via charge interactions and non-covalent hydrogen bonding [3].
In vitro, Ciraparantag demonstrates potent binding to various anticoagulants including DOACs (e.g., rivaroxaban, apixaban, edoxaban, dabigatran), LMWH (e.g., enoxaparin), and UFH. The compound neutralizes the anti-factor Xa and anti-factor IIa activities of these anticoagulants in plasma-based coagulation assays. It shows concentration-dependent reversal of anticoagulant effects in spiked human plasma samples. Specific IC50 values for neutralization of various anticoagulants are available from published studies. |
| ln Vivo |
In vivo, Ciraparantag has been shown to effectively reverse anticoagulation in animal models and human clinical trials. It rapidly restores normal coagulation parameters (e.g., thrombin generation, prothrombin time, and activated partial thromboplastin time) in animals treated with DOACs or heparins. The compound has demonstrated efficacy in bleeding models, reducing blood loss and improving hemostasis. Clinical trials have evaluated its safety and efficacy in healthy volunteers and patients requiring anticoagulation reversal.
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| Enzyme Assay |
In vitro assays for anticoagulant reversal typically use plasma-based coagulation assays such as prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin time (TT). Ciraparantag is incubated with anticoagulant-spiked human plasma at varying concentrations, and the coagulation parameters are measured using a coagulometer. The degree of reversal is expressed as the percentage normalization of coagulation time. Anti-factor Xa and anti-factor IIa chromogenic assays are also used to quantify the neutralization of specific anticoagulant activities.
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| Cell Assay |
Cellular assays for anticoagulant reversal are not typically performed as the compound acts directly on anticoagulant molecules in the plasma rather than on cellular targets. However, whole blood clotting assays (e.g., rotational thromboelastometry - ROTEM or thromboelastography - TEG) are used to assess the compound's ability to restore global hemostatic function in whole blood. These assays measure clot formation time, clot strength, and fibrinolysis in the presence of anticoagulants and Ciraparantag.
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| Animal Protocol |
In vivo animal studies for anticoagulant reversal typically use rat, rabbit, or dog models. Animals are administered an anticoagulant (DOAC or heparin) followed by Ciraparantag at various doses. Coagulation parameters (PT, aPTT, anti-Xa activity) are measured at baseline, after anticoagulant administration, and after Ciraparantag administration. Bleeding models (e.g., tail transection or kidney incision) are used to assess the compound's ability to reduce blood loss and restore hemostasis.
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| ADME/Pharmacokinetics |
Ciraparantag is administered intravenously for rapid reversal of anticoagulation. As a water-soluble cationic molecule, it has favorable physicochemical properties for intravenous administration. The compound has a short half-life consistent with its mechanism of action (direct binding and neutralization of anticoagulants). It is eliminated primarily via the kidneys. Detailed PK parameters such as half-life, clearance, and volume of distribution are available from clinical studies.
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| Toxicity/Toxicokinetics |
Toxicity studies of Ciraparantag have been conducted in preclinical species and in clinical trials. The compound is generally well-tolerated at therapeutic doses. Common side effects include infusion-related reactions such as flushing, headache, and nausea. Serious adverse effects are rare. The compound has been evaluated in clinical trials for safety and efficacy in healthy volunteers and patients requiring anticoagulation reversal. No significant organ toxicity has been reported.
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| References | |
| Additional Infomation |
Ciraparantag is an N-alkylpiperazine. Ciraparantag is being investigated in the clinical trial NCT01826266 (double-blind, single-dose PER977 alone and after a single-dose Edoxaban).
Ciraparantag (PER977, Aripazine) is a novel, potent, broad-spectrum reversal agent for anticoagulants including DOACs, UFH, and LMWH. It is a water-soluble, cationic small molecule that binds non-covalently to anticoagulants through hydrogen bonding and charge interactions, neutralizing their activity. The compound has been studied in clinical trials for the reversal of anticoagulation in patients requiring urgent surgery or experiencing major bleeding. It represents a promising antidote for the management of anticoagulant-associated bleeding. |
| Molecular Formula |
C22H48N12O2
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|---|---|
| Molecular Weight |
512.71
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| Exact Mass |
512.402
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| CAS # |
1438492-26-2
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| Related CAS # |
1438492-26-2;1565823-56-4 (acetate 1:6);1644388-83-9 (acetate 1:1);
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| PubChem CID |
71576543
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| Appearance |
White to off-white solid powder
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| LogP |
1.237
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| Hydrogen Bond Donor Count |
8
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
18
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| Heavy Atom Count |
36
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| Complexity |
629
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C1CN(CCN1CCCNC(=O)[C@H](CCCN=C(N)N)N)CCCNC(=O)[C@H](CCCN=C(N)N)N
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| InChi Key |
HRDUUSCYRPOMSO-ROUUACIJSA-N
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| InChi Code |
InChI=1S/C22H48N12O2/c23-17(5-1-7-31-21(25)26)19(35)29-9-3-11-33-13-15-34(16-14-33)12-4-10-30-20(36)18(24)6-2-8-32-22(27)28/h17-18H,1-16,23-24H2,(H,29,35)(H,30,36)(H4,25,26,31)(H4,27,28,32)/t17-,18-/m0/s1
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| Chemical Name |
(2S,2'S)-N,N'-(piperazine-1,4-diylbis(propane-3,1-diyl))bis(2-amino-5-guanidinopentanamide)
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| Synonyms |
PER977 AripazinePER 977PER-977 Ciraparantag
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
H2O : ≥ 31 mg/mL (~60.46 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9504 mL | 9.7521 mL | 19.5042 mL | |
| 5 mM | 0.3901 mL | 1.9504 mL | 3.9008 mL | |
| 10 mM | 0.1950 mL | 0.9752 mL | 1.9504 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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