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

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
Tamoxifen induces apoptosis in Fas+ tumor cells by upregulating the expression of Fas ligand.	2003 Apr	12721755
Heparin-binding epidermal growth factor cleavage mediates zinc-induced epidermal growth factor receptor phosphorylation.	2004 Apr	12972402
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
Methylmercury induces activation of Notch signaling.	2006 Dec	16757030
Effects of alpha1D-adrenergic receptors on shedding of biologically active EGF in freshly isolated lacrimal gland epithelial cells.	2006 Nov	16760267
Discovery and characterization of a novel inhibitor of matrix metalloprotease-13 that reduces cartilage damage in vivo without joint fibroplasia side effects.	2007 Sep 21	17623656
Acrolein-activated matrix metalloproteinase 9 contributes to persistent mucin production.	2008 Apr	18006877
Fluoxetine-mediated 5-HT2B receptor stimulation in astrocytes causes EGF receptor transactivation and ERK phosphorylation.	2008 Dec	18758753
Expression profiles of matrix metalloproteinase 9 in teleost fish provide evidence for its active role in initiation and resolution of inflammation.	2008 Dec	18557954
Beta-blockers alprenolol and carvedilol stimulate beta-arrestin-mediated EGFR transactivation.	2008 Sep 23	18787115
Evaluation of protease inhibitors and an antioxidant for treatment of sulfur mustard-induced toxic lung injury.	2009 Sep 1	18852015
Ovarian steroids, mitogen-activated protein kinases, and/or aspartic proteinases cooperate to control endometrial remodeling by regulating gene expression in the stroma and glands.	2010 Sep	20660070
Cocarcinogenic effect of capsaicin involves activation of EGFR signaling but not TRPV1.	2010 Sep 1	20660715
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.

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