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 namesPER977; 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 action10 min
Duration of action24 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
PubChem CID
ChemSpider
UNII
KEGG
Chemical and physical data
FormulaC22H48N12O2
Molar mass512.708 g·mol−1
3D model (JSmol)
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

References
  1. Schubert-Zsilavecz M, Wurglics M (Fall 2015). Neue Arzneimittel (in German).
  2. Ansell JE (February 2016). "Universal, class-specific and drug-specific reversal agents for the new oral anticoagulants". Journal of Thrombosis and Thrombolysis. 41 (2): 248–52. doi:10.1007/s11239-015-1288-1. PMID 26449414. S2CID 7364744.
  3. Ansell JE, Bakhru SH, Laulicht BE, Steiner SS, Grosso MA, Brown K, et al. (January 2017). "Single-dose ciraparantag safely and completely reverses anticoagulant effects of edoxaban". Thrombosis and Haemostasis. 117 (2): 238–245. doi:10.1160/TH16-03-0224. PMC 6260118. PMID 27853809.
  4. Laulicht B, Bakhru S, Jiang X, Chen L, Pan D, Grosso M, Morishima Y, Brown K, Masumoto H, Costin J, Steiner S (June 2013). "Antidote for new oral anticoagulants: mechanism of action and binding specificity of PER977". J Thromb Haemost. 11 (suppl 2): 1–84.
  5. Costin JC, Laulicht B, Bakhru S, Steiner S (March 2015). "PER977 reverses low molecular weight heparin in addition to IIa and Xa new oral anticoagulants". Journal of the American College of Cardiology. 65 (10): A2056. doi:10.1016/S0735-1097(15)62056-3.
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