Ilomastat - CAS 142880-36-2
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Not Intended for Therapeutic Use. For research use only.
Ilomastat, also known as GM6001 and galardin, is a broad-spectrum matrix metalloproteinase inhibitor with potential anticancer activity. 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. Examples of enzymes that ilomastat inhibit include thermolysin, peptide deformylase, and anthrax lethal factor endopeptidase (LF) produced by the bacterium Bacillus anthracis.
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white solid powder
Ilomastat, GM6001; GM-6001; GM 6001; galardin
1.Sequential Therapy with Saratin, Bevacizumab and Ilomastat to Prolong Bleb Function following Glaucoma Filtration Surgery in a Rabbit Model.
Martorana GM1, Schaefer JL1, Levine MA1, Lukowski ZL1, Min J1, Meyers CA1, Schultz GS2, Sherwood MB1. PLoS One. 2015 Sep 22;10(9):e0138054. doi: 10.1371/journal.pone.0138054. eCollection 2015.
To determine if sequential treatment with Bevacizumab (Avastin), a monoclonal, VEGF antibody that blocks angiogenesis; Saratin, a 12 kD polypeptide with anti-inflammatory and anti-thrombotic properties; and Ilomastat, a matrix metalloproteinase (MMP) inhibitor, prolongs bleb life following glaucoma filtration surgery (GFS) in a rabbit model. Thirty-two New Zealand White rabbits (eight rabbits per group) underwent GFS in the left eye. Group 1 received a perioperative injection of both Saratin and Bevacizumab, and later, subconjuctival injections of Ilomastat on days 8 and 15. Group 2 received only Saratin perioperatively, and also received Ilomastat injections on days 8 and 15. Group 3, the negative control, received a single perioperative injection of Balanced Saline Solution (BSS) along with post-operative BSS injections on days 8 and 15. Group 4, the positive control, received topical treatment with Mitomycin-C (MMC) at the time of surgery with no further treatment.
2.Selective non-zinc binding MMP-2 inhibitors: Novel benzamide Ilomastat analogs with anti-tumor metastasis.
Song J1, Peng P1, Chang J1, Liu MM2, Yu JM1, Zhou L3, Sun X4. Bioorg Med Chem Lett. 2016 May 1;26(9):2174-8. doi: 10.1016/j.bmcl.2016.03.064. Epub 2016 Mar 16.
Novel Ilomastat analogs with substituted benzamide groups, instead of hydroxamic acid groups, were designed, synthesized and evaluated against MMP-2 and MMP-9. Among these analogs, the most potent compound 10a exhibited potent inhibitory activity against MMP-2 with IC50 value of 0.19nM, which is 5 times more potent than that of Ilomastat (IC50=0.94nM). Importantly, 10a exhibited more than 8300 fold selectivity for MMP-2 versus MMP-9 (IC50=1.58μM). Molecular docking studies showed that 10a bond to the catalytic active pocket of MMP-2 by a non-zinc-chelating mechanism which was different from that of Ilomastat. Furthermore, the invasion assay showed that 10a was effective in reducing HEY cells invasion at 84.6% in 50μM concentration. For 10a, the pharmacokinetic properties had been improved and especially the more desirable t1/2z was achieved compared with these of the lead compound Ilomastat.
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