GM6001

GM6001

Names
IUPAC name (2R)-N'-hydroxy-N-[(2S)-3-(5H-indol-3-yl)-1-methylamino-1-oxopropan-2-yl]-2-(2-methylpropyl)butanediamide
Other names galardin, ilomastat
Identifiers
CAS Number	142880-36-2
Abbreviations	GM6
ChemSpider	117009
DrugBank	DB02255
Jmol interactive 3D	Image
MeSH	GM6001
PubChem	5288446
InChI 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/h5-7,11-13,17,28H,4,8-10H2,1-3H3,(H,21, 27)(H,23,26)(H,24,25)/t13-,17+/m1/s1
SMILES CC(C)C[C@H](CC(=O)NO)C(=O)N[C@@H](CC1=CN=C2C1=CCC=C2)C(=O)NC
Properties
Chemical formula	C20H27N4O4
Molar mass	387.46 g·mol^−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

GM6001 also known as galardin or ilomastat is a broad-spectrum matrix metalloproteinase inhibitor.^[1][2][3]

GM6001 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.^[4]

Examples of enzymes that ilomastat inhibit include thermolysin,^[1] peptide deformylase,^[5] and anthrax lethal factor endopeptidase (LF) produced by the bacterium Bacillus anthracis.^[6][7]

References

1. 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.
2. 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.
3. 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.
4. "Small-molecule inhibitor J16.402: galardin". MEROPS - the Peptidase Database. Wellcome Trust Sanger Institute. 2010-09-07. Retrieved 2010-10-04.
5. 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.
6. 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.
7. 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.