Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C22H36N2O6 |
| Molecular Weight | 424.531 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 7 / 7 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
[H][C@@]1([C@H](OC)[C@@H](CC[C@]12CO2)OC(=O)N[C@H](C(C)C)C(N)=O)[C@@]3(C)O[C@@H]3CC=C(C)C
InChI
InChIKey=QBDVVYNLLXGUGN-XGTBZJOHSA-N
InChI=1S/C22H36N2O6/c1-12(2)7-8-15-21(5,30-15)18-17(27-6)14(9-10-22(18)11-28-22)29-20(26)24-16(13(3)4)19(23)25/h7,13-18H,8-11H2,1-6H3,(H2,23,25)(H,24,26)/t14-,15-,16-,17-,18-,21+,22+/m1/s1
PPI-2458 is a synthetic derivative of fumagillin with antineoplastic and cytotoxic properties. PPI-2458 irreversibly inhibits the enzyme methionine aminopeptidase type 2 (MetAP2), thereby preventing abnormal cell growth and angiogenesis. PPI-2458 is reported to have a better toxicity profile compared to other agents of its class. In a phase 1 clinical study, PPI-2458 was administered to patients with non-Hodgkin lymphoma. The data confirm the participation of active metabolites in the in vivo efficacy of PPI-2458. In in vitro studies, osteoclast formation and activity were inhibited by PPI-2458, a mechanism not previously attributed to MetAP-2 inhibition. PPI-2458 treatment reduced synovial and osteochondral angiogenesis, synovial inflammation, joint damage, and pain behavior. PPI-2458 exerts disease-modifying activity in experimental arthritis through its direct inhibition of several pathophysiologic processes of this disease. These results provide a rationale for assessing the potential of PPI-2458 as a novel rheumatoid arthritis therapy.
Originator
Approval Year
PubMed
| Title | Date | PubMed |
|---|---|---|
| Inhibition of melanoma tumor growth by a pharmacological inhibitor of MetAP-2, PPI-2458. | 2006 Apr |
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| A novel methionine aminopeptidase-2 inhibitor, PPI-2458, inhibits non-Hodgkin's lymphoma cell proliferation in vitro and in vivo. | 2006 Apr 15 |
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| Suppression of inflammation and structural damage in experimental arthritis through molecular targeted therapy with PPI-2458. | 2007 Mar |
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| An inhibitor of methionine aminopeptidase type-2, PPI-2458, ameliorates the pathophysiological disease processes of rheumatoid arthritis. | 2008 Jan |
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| Carbamate analogues of fumagillin as potent, targeted inhibitors of methionine aminopeptidase-2. | 2009 Dec 24 |
Patents
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NCI_THESAURUS |
C2143
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NA0Y2SRR29
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431077-35-9
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DTXSID50962902
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6918653
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C38129
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DB05864
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SUBSTANCE RECORD
