GM 6001

Names

[ Name ]:
GM 6001

[Synonym ]:
Ilomastat
(2R)-N'-hydroxy-N-[(2S)-3-(1H-indol-3-yl)-1-(methylamino)-1-oxopropan-2-yl]-2-(2-methylpropyl)butanediamide
(S-(R*,S*))-N4-Hydroxy-N{1}-(1-(1H-indol-3-ylmethyl)-2-(methylamino)-2-oxoethyl)-2-(2-methylpropyl)butanediamide
GM6001
(2R)-N4-(hydroxy)-N1-((1S)-1-(1H-indol-3-ylmethyl)-2-(methylamino)-2-oxoethyl)-2-(2-methylpropyl)butanediamide
Butanediamide, N-hydroxy-N-[(1S)-1-(1H-indol-3-ylmethyl)-2-(methylamino)-2-oxoethyl]-2-(2-methylpropyl)-, (2R)-
(2R)-N-Hydroxy-N-[(2S)-3-(1H-indol-3-yl)-1-(methylamino)-1-oxopropan-2-yl]-2-isobutylsuccinamide
(2R)-N-Hydroxy-N-[(2S)-3-(1H-indol-3-yl)-1-(methylamino)-1-oxo-2-propanyl]-2-isobutylsuccinamide
Galardin

Biological Activity

[Description]:

Ilomastat (Galardin; GM6001) is a broad spectrum matrix metalloprotease (MMP) inhibitor, with Ki of 0.4 nM, 0.5 nM, 27 nM, 3.7 nM, 0.1 nM, 0.2 nM, 3.6 nM, 13.4 nM, 0.36 nM for MMP-1/2/3/7/8/9/12/14/26, respectively.

[Related Catalog]:

Signaling Pathways >> Metabolic Enzyme/Protease >> MMP

Research Areas >> Cancer

[Target]

Ki: 0.4 nM (MMP-1), 0.5 nM (MMP-2), 27 nM (MMP-3), 3.7 nM (MMP-7), 0.1 nM (MMP-8), 0.2 nM (MMP-9), 3.6 nM (MMP-12), 13.4 nM (MMP-14), 0.36 nM (MMP-26)

[In Vitro]

Ilomastat (GM6001) inhibits human skin fibroblast collagenase with Ki of 0.4 nM when assayed with a synthetic thio ester substrate at pH 6.5, with 50-fold selectivity over two bacterial enzymes, thermolysin and Pseudomonas aeruginosa elastase[1]. Ilomastat (0.1 nM-10 nM) inhibits gelatinase A and gelatinase B produced by T-cells, and thus inhibits T-cell homing[4].

[In Vivo]

Ilomastat (GM6001) (400 μg/mL) prevents corneal ulceration after severe alkali injury[2]. Ilomastat (GM6001) significantly inhibits intimal hyperplasia and intimalcollagen content, and it increases lumen area in stented arteries without effects on proliferation rates in rabbit model after stenting[3].

[Animal admin]

To assess the effects of MMP inhibition, animals are given daily injections of either vehicle (“placebo group”) or Ilomastat (GM6001) (100 mg/kg per day as subcutaneous suspension), beginning one day before the second injury until seven days after the procedure. Ilomastat (GM6001) is a nonspecific hydroxamic acid-based MMPI with potent inhibitory activity against collagenase, gelatinases and stromelysin. Animals are euthanized at either 1 week or 10 weeks after the second injury. For biochemical studies, iliac artery tissue is removed under general anesthetic, followed by a fatal intracardiac injection of thiopentol. For histomorphometric studies, iliac arteries are perfusion-fixed in 10% buffered formalin for 20 min at a perfusion pressure of 80 mm Hg.

[References]

[1]. Grobelny D, et al. Inhibition of human skin fibroblast collagenase, thermolysin, and Pseudomonas aeruginosa elastase by peptide hydroxamic acids. Biochemistry. 1992 Aug 11;31(31):7152-4.

[2]. Schultz GS, et al. Treatment of alkali-injured rabbit corneas with a synthetic inhibitor of matrix metalloproteinases. Invest Ophthalmol Vis Sci. 1992 Nov;33(12):3325-31.

[3]. Li C, et al. Arterial repair after stenting and the effects of GM6001, a matrix metalloproteinase inhibitor. J Am Coll Cardiol. 2002 Jun 5;39(11):1852-8.

[4]. Leppert D, et al. T cell gelatinases mediate basement membrane transmigration in vitro. J Immunol. 1995 May 1;154(9):4379-89.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.228±0.06 g/cm3

[ Molecular Formula ]:
C₂₀H₂₈N₄O₄

[ Molecular Weight ]:
388.461

[ Exact Mass ]:
388.211060

[ PSA ]:
123.32000

[ LogP ]:
0.83

[ Appearance of Characters ]:
Off-white solid

[ Index of Refraction ]:
1.590

[ Storage condition ]:
2-8°C

[ Water Solubility ]:
Practically insoluble (0.062 g/L) (25 ºC)

MSDS

Click to get detail MSDS

Safety Information

[ Personal Protective Equipment ]:
Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter

[ Safety Phrases ]:
22-24/25

[ RIDADR ]:
NONH for all modes of transport

[ WGK Germany ]:
3

[ HS Code ]:
29339900

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Articles

Inhibition of human skin fibroblast collagenase, thermolysin, and Pseudomonas aeruginosa elastase by peptide hydroxamic acids.

Biochemistry 31 , 7152, (1992)

The hydroxamic acid HONHCOCH2CH(i-Bu)CO-L-Trp-NHMe, isomer 6A (GM 6001), inhibits human skin fibroblast collagenase with Ki of 0.4 nM using the synthetic thiol ester substrate Ac-Pro-Leu-Gly-SCH(i-Bu)...