ALISPORIVIR

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C63H113N11O12
Molecular Weight	1216.6378
Optical Activity	UNSPECIFIED
Defined Stereocenters	13 / 13
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](NC(=O)[C@H](C(C)C)N(CC)C(=O)[C@@H](C)N(C)C1=O)C(C)C

InChI

InChIKey=OLROWHGDTNFZBH-XEMWPYQTSA-N

InChI=1S/C63H113N11O12/c1-26-29-30-40(16)52(75)51-56(79)66-44(27-2)59(82)68(20)43(19)58(81)74(28-3)49(38(12)13)55(78)67-48(37(10)11)62(85)69(21)45(31-34(4)5)54(77)64-41(17)53(76)65-42(18)57(80)70(22)46(32-35(6)7)60(83)71(23)47(33-36(8)9)61(84)72(24)50(39(14)15)63(86)73(51)25/h26,29,34-52,75H,27-28,30-33H2,1-25H3,(H,64,77)(H,65,76)(H,66,79)(H,67,78)/b29-26+/t40-,41+,42-,43-,44+,45+,46+,47+,48+,49+,50+,51+,52-/m1/s1

HIDE SMILES / InChI

Description
Sources: https://adisinsight.springer.com/drugs/800021374 | https://www.debiopharm.com/debiopharm-international/press-releases/debiopharm-group-regains-full-rights-to-alisporivir-program/ | https://www.ncbi.nlm.nih.gov/pubmed/23440335 | https://www.ncbi.nlm.nih.gov/pubmed/21060866

Alisporivir (DEBIO-025) is a first-in-class synthetic cyclophilin inhibitor, in development with Debiopharm as an oral treatment for hepatitis C virus (HCV) infections. Alisporivir has the potential to be used for the treatment of additional diseases such as other viral infections, certain muscular dystrophies, and myocardial infarction. Alisporivir has potent anti-hepatitis C virus (HCV) activity both in vitro and in vivo. It is currently being evaluated in phase II clinical trials.

Originator

Approval Year

PubMed

Title	Date	PubMed
The non-immunosuppressive cyclosporin DEBIO-025 is a potent inhibitor of hepatitis C virus replication in vitro.	2006 Apr	16557546
Pharmacologic targeting or genetic deletion of mitochondrial cyclophilin D protects from NSAID-induced small intestinal ulceration in mice.	2010 Nov	20668000
DEB025 (Alisporivir) inhibits hepatitis C virus replication by preventing a cyclophilin A induced cis-trans isomerisation in domain II of NS5A.	2010 Oct 27	21060866

Sample Use Guides

In Vivo Use Guide

Hepatitis C: Alisporivir (ALV) 600 mg twice daily (BID) with Peginterferon alfa-2a (PEG) and ribavirin (RBV) for 1 week, followed by an additional 23 or 47 weeks according to response-guided treatment duration (RGT)

Route of Administration: Oral

In Vitro Use Guide

The 50% effective concentration for inhibition of HCV subgenomic replicon replication in Huh 5-2 cells (luciferase assay) by DEBIO-025 was 0.27 +/- 0.03 ug/mL and for CsA 2.8 +/- 0.4 ug/mL. The concentration that reduced the growth of exponentially proliferating Huh 5-2 cells by 50% was greater than 27 ug/mL for DEBIO-025 and 12 +/- 6 ug/mL for CsA, resulting in a selectivity index of approximately 900 for DEBIO-025 and 40 for CsA. DEBIO-025, at concentrations of 0.5 and 1 ug/mL, was able to clear cells from their HCV replicon within three to four passages, whereas treatment with CsA at the same concentrations for seven consecutive passages did not result in clearance of the HCV replicon.

Name

Type

Language

ALISPORIVIR

Official Name

English

DEBIO-025

Code

English

CYCLO(L-ALANYL-D-ALANYL-N-METHYL-L-LEUCYL-N-METHYL-L-LEUCYL-N-METHYL-L-VALYL-(2S,3R,4R,6E)-3-HYDROXY-4-METHYL-2-(METHYLAMINO)-6-OCTENOYL-(2S)-2-AMINOBUTANOYL-N-METHYL-D-ALANYL-N-ETHYL-L-VALYL-L-VALYL-N-METHYL-L-LEUCYL)

Common Name

English

ALISPORIVIR [USAN]

Common Name

English

alisporivir [INN]

Common Name

English

Alisporivir [WHO-DD]

Common Name

English

UNIL025

Code

English

UNIL-025

Code

English

(D-MEALA)3-(ETVAL)4-CSA

Common Name

English

DEBIO025

Code

English

DEB-025

Code

English

DEB025

Code

English

Code System Code Type Description

USAN

YY-92