ICOMUCRET

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C20H32O3
Molecular Weight	320.4663
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	4
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCCCC[C@H](O)\C=C\C=C/C\C=C/C\C=C/CCCC(O)=O

InChI

InChIKey=JSFATNQSLKRBCI-VAEKSGALSA-N

InChI=1S/C20H32O3/c1-2-3-13-16-19(21)17-14-11-9-7-5-4-6-8-10-12-15-18-20(22)23/h4-5,8-11,14,17,19,21H,2-3,6-7,12-13,15-16,18H2,1H3,(H,22,23)/b5-4-,10-8-,11-9-,17-14+/t19-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C20H32O3
Molecular Weight	320.4663
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	4
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/12410044
Curator's Comment: The description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/4451568 | http://adisinsight.springer.com/drugs/800019901 | https://goo.gl/7qS2im | https://www.ncbi.nlm.nih.gov/pubmed/12613928 | https://www.ncbi.nlm.nih.gov/pubmed/12613928

Icomucret (15(S)-HETE) is an hydroxyeicosatetraenoic acid developed by Alcon Research, Ltd for treatment Ophthalmic Disorders. In vitro Icomucret has been shown to inhibit LTB4 formation, 12-HETE formation and specifically inhibits the neutrophil chemotactic effect of LTB4. The inhibition of LTB4 formation is probably due to modulation of the 5- lipoxygenase (LO) because no changes in PGE2 formation have been determined. In vivo, Icomucret inhibits LTB4-induced erythema and edema, and reduces LTB4 in the synovial fluid of carragheenan-induced experimental arthritis in dogs. Icomucret has also some immunomodulatory effects. It inhibits the mixed lymphocyte reaction, induces generation of murine cytotoxic suppressor T cells, and it decreases interferon production by murine lymphoma cells. Furthermore, IL-4 and IL-13 have recently been shown to be potent activators of the 15-LO in mononuclear cells. Icomucret induces the secretion of membrane-bound mucins from human conjunctival and corneal epithelial cells. Icomucret was evaluated in clinical trials for Dry Eye Syndrome treatment. However from 2007 no future development reported, and Icomucret development sims to be discontinued.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Mucin-1 secretion 2 Target ID: Mucin-1 secretion Sources: https://www.ncbi.nlm.nih.gov/pubmed/12410044	Activator 1430		1.0 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Dry eye syndrome 21 Sources: http://pubs.acs.org/doi/abs/10.1021/op100244n	Primary		Phase III 656	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Hydroxyeicosanoids bind to and activate the low affinity leukotriene B4 receptor, BLT2.	2001 Apr 13	11278893
12(S)-Hydroxyheptadeca-5Z, 8E, 10E-trienoic acid is a natural ligand for leukotriene B4 receptor 2.	2008 Apr 14	18378794

Patents

Sample Use Guides

In Vivo Use Guide

500 nM in BSS (balanced salt solution) vehicle applied topically to the eye immediately prior to a 2 hour desiccation period.

Route of Administration: Topical

In Vitro Use Guide

Segments of human bulbar conjunctival tissue were incubated with Icomucret (1-1000 nM) for 30 minutes at 37 degrees C. Secretion of human ocular mucins MUC1, MUC2, MUC4, and MUC5AC into the incubation media was measured by dot-blot immunoassay using antibodies directed to unique mucin polypeptide epitopes. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting were used to verify the specificity of anti-mucin antibody binding and to investigate the presence of MUC1 mucin in human tears. Icomucret (10^(-8)-10^(-6) M) stimulated secretion of conjunctival mucins in a concentration-dependent manner. Significant increases in total mucin secretion were observed at 10^(-7) M Icomucret with a maximum response (>50% increase above controls) at 10^(-6) M. Results of immunoassays showed that Icomucret differentially stimulates secretion of MUC1 mucin with no detectable effects on MUC2, MUC4, or MUC5AC release.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:19:29 UTC 2023` Edited by `admin` on `Fri Dec 15 16:19:29 UTC 2023`
Record UNII	44JHK6G39Q
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ICOMUCRET

Official Name

English

5,8,11,13-EICOSATETRAENOIC ACID, 15-HYDROXY-, (5Z,8Z,11Z,13E,15S)-

Common Name

English

ICOMUCRET [USAN]

Common Name

English

AL-12959

Code

English

icomucret [INN]

Common Name

English

(5Z,8Z,11Z,13E,15S)-15-Hydroxyicosa-5,8,11,13-tetraenoic acid

Systematic Name

English

15(S)-HETE

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C78283