Ciraparantag

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).^[1][2]

Ciraparantag

Clinical data
Other names	PER977; N1,N1′-[Piperazine-1,4-diylbis(propane-1,3-diyl)]bis-L-argininamide
Routes of administration	Intravenous
ATC code	None
Legal status
Legal status	Investigational
Pharmacokinetic data
Onset of action	10 min
Duration of action	24 hours
Identifiers
IUPAC name (2S)-2-Amino-N-[3-[4-[3-[[(2S)-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]propyl]piperazin-1-yl]propyl]-5-(diaminomethylideneamino)pentanamide
CAS Number	1438492-26-2
PubChem CID	71576543
ChemSpider	33427375
UNII	U2R67KV65Q
KEGG	D10868 Y
CompTox Dashboard (EPA)	DTXSID701045783
Chemical and physical data
Formula	C22H48N12O2
Molar mass	512.708 g·mol−1
3D model (JSmol)	Interactive image
SMILES C1CN(CCN1CCCNC(=O)[C@H](CCCNC(=N)N)N)CCCNC(=O)[C@H](CCCNC(=N)N)N
InChI 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 Key:HRDUUSCYRPOMSO-ROUUACIJSA-N

Medical uses

Ciraparantag significantly reverses anticoagulation induced by a therapeutic dose of edoxaban within 10 minutes following injection.^[3] This return to normal haemostasis persists over 24 hours following a single intravenous dose of the drug.^[4] In addition to edoxaban, it also reverses the actions of LMWH and dabigatran.^[5]

Pharmacology

Mechanism of action

According to in vitro studies, the substance binds directly to anticoagulants via hydrogen bonds and charge-charge interactions ^[3] from or to various parts of the molecule:^[1]

Hydrogen bonds	Rivaroxaban	Apixaban	Edoxaban	Dabigatran	Heparins
Guanidine part	Y		Y	Y	Y
α-Amino group	Y	Y		Y	Y
Amide nitrogen	Y			Y	Y
Amide oxygen		Y	Y

Chemistry

Ciraparantag consists of two L-arginine units connected with a piperazine containing linker chain.^[1]

See also

• Andexanet alfa
• Idarucizumab
• Prothrombin complex concentrate
• Vitamin K