PPI-2458

    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 202330

CAS#: 431077-35-9

Description: 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.


Chemical Structure

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PPI-2458
CAS# 431077-35-9

Theoretical Analysis

MedKoo Cat#: 202330
Name: PPI-2458
CAS#: 431077-35-9
Chemical Formula: C22H36N2O6
Exact Mass: 424.25734
Molecular Weight: 424.53
Elemental Analysis: C, 62.24; H, 8.55; N, 6.60; O, 22.61

Price and Availability

This product is not in stock, which may be available by custom synthesis. For cost-effective reason, minimum order is 1g (price is usually high, lead time is 2~3 months, depending on the technical challenge). Quote less than 1g will not be provided. To request quote, please email to sales @medkoo.com or click below button.
Note: Price will be listed if it is available in the future.

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Synonym: PPI 2458; PPI-2458; PPI2458.

IUPAC/Chemical Name: (3R,4S,5S,6R)-5-methoxy-4-((2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl)-1-oxaspiro[2.5]octan-6-yl ((R)-1-amino-3-methyl-1-oxobutan-2-yl)carbamate

InChi Key: QBDVVYNLLXGUGN-XGTBZJOHSA-N

InChi Code: 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

SMILES Code: O=C(O[C@H](CC1)[C@@H](OC)[C@H]([C@@]2(C)O[C@@H]2C/C=C(C)\C)[C@]31CO3)N[C@H](C(C)C)C(N)=O

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >5 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Preparing Stock Solutions

The following data is based on the product molecular weight 424.53 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL

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 1: Arico-Muendel CC, Belanger B, Benjamin D, Blanchette HS, Caiazzo TM, Centrella PA, DeLorey J, Doyle EG, Gradhand U, Griffin ST, Hill S, Labenski MT, Morgan BA, O'Donovan G, Prasad K, Skinner S, Taghizadeh N, Thompson CD, Wakefield J, Westlin W, White KF. Metabolites of PPI-2458, a selective, irreversible inhibitor of methionine aminopeptidase-2: structure determination and in vivo activity. Drug Metab Dispos. 2013 Apr;41(4):814-26. doi: 10.1124/dmd.112.048355. Epub 2013 Jan 25. PubMed PMID: 23355637.

2: Brahn E, Schoettler N, Lee S, Banquerigo ML. Involution of collagen-induced arthritis with an angiogenesis inhibitor, PPI-2458. J Pharmacol Exp Ther. 2009 May;329(2):615-24. doi: 10.1124/jpet.108.148478. Epub 2009 Feb 13. PubMed PMID: 19218530; PubMed Central PMCID: PMC2672877.

3: 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. doi: 10.1007/s00011-007-7075-5. PubMed PMID: 18209961.

4: Hannig G, Bernier SG, Hoyt JG, Doyle B, Clark E, Karp RM, Lorusso J, Westlin WF. Suppression of inflammation and structural damage in experimental arthritis through molecular targeted therapy with PPI-2458. Arthritis Rheum. 2007 Mar;56(3):850-60. PubMed PMID: 17328059.

5: 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 PMID: 16638869.

6: 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 PMID: 16525646.

7: Bernier SG, Lazarus DD, Clark E, Doyle B, Labenski MT, Thompson CD, Westlin WF, Hannig G. A methionine aminopeptidase-2 inhibitor, PPI-2458, for the treatment of rheumatoid arthritis. Proc Natl Acad Sci U S A. 2004 Jul 20;101(29):10768-73. Epub 2004 Jul 12. PubMed PMID: 15249666; PubMed Central PMCID: PMC490009.



Additional Information

PPI-2458, a novel, orally active agent of the fumagillin class of irreversible methionine aminopeptidase-2 (MetAP-2) inhibitors, potently inhibited the proliferation of B16F10 melanoma cells in vitro, with a growth inhibitory concentration 50% (GI50) of 0.2 nM. B16F10 growth inhibition was correlated with the inhibition of MetAP-2 enzyme, in a dose-dependent fashion, as determined by a pharmacodynamic assay, which measures the amount of uninhibited MetAP-2 following PPI-2458 treatment.  The antiproliferative activity, coupled with additional observations from studies in vitro (absence of detectable resistance to PPI-2458 and induction of morphological features consistent with differentiated melanocytes), provides a rationale for assessing the therapeutic potential of PPI-2458 in the treatment of melanoma. see http://www.ncbi.nlm.nih.gov/pubmed/16525646.