Ciraparantag Explained

Iupac Name:	(2S)-2-Amino-N-[3-[4-[3-[[(2''S'')-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]propyl]piperazin-1-yl]propyl]-5-(diaminomethylideneamino)pentanamide
Legal Status:	Investigational
Routes Of Administration:	Intravenous
Onset:	10 min
Duration Of Action:	24 hours
Cas Number:	1438492-26-2
Atc Prefix:	None
Pubchem:	71576543
Chemspiderid:	33427375
Unii:	U2R67KV65Q
Kegg:	D10868
Synonyms:	PER977; N¹,N^1′-[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).^[1] ^[2]

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.^[3] In addition to edoxaban, it also reverses the actions of LMWH and dabigatran.^[4]

Pharmacology

Mechanism of action

According to in vitro studies, the substance binds directly to anticoagulants via hydrogen bonds and charge-charge interactions ^[5] from or to various parts of the molecule:

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

Chemistry

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

Notes and References

Book: Schubert-Zsilavecz M, Wurglics M . Neue Arzneimittel . Fall 2015 . German .
Ansell JE . 7364744 . Universal, class-specific and drug-specific reversal agents for the new oral anticoagulants . Journal of Thrombosis and Thrombolysis . 41 . 2 . 248–52 . February 2016 . 26449414 . 10.1007/s11239-015-1288-1 .
Laulicht B, Bakhru S, Jiang X, Chen L, Pan D, Grosso M, Morishima Y, Brown K, Masumoto H, Costin J, Steiner S . Antidote for new oral anticoagulants: mechanism of action and binding specificity of PER977. . J Thromb Haemost . June 2013 . 11 . suppl 2 . 1–84 .
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. 10.1016/S0735-1097(15)62056-3.
Ansell JE, Bakhru SH, Laulicht BE, Steiner SS, Grosso MA, Brown K, Dishy V, Lanz HJ, Mercuri MF, Noveck RJ, Costin JC . 6 . Single-dose ciraparantag safely and completely reverses anticoagulant effects of edoxaban . Thrombosis and Haemostasis . 117 . 2 . 238–245 . January 2017 . 27853809 . 6260118 . 10.1160/TH16-03-0224 .