9-(N-METHYL-L-ISOLEUCINE)-CYCLOSPORIN A

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C62H111N11O12
Molecular Weight	1202.6112
Optical Activity	UNSPECIFIED
Defined Stereocenters	13 / 13
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure of 9-(N-METHYL-L-ISOLEUCINE)-CYCLOSPORIN A

Structure Search

SMILES

CC[C@H](C)[C@@H]1N(C)C(=O)CN(C)C(=O)[C@H](CC)NC(=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](NC1=O)C(C)C

InChI

InChIKey=RPJPZDVUUKWPGT-FOIHOXPVSA-N

InChI=1S/C62H111N11O12/c1-25-28-29-40(15)52(75)51-56(79)65-43(27-3)58(81)67(18)33-47(74)71(22)50(39(14)26-2)55(78)66-48(37(10)11)61(84)68(19)44(30-34(4)5)54(77)63-41(16)53(76)64-42(17)57(80)69(20)45(31-35(6)7)59(82)70(21)46(32-36(8)9)60(83)72(23)49(38(12)13)62(85)73(51)24/h25,28,34-46,48-52,75H,26-27,29-33H2,1-24H3,(H,63,77)(H,64,76)(H,65,79)(H,66,78)/b28-25+/t39-,40+,41-,42+,43-,44-,45-,46-,48-,49-,50-,51-,52+/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/7815548 | https://www.ncbi.nlm.nih.gov/pubmed/12065751 | https://www.ncbi.nlm.nih.gov/pubmed/7884893 | https://adisinsight.springer.com/drugs/800002632 | https://www.ncbi.nlm.nih.gov/pubmed/23202494

9-(N-methyl-L-isoleucine)-cyclosporin A (NIM-811, SDZ 811) is a cyclosporin A analog that is completely devoid of immunosuppressive capacity but exhibits potent and selective anti-human immunodeficiency virus type 1 (HIV-1) activity. NIM-811 interferes at two stages of the viral replication cycle: (i) translocation of the preintegration complex to the nucleus and (ii) production of infectious virus particles. NIM-811 induces a concentration-dependent reduction of HCV RNA in the replicon cells with an IC50 of 0.66 uM at 48 h. NIM-811 blocks the mitochondrial permeability transition induced by calcium and inorganic phosphate. NIM-811 blocks cell killing and prevents in situ mitochondrial inner membrane permeabilization and depolarization during tumor necrosis factor-α–induced apoptosis to cultured rat hepatocytes.Novartis discontinued development of SDZ 811 as an oral therapy for hepatitis C and HIV-1 infections.

Originator

Approval Year

PubMed

Title	Date	PubMed
Cyclophilin inhibitors: an emerging class of therapeutics for the treatment of chronic hepatitis C infection.	2012-10-29	23202494
NIM811, a cyclophilin inhibitor, exhibits potent in vitro activity against hepatitis C virus alone or in combination with alpha interferon.	2006-09	16940091
Inhibition of the mitochondrial permeability transition by the nonimmunosuppressive cyclosporin derivative NIM811.	2002-07	12065751

Sample Use Guides

In Vivo Use Guide

BID in various doses (between 100 mg - 600 mg bid) + SOC (PEG IFN and RBV)

Route of Administration: Oral

In Vitro Use Guide

NIM-811 induces a concentration-dependent reduction of HCV RNA in the replicon cells with an IC50 of 0.66 uM at 48 h. Furthermore, a greater than three-log10 viral RNA reduction is achieved after treating the cells with as little as 1 uM of NIM811 for 9 days.

Name

Type

Language

9-(N-METHYL-L-ISOLEUCINE)-CYCLOSPORIN A

Common Name

English

CYCLOSPORIN A, 9-(N-METHYL-L-ISOLEUCINE)-

Preferred Name

English

NIM-811

Common Name

English

NIM811

Code

English

Code System Code Type Description

PUBCHEM

6473876