142880-36-2

Basic information

• Product Name: Ilomastat
• Synonyms: (2R)-N4-Hydroxy-N1-[(1S)-1-(1H-indol-3-ylmethyl)-2-(methylamino)-2-oxoethyl]-2-(2-methylpropyl)-butanediamide Ilomastat (GM6001, Galardin);Galardin CS 610;Ilomastat, >=98%;(R)-N1-((S)-3-(1H-Indol-3-yl)-1-(methylamino)-1-oxopropan-2-yl)-N4-hydroxy-2-isobutylsuccinami;(r)-n4-hydroxy-n1-[(s)-2-(1h-indol-3-yl)-1-methylcarbamoly-ethyl]-2-isobutyl-succinamide;galardin tm;(R)-N4-Hydroxy-N1-[(S)-2-(1H-indol-3-yl)-1-methylcarbamoyl-ethyl]-2-isobutyl-succinamide;Galardin, GM6001, Ilomastat
• CAS NO: 142880-36-2
• Molecular Formula: C₂₀H₂₈N₄O₄
• Molecular Weight: 388.47
• Product Categories: Inhibitors
• Mol File: 142880-36-2.mol

Chemical Properties

• Boiling Point: °Cat760mmHg
• Flash Point: °C
• Appearance: /
• Density: 1.228g/cm³
• Refractive Index: 1.589
• Storage Temp.: 2-8°C
• Solubility: Soluble in DMSO, and 100% ethanol.
• PKA: 9.16±0.20(Predicted)
• Sensitive: Moisture Sensitive
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 3 months.
• CAS DataBase Reference: Ilomastat(CAS DataBase Reference)
• NIST Chemistry Reference: Ilomastat(142880-36-2)
• EPA Substance Registry System: Ilomastat(142880-36-2)

Safety Data

• Safety Statements: 22-24/25
• WGK Germany: 3
• Hazardous Substances Data: 142880-36-2(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Ilomastat is used as a metalloprotease inhibitor for the inhibition of various matrix metalloproteinases (MMPs) such as MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-12, MMP-14, and MMP-26. It is particularly effective in inhibiting these enzymes with Ki values ranging from 0.1 nM to 27 nM, making it a potent compound for research and therapeutic applications.
Used in Cancer Research:
Ilomastat is used as an inhibitor of MMPs for cancer research, as these enzymes are often overexpressed in various types of cancer and contribute to tumor growth, invasion, and metastasis. By inhibiting MMPs, Ilomastat may help to slow down or prevent these processes, providing a potential therapeutic approach for cancer treatment.
Used in Inflammation Research:
Ilomastat is used as an inhibitor of MMPs in inflammation research, as these enzymes are involved in the breakdown of extracellular matrix proteins and the regulation of inflammatory responses. By inhibiting MMPs, Ilomastat may help to modulate inflammation and provide insights into the role of these enzymes in various inflammatory diseases.
Used in Tissue Remodeling Research:
Ilomastat is used as an inhibitor of MMPs in tissue remodeling research, as these enzymes play a crucial role in the degradation and turnover of extracellular matrix components. By inhibiting MMPs, Ilomastat may help to study the effects of these enzymes on tissue remodeling and wound healing processes.
Used in Drug Development:
Ilomastat is used as a lead compound in the development of new drugs targeting MMPs for various therapeutic applications, including cancer, inflammation, and tissue remodeling. Its potent and broad-spectrum inhibition of MMPs makes it a valuable starting point for the design and optimization of new MMP inhibitors with improved selectivity, potency, and pharmacokinetic properties.

Biochem/physiol Actions

GM6001 promotes cardiovascular and hepatocellular function.

References

1) Saghatelian et al. (2004) Activity-based probes for the proteomic profiling of metalloproteases; Proc. Natl. Acad. Sci. USA, 101 10000 2) Galardy et al. (1994) Low molecular weight inhibitors in corneal ulceration; Ann. N.Y. Acad..Sci. 732 315 3) Yamamoto et al.(1998) Inhibition of Membrane-Type 1 Matrix Metalloproteinase by Hydroxamate Inhibitors: An Examination of the Subsite Pocket; J. Med. Chem. 41 1209 4) Park et al. (2003) The intermediate S1- pocket of the endometase/matrilysin-2 active site revealed by enzyme inhibition kinetic studies, protein sequence analyses, and homology modeling; J. Biol. Chem. 278 51646

InChI:InChI=1/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

Upstream product

• 171347-91-4 (R)-5-Methyl-3-((S)-1-phenyl-ethylcarbamoyl)-hexanoic acid methyl ester 
• 162678-79-7 (2R)-2-[(methoxycarbonyl)methyl]-4-methylpentanoic acid 
• 14035-83-7 dihydro-3-(RS)-(2-methylpropyl)-2,5-furandione 
• 132631-36-8 D,L-2-isobutyl-3-(methoxycarbonyl)-propanoic acid 
• 13139-14-5 Boc-Trp-OH 
• 122900-21-4 N^α-Boc-L-tryptophan N-methylamide 
• 18908-20-8 2-methyl-2-propen-1-yl succinic anhydride 
• 53708-63-7 (S)-2-amino-3-(1H-indol-3-yl)-N-methylpropanamide 
• 171347-80-1 (R)-N⁴-Benzyloxy-N¹-[(S)-2-(1H-indol-3-yl)-1-methylcarbamoyl-ethyl]-2-isobutyl-succinamide 
• 142880-34-0 (R)-3-[(S)-2-(1H-Indol-3-yl)-1-methylcarbamoyl-ethylcarbamoyl]-5-methyl-hexanoic acid methyl ester 

Downstream Products

• 171347-80-1 (R)-N⁴-Benzyloxy-N¹-[(S)-2-(1H-indol-3-yl)-1-methylcarbamoyl-ethyl]-2-isobutyl-succinamide 

Relevant articles and documents

USE OF SUBSTITUTED 2 PHENYLBENZIMIDAZOLES AS MEDICAMENTS

The present invention relates to the use of a substituted 2-phenylbenzimidazole of formula I wherein R1, R2, R3, R 4, R5 and m have the meanings given in the claims, for the preparation of a medicament for the treatment or prevention of diseases involving glucagon receptors, as well as new compounds of formula I wherein R1 is a group of formula

Inhibition of membrane-type 1 matrix metalloproteinase by hydroxamate inhibitors: An examination of the subsite pocket

The membrane-type 1 matrix metalloproteinase (MT1-MMP) has been reported to mediate the activation of pro-gelatinase A (proMMP-2), which is associated with tumor proliferation and metastasis. MT1-MMP can also digest extracellular matrix (ECM) such as interstitial collagens, gelatin, and proteoglycan and thus may play an important role in pathophysiological digestion of ECM. We studied the inhibitory effect of various hydroxamate MMP inhibitors, including known inhibitors such as BB-94, BB-2516, GM6001, and Ro31-9790, on a deletion mutant of MT1-MMP lacking the transmembrane domain (ΔMT1) to further characterize the enzyme and develop a selective inhibitor for MT1-MMP. The evaluation of the inhibitory activities of various hydroxamates reveals general structural profiles affecting selectivities toward MMPs. In particular, a longer side chain at the P1' position is preferable for the binding to MMP-2, -3, and -9 and MT1-MMP. For the P2' position, an α-branched alkyl group is critical for the binding toward ΔMT1, while the introduction of a bulky group at the α-position of hydroxamic acid seems to diminish the activity against ΔMT1. Summation of the data on the sensitivity of ΔMT1 to various hydroxamate inhibitors indicates that (1) the volume of the S1' subsite of ΔMT1 is similar to that of MMP-2, -3, and -9, which is bigger than that of MMP-1, and (2) the S1 and S2' subsites are narrower than those in other MMPs. On the basis of these results, the hydroxamates with a P1' phenylpropyl and P2' α-branched alkyl group were synthesized and evaluated for inhibitory activity. These inhibitors (1h,i) showed strong activity against ΔMT1 over MMP-1, but no selectivity between ΔMT1 and MMP-9. These results are explained using molecular modeling studies conducted on MT1-MMP.

Matrix metalloproteinase inhibitors: A structure-activity study

Modifications around the dipeptide-mimetic core of a hydroxamic acid based matrix metalloproteinase inhibitor were studied. These variations incorporated a variety of natural, unnatural, and synthetic amino acids inaddition to modifications of the P1' and P3' substituents. The results of this study indicate the following structural requirements: (2) Potent inhibitorsmust possess string zinc-binding functionalities. (3) The potential importance of the hydrophobic group at position R3 as illustratedby itsability to impart greater relative potency against stromelysin when larger hydrophobic groups are used. (4) Requirements surrounding the nature of the amino acid appear to be more restrictive for stromelysin than for neutrophil collagenase, 72 kDa gelatinase, and 92 kDa gelatinase. These requirements may involve planar fused-ring aryl systems and possibly hydrogen-bonding capabilities.