EP-217609

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C95H151N11O59S8
Molecular Weight	2647.774
Optical Activity	UNSPECIFIED
Defined Stereocenters	31 / 31
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@]12CS[C@@H](CCCCC(=O)NCCCC[C@H](NC(=O)CCCNC(=O)C[C@H](NS(=O)(=O)C3=C(C)C(C)=C(OC)C=C3C)C(=O)N[C@H](CC4=CC=C(C=C4)C(N)=N)C(=O)N5CCCCC5)C(=O)NCCOCCOCCOCCO[C@@H]6[C@@H](COS(O)(=O)=O)O[C@H](O[C@@]7([H])[C@H](OC)[C@@H](OC)[C@H](O[C@]8([H])[C@@H](COS(O)(=O)=O)O[C@H](O[C@@]9([H])[C@H](OC)[C@@H](OC)[C@H](O[C@]%10([H])[C@@H](COS(O)(=O)=O)O[C@H](OC)[C@H](OS(O)(=O)=O)[C@H]%10OC)O[C@H]9C(O)=O)[C@H](OS(O)(=O)=O)[C@H]8OS(O)(=O)=O)O[C@@H]7C(O)=O)[C@H](OC)[C@H]6OC)[C@@]1([H])NC(=O)N2

InChI

InChIKey=QIBHGITUGYXJDF-UDLCEBFESA-N

InChI=1S/C95H151N11O59S8/c1-48-41-57(138-4)49(2)50(3)83(48)167(118,119)105-54(86(111)102-55(87(112)106-32-18-13-19-33-106)42-51-25-27-52(28-26-51)84(96)97)43-64(109)99-30-20-24-63(108)101-53(21-16-17-29-98-62(107)23-15-14-22-61-65-56(47-166-61)103-95(117)104-65)85(110)100-31-34-147-35-36-148-37-38-149-39-40-150-66-58(44-151-168(120,121)122)155-91(78(143-9)69(66)139-5)159-73-71(141-7)80(145-11)93(162-76(73)88(113)114)158-68-60(46-153-170(126,127)128)156-94(82(165-173(135,136)137)75(68)163-171(129,130)131)160-74-72(142-8)79(144-10)92(161-77(74)89(115)116)157-67-59(45-152-169(123,124)125)154-90(146-12)81(70(67)140-6)164-172(132,133)134/h25-28,41,53-56,58-61,65-82,90-94,105H,13-24,29-40,42-47H2,1-12H3,(H3,96,97)(H,98,107)(H,99,109)(H,100,110)(H,101,108)(H,102,111)(H,113,114)(H,115,116)(H2,103,104,117)(H,120,121,122)(H,123,124,125)(H,126,127,128)(H,129,130,131)(H,132,133,134)(H,135,136,137)/t53-,54-,55+,56-,58+,59+,60+,61-,65-,66+,67+,68+,69-,70-,71-,72-,73-,74-,75-,76-,77+,78+,79+,80+,81+,82+,90-,91+,92+,93+,94+/m0/s1

HIDE SMILES / InChI

Molecular Formula	C95H151N11O59S8
Molecular Weight	2647.774
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	31 / 31
E/Z Centers	1
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25374268 | http://drugprofiles.informa.com/drug_profiles/8650-ep217609%2Favidin | https://adisinsight.springer.com/drugs/800033781 | https://www.sofinnova.fr/en/endotis-pharma-has-initiated-a-phase-i-program-with-the-neutralizable-anticoagulant-ep217609-and-its-specific-antidote-avidin-and-signed-a-manufacturing-and-co-development-agreement-with-sigma-tau-fo/ | https://www.ncbi.nlm.nih.gov/pubmed/22144183

EP-217609 is a new synthetic parenteral dual-action anticoagulant combining a direct thrombin inhibitor (α-NAPAP analog), an indirect factor Xa inhibitor (fondaparinux analog) and a biotin moiety allowing its neutralisation. EP-217609 is the biotinylated form of EP42675. As announced in May 2009, EP42675 has successfully completed a phase I program in 100 healthy subjects. EP42675 was well tolerated and showed predictable pharmacokinetic (PK) and pharmacodynamic (PD) profiles with low intra- and intersubject variabilities. In animals, the PK/PD profiles of EP-217609 and EP42675 are similar. EP-217609 exhibited similar in vitro anticoagulant properties as its parent compounds. EP-217609 exhibits an unprecedented pharmacologic profile in showing high bioavailability, long plasma half-life, and potent antithrombotic activity in animals without the complications of thrombin rebound. EP-217609 is administered intravenously or subcutaneously at fixed dose without need for monitoring. EP-217609 was in Phase-II clinical trials in thrombosis prevention in France (IV), but development of EP-217609 appears to have been discontinued.

Originator

Approval Year

PubMed

Title	Date	PubMed
EP217609, a neutralisable dual-action FIIa/FXa anticoagulant, with antithrombotic effects in arterial thrombosis.	2015 Feb	25374268
First in man study of EP217609, a new long-acting, neutralisable parenteral antithrombotic with a dual mechanism of action.	2016 Sep	27259709

Sample Use Guides

In Vivo Use Guide

In a randomised double-blind placebo-controlled study, healthy male subjects were administered intravenously single ascending doses (1, 3 or 10 mg) of EP-217609 or placebo. Each treatment group consisted of 10 subjects of whom 8 received EP-217609 and 2 received placebo.

Route of Administration: Intravenous

In Vitro Use Guide

EP-217609 inhibited thrombin with rapid kinetics (k(on) > 10(7)M(-1)s(-1)), a high affinity (K(I) = 30-40pM), and more than 1000-fold selectivity over other coagulation and fibrinolytic protease targets, comparing favorably with the best direct thrombin inhibitors known. EP-217609 bound antithrombin with high affinity (K(D) = 30nM) and activated the serpin to rapidly (k(ass) ∼ 10(6)M(-1)s(-1)) and selectively (> 20-fold) inhibit factor Xa.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 03:01:06 GMT 2023` Edited by `admin` on `Sat Dec 16 03:01:06 GMT 2023`
Record UNII	R6464792NG
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

EP-217609

Common Name

English

EP217609

Code

English

Classification Tree Code System Code

FDA ORPHAN DRUG

336211