ciraparantag
{{Short description|Chemical compound}}
{{Infobox drug
| IUPAC_name = (2S)-2-Amino-N-[3-[4-[3-
| image = Ciraparantag.svg
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| legal_status = Investigational
| routes_of_administration = Intravenous
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| onset = 10 min
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| duration_of_action = 24 hours
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| CAS_number = 1438492-26-2
| ATCvet =
| ATC_prefix = None
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| PubChem = 71576543
| DrugBank =
| ChemSpiderID = 33427375
| UNII = U2R67KV65Q
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D10868
| synonyms = PER977; N1,N1′-[Piperazine-1,4-diylbis(propane-1,3-diyl)]bis-L-argininamide
| C=22 | H=48 | N=12 | O=2
| smiles = C1CN(CCN1CCCNC(=O)[C@H](CCCNC(=N)N)N)CCCNC(=O)[C@H](CCCNC(=N)N)N
| StdInChI=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
| StdInChIKey = HRDUUSCYRPOMSO-ROUUACIJSA-N
}}
Ciraparantag (aripazine) is a drug under investigation as an antidote for a number of anticoagulant (anti-blood clotting) drugs, including factor Xa inhibitors (rivaroxaban, apixaban and edoxaban), dabigatran, and heparins (including fondaparinux, low molecular weight heparins (LMWH), and unfractionated heparin).{{cite book | vauthors = Schubert-Zsilavecz M, Wurglics M | title = Neue Arzneimittel | date = Fall 2015 | language = German }}{{cite journal | vauthors = Ansell JE | s2cid = 7364744 | title = Universal, class-specific and drug-specific reversal agents for the new oral anticoagulants | journal = Journal of Thrombosis and Thrombolysis | volume = 41 | issue = 2 | pages = 248–52 | date = February 2016 | pmid = 26449414 | doi = 10.1007/s11239-015-1288-1 }}
Medical uses
Ciraparantag significantly reverses anticoagulation induced by a therapeutic dose of edoxaban within 10 minutes following injection. This return to normal haemostasis persists over 24 hours following a single intravenous dose of the drug.{{cite journal | vauthors = Laulicht B, Bakhru S, Jiang X, Chen L, Pan D, Grosso M, Morishima Y, Brown K, Masumoto H, Costin J, Steiner S | title = Antidote for new oral anticoagulants: mechanism of action and binding specificity of PER977. | journal = J Thromb Haemost | date = June 2013 | volume = 11 | issue = suppl 2 | pages = 1–84 | url = http://www.eventure-online.com/eventure/publicAbstractView.do?id=226718&congressId=6839andhttp://www.perosphere.com/content/presentations/documents/Perosphere_ISTH_Talk }} In addition to edoxaban, it also reverses the actions of LMWH and dabigatran.{{cite journal| vauthors = Costin JC, Laulicht B, Bakhru S, Steiner S |date=March 2015|title=PER977 reverses low molecular weight heparin in addition to IIa and Xa new oral anticoagulants|journal=Journal of the American College of Cardiology|volume=65|issue=10|pages=A2056|doi=10.1016/S0735-1097(15)62056-3|doi-access=}}
Pharmacology
=Mechanism of action=
According to in vitro studies, the substance binds directly to anticoagulants via hydrogen bonds and charge-charge interactions {{cite journal | vauthors = Ansell JE, Bakhru SH, Laulicht BE, Steiner SS, Grosso MA, Brown K, Dishy V, Lanz HJ, Mercuri MF, Noveck RJ, Costin JC | display-authors = 6 | title = Single-dose ciraparantag safely and completely reverses anticoagulant effects of edoxaban | journal = Thrombosis and Haemostasis | volume = 117 | issue = 2 | pages = 238–245 | date = January 2017 | pmid = 27853809 | pmc = 6260118 | doi = 10.1160/TH16-03-0224 }} from or to various parts of the molecule:
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| Hydrogen bonds
! Rivaroxaban ! Apixaban ! Edoxaban ! Dabigatran ! Heparins |
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| Guanidine part
| {{Check mark|15}} | | {{Check mark|15}} | {{Check mark|15}} | {{Check mark|15}} |
| α-Amino group
| {{Check mark|15}} | {{Check mark|15}} | | {{Check mark|15}} | {{Check mark|15}} |
| Amide nitrogen
| {{Check mark|15}} | | | {{Check mark|15}} | {{Check mark|15}} |
| Amide oxygen
| | {{Check mark|15}} | {{Check mark|15}} | | |
Chemistry
Ciraparantag consists of two L-arginine units connected with a piperazine containing linker chain.