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http://linked.open...gbank/description
| - PPI-2458 represents a potentially new and important addition to the growing list of therapeutics aimed at specific molecular oncology targets. PPI-2458 is a novel, proprietary molecule belonging to the fumagillin class of compounds that specifically targets the MetAP-2 enzyme. This class of compounds has been shown to prevent both abnormal cell growth and the formation of new blood vessels (known as angiogenesis), which contribute to the growth of aberrant tissues in diseases such as cancer and rheumatoid arthritis. Clinical development with previous fumagillin derivatives has been limited by their toxicity profile. In preclinical studies to date, PPI-2458 has demonstrated the potent pharmacologic activity of this class of compounds while displaying an improved pharmacokinetic and toxicity profile. (en)
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http://linked.open...generalReferences
| - # Lazarus DD, Doyle EG, Bernier SG, Rogers AB, Labenski MT, Wakefield JD, Karp RM, Clark EJ, Lorusso J, Hoyt JG, Thompson CD, Hannig G, Westlin WF: An inhibitor of methionine aminopeptidase type-2, PPI-2458, ameliorates the pathophysiological disease processes of rheumatoid arthritis. Inflamm Res. 2008 Jan;57(1):18-27. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/18209961 # Cooper AC, Karp RM, Clark EJ, Taghizadeh NR, Hoyt JG, Labenski MT, Murray MJ, Hannig G, Westlin WF, Thompson CD: A novel methionine aminopeptidase-2 inhibitor, PPI-2458, inhibits non-Hodgkin's lymphoma cell proliferation in vitro and in vivo. Clin Cancer Res. 2006 Apr 15;12(8):2583-90. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/16638869 # Hannig G, Lazarus DD, Bernier SG, Karp RM, Lorusso J, Qiu D, Labenski MT, Wakefield JD, Thompson CD, Westlin WF: Inhibition of melanoma tumor growth by a pharmacological inhibitor of MetAP-2, PPI-2458. Int J Oncol. 2006 Apr;28(4):955-63. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/16525646 (en)
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http://linked.open...gy/drugbank/group
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http://linked.open...ugbank/indication
| - Investigated for use/treatment in lymphoma (non-hodgkin's) and solid tumors. (en)
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http://linked.open...mechanismOfAction
| - PPI-2458's potent inhibition of MetAP-2 presents the potential for use as a new therapy for non-Hodgkin's lymphoma (NHL). MetAP-2 is highly expressed in human germinal center B cells. The neoplastic counterparts of these cells are the cell types observed in certain NHL subtypes, such as diffuse large B cell lymphoma and follicular lymphoma. PPI-2458 has been shown to reduce the formation of germinal centers in lymphoid tissues in vivo, have direct anti-proliferative activity on NHL cells in vitro and inhibit the growth of NHL tumors in a preclinical model in vivo. The anti-tumor activity of PPI-2458 was dose-dependent in this preclinical in vivo model and directly correlated with the level of molecular target MetAP-2 enzyme inhibition in tumor tissue, as measured by a proprietary, pharmacodynamic assay developed by PRAECIS. Additionally, the activity of PPI-2458 in this preclinical model was synergistic with several chemotherapeutic agents that are routinely used in combination in NHL patients. (en)
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http://linked.open...ugbank/IUPAC-Name
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http://linked.open...gy/drugbank/InChI
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http://linked.open...Molecular-Formula
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http://linked.open.../Molecular-Weight
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http://linked.open...noisotopic-Weight
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http://linked.open...y/drugbank/SMILES
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http://linked.open.../Water-Solubility
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http://linked.open...ogy/drugbank/logP
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http://linked.open...ogy/drugbank/logS
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http://linked.open...nd-Acceptor-Count
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http://linked.open...-Bond-Donor-Count
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http://linked.open...drugbank/InChIKey
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http://linked.open...urface-Area--PSA-
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http://linked.open...nk/Polarizability
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http://linked.open...bank/Refractivity
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http://linked.open...atable-Bond-Count
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http://linked.open...k/Bioavailability
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http://linked.open...bank/Ghose-Filter
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http://linked.open...nk/MDDR-Like-Rule
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http://linked.open...k/Number-of-Rings
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http://linked.open...siological-Charge
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http://linked.open...bank/Rule-of-Five
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http://linked.open...tional-IUPAC-Name
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http://linked.open...strongest-acidic-
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http://linked.open...-strongest-basic-
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