Cyclosporin H

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C62H111N11O12
Molecular Weight	1202.6112
Optical Activity	UNSPECIFIED
Defined Stereocenters	12 / 12
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](CC(C)C)N(C)C(=O)CN(C)C1=O)C(C)C

InChI

InChIKey=PMATZTZNYRCHOR-JLPRAAIDSA-N

InChI=1S/C62H111N11O12/c1-25-27-28-40(15)52(75)51-56(79)65-43(26-2)58(81)67(18)33-48(74)68(19)44(29-34(3)4)55(78)66-49(38(11)12)61(84)69(20)45(30-35(5)6)54(77)63-41(16)53(76)64-42(17)57(80)70(21)46(31-36(7)8)59(82)71(22)47(32-37(9)10)60(83)72(23)50(39(13)14)62(85)73(51)24/h25,27,34-47,49-52,75H,26,28-33H2,1-24H3,(H,63,77)(H,64,76)(H,65,79)(H,66,78)/b27-25+/t40-,41+,42-,43+,44+,45+,46+,47+,49+,50-,51+,52-/m1/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/8765829
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/8387097 | http://onlinelibrary.wiley.com/doi/10.1002/hlca.19820650538/abstract | https://www.ncbi.nlm.nih.gov/pubmed/17687636

The ciclosporin analogue ciclosporin H is a potent and selective inhibitor of mediator release from basophils induced by activation of the formyl peptide receptor, and therefore has potential as an anti-inflammatory agent. It acts by interfering with agonist binding to formylmethionylleucylphenylalanine (FMLP) receptors. Unlike ciclosporin [ciclosporin A], ciclosporin H has Dmethyl valine (rather than the Lisomer) at position 11, has an extremely low affinity for cyclophilin, and is devoid of immunosuppressive activity. Ciclosporin H was undergoing preclinical investigation with researchers at the University of Naples Federico II in Italy as an antiinflammatory agent. However, no recent development has been reported.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
fMet-Leu-Phe receptor 1/2 1 Target ID: CHEMBL3038479 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8387097	Antagonist 2849		0.79 µM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Unknown 2596

PubMed

Title	Date	PubMed
Cyclosporin H, Boc-MLF and Boc-FLFLF are antagonists that preferentially inhibit activity triggered through the formyl peptide receptor.	2007-12	17687636
Cyclosporin H is a potent and selective formyl peptide receptor antagonist. Comparison with N-t-butoxycarbonyl-L-phenylalanyl-L-leucyl-L-phenylalanyl-L- leucyl-L-phenylalanine and cyclosporins A, B, C, D, and E.	1993-05-15	8387097

Patents

Sample Use Guides

In Vivo Use Guide

Unknown

Route of Administration: Unknown

In Vitro Use Guide

Ciclosporin H activity was determined in calcium imaging assay. HL-60 cells and HEL cells were incubated for 3 min with or without ciclosporin H before the addition of agonist N-Formyl-Met-Leu-Phe (FMLP). Ciclosporin H inhibited the stimulatory effects of FMLP on cytosolic Ca2+ concentration with Ki values of 0.08 mkM

Name

Type

Language

Cyclosporin H

Common Name

English

SANDOZ-37-839

Preferred Name

English

CYCLOSPORIN A, 5-(N-METHYL-D-VALINE)-

Common Name

English

CYCLOSPORINE H

Common Name

English

CYCLO(L-ALANYL-D-ALANYL-N-METHYL-L-LEUCYL-N-METHYL-L-LEUCYL-N-METHYL-D-VALYL-(3R,4R,6E)-6,7-DIDEHYDRO-3-HYDROXY-N,4-DIMETHYL-L-2-AMINOOCTANOYL-L-2-AMINOBUTANOYL-N-METHYLGLYCYL-N-METHYL-L-LEUCYL-L-VALYL-N-METHYL-L-LEUCYL)

Systematic Name

English

CYCLOSPORIN H, (-)-

Common Name

English

Code System Code Type Description

CAS

83602-39-5