Ilomastat

GM6001
Names
Preferred IUPAC name
(3R)-N1-Hydroxy-N4-{(1S)-1-[(1H-indol-3-yl)methyl]-2-(methylamino)-2-oxoethyl}-3-(2-methylpropyl)butanediamide
Other names
Galardin, GM6001
Identifiers
3D model (JSmol)
Abbreviations GM6
ChEBI
ChemSpider
DrugBank
MeSH GM6001
UNII
  • 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
  • CC(C)C[C@H](CC(=O)NO)C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)NC
Properties
C20H28N4O4
Molar mass 388.468 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Ilomastat (INN),[1] (codenamed GM6001, proprietary name Galardin®) is a broad-spectrum matrix metalloproteinase inhibitor.[2][3][4]

This chemotherapy agent is considered to have application in skincare products for its antiaging properties.

Ilomastat is a member of the hydroxamic acid class of reversible metallopeptidase inhibitors. The anionic state of the hydroxamic acid group forms a bidentate complex with the active site zinc.[5]

Examples of enzymes that ilomastat inhibit include rabbit MMP9,[6] thermolysin,[2] peptide deformylase,[7] and anthrax lethal factor endopeptidase (LF) produced by the bacterium Bacillus anthracis.[8][9]

References

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  1. ^ "International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended International Nonproprietary Names: List 36" (PDF). World Health Organization. p. 148. Retrieved 23 February 2017.
  2. ^ a b Grobelny D, Poncz L, Galardy RE (August 1992). "Inhibition of human skin fibroblast collagenase, thermolysin, and Pseudomonas aeruginosa elastase by peptide hydroxamic acids". Biochemistry. 31 (31): 7152–4. doi:10.1021/bi00146a017. PMID 1322694.
  3. ^ Schultz GS, Strelow S, Stern GA, Chegini N, Grant MB, Galardy RE, Grobelny D, Rowsey JJ, Stonecipher K, Parmley V (November 1992). "Treatment of alkali-injured rabbit corneas with a synthetic inhibitor of matrix metalloproteinases". Invest. Ophthalmol. Vis. Sci. 33 (12): 3325–31. PMID 1385350.
  4. ^ Santiskulvong C, Rozengurt E (November 2003). "Galardin (GM 6001), a broad-spectrum matrix metalloproteinase inhibitor, blocks bombesin- and LPA-induced EGF receptor transactivation and DNA synthesis in rat-1 cells". Exp. Cell Res. 290 (2): 437–46. doi:10.1016/S0014-4827(03)00355-0. PMID 14568001.
  5. ^ "Small-molecule inhibitor J16.402: galardin". MEROPS - the Peptidase Database. Wellcome Trust Sanger Institute. 2010-09-07. Retrieved 2010-10-04.[permanent dead link]
  6. ^ Fini ME, Cui TY, Mouldovan A, Grobelny D, Galardy RE, Fisher SJ (1991). "An inhibitor of the matrix metalloproteinase synthesized by rabbit corneal epithelium". Invest Ophthalmol Vis Sci. 32 (11): 2997–3001. PMID 1655675.
  7. ^ Balakrishnan A, Patel B, Sieber SA, Chen D, Pachikara N, Zhong G, Cravatt BF, Fan H (June 2006). "Metalloprotease inhibitors GM6001 and TAPI-0 inhibit the obligate intracellular human pathogen Chlamydia trachomatis by targeting peptide deformylase of the bacterium". J. Biol. Chem. 281 (24): 16691–9. doi:10.1074/jbc.M513648200. PMID 16565079.
  8. ^ Kocer SS, Walker SG, Zerler B, Golub LM, Simon SR (November 2005). "Metalloproteinase inhibitors, nonantimicrobial chemically modified tetracyclines, and ilomastat block Bacillus anthracis lethal factor activity in viable cells". Infect. Immun. 73 (11): 7548–57. doi:10.1128/IAI.73.11.7548-7557.2005. PMC 1273843. PMID 16239558.
  9. ^ PDB: 1PWU​; Turk BE, Wong TY, Schwarzenbacher R, Jarrell ET, Leppla SH, Collier RJ, Liddington RC, Cantley LC (January 2004). "The structural basis for substrate and inhibitor selectivity of the anthrax lethal factor". Nat. Struct. Mol. Biol. 11 (1): 60–6. doi:10.1038/nsmb708. PMID 14718924. S2CID 39119275.
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