ILOMASTAT

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C20H28N4O4
Molecular Weight	388.4607
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CNC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CC(C)C)CC(=O)NO

InChI

InChIKey=NITYDPDXAAFEIT-DYVFJYSZSA-N

InChI=1S/C20H28N4O4/c1-12(2)8-13(10-18(25)24-28)19(26)23-17(20(27)21-3)9-14-11-22-16-7-5-4-6-15(14)16/h4-7,11-13,17,22,28H,8-10H2,1-3H3,(H,21,27)(H,23,26)(H,24,25)/t13-,17+/m1/s1

HIDE SMILES / InChI

Molecular Formula	C20H28N4O4
Molecular Weight	388.4607
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/1322694 | https://www.ncbi.nlm.nih.gov/pubmed/29088927 | https://www.ncbi.nlm.nih.gov/pubmed/28692737

Ilomastat (also known as galardin or GM 6001) is a broad-spectrum matrix metalloproteinase inhibitor. It is a member of the hydroxamic acid class of reversible metallopeptidase inhibitors. The hydroxamic acid binds the catalytic zinc(2+) ion in a bidentate manner, blocking substrate access to the active site and rendering the metal incapable of peptide hydrolysis. Preclinical studies have shown that ilomastat can inhibit conjunctival scarring after glaucoma filtration surgery in rabbits, in lens capsules following simulated cataract surgery, and in models of vitreoretinal contraction.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Matrix metalloproteinase-1 8 Target ID: CHEMBL332 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17623656	Inhibitor 8297	3.3 nM [IC50]
Matrix metalloproteinase-2 13 Target ID: CHEMBL333 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17623656	Inhibitor 8297	10.0 nM [IC50]
Matrix metalloproteinase 3 13 Target ID: CHEMBL283 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17623656	Inhibitor 8297	7.0 nM [IC50]
Matrix metalloproteinase 7 3 Target ID: CHEMBL4073 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17623656	Inhibitor 8297	33.0 nM [IC50]
Matrix metalloproteinase 8 6 Target ID: CHEMBL4588 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17623656	Inhibitor 8297	9.7 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Unknown 2578

PubMed

Title	Date	PubMed
Epidermal growth factor receptor-dependent and -independent pathways in hydrogen peroxide-induced mitogen-activated protein kinase activation in cardiomyocytes and heart fibroblasts.	2005 Mar	15574683
Selective inhibition of TNF-alpha-induced activation of mitogen-activated protein kinases and metastatic activities by gefitinib.	2005 May 9	15841081
Shedding of the amyloid precursor protein-like protein APLP2 by disintegrin-metalloproteinases.	2005 Nov	16279945
Differential modulation of Alzheimer's disease amyloid beta-peptide accumulation by diverse classes of metal ligands.	2007 Nov 1	17680773
Acrolein-activated matrix metalloproteinase 9 contributes to persistent mucin production.	2008 Apr	18006877
Expression profiles of matrix metalloproteinase 9 in teleost fish provide evidence for its active role in initiation and resolution of inflammation.	2008 Dec	18557954
Matrix metalloproteinase-14 mediates a phenotypic shift in the airways to increase mucin production.	2009 Nov 1	19661247
Proteolysis controls endogenous substance P levels.	2013	23894327
Characterisation of acetylcholinesterase release from neuronal cells.	2013 Mar 25	23047022
Amyloid-β-induced matrix metalloproteinase-9 secretion is associated with retinal pigment epithelial barrier disruption.	2013 May	23525277
Action of hexachlorobenzene on tumor growth and metastasis in different experimental models.	2013 May 1	23462309

Patents

Sample Use Guides

In Vivo Use Guide

Rabbits received 0.1 mL of 100 uM ilomastat.

Route of Administration: Other

In Vitro Use Guide

Ilomastat inhibits human skin fibroblast collagenase with Ki of 0.4 nM when assayed with a synthetic thioester substrate at pH 6.5, with 50-fold selectivity over two bacterial enzymes, thermolysin, and Pseudomonas aeruginosa elastase.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 17:02:32 GMT 2023` Edited by `admin` on `Sat Dec 16 17:02:32 GMT 2023`
Record UNII	I0403ML141
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ILOMASTAT

Official Name

English

(R)-N(SUP 1)-HYDROXY-N-((S)-2-INDOL-3-YL-1-(METHYLCARBAMOYL)ETHYL)-2-ISOBUTYLSUCCINAMIDE

Systematic Name

English

ilomastat [INN]

Common Name

English

GALARDIN

Common Name

English

GM6001

Code

English

ILOMASTAT [USAN]

Common Name

English

ILOMASTAT [INCI]

Common Name

English

(S-(R*,S*))-N(SUP 4)-HYDROXY-N(SUP 1)-(1H-INDOL-3-YLMETHYL)-2-(METHYLAMINO)-2-OXOETHYL)-2-(2-METHYLOPROPYL)BUTANEDIAMIDE

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

63991