PPI-2458 | CAS#431077-35-9 | MetAP2 inhibitor

MedKoo Cat#: 202330 | Name: PPI-2458

Description:

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

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

PPI-2458

CAS#431077-35-9

Theoretical Analysis

MedKoo Cat#: 202330

Name: PPI-2458

CAS#: 431077-35-9

Chemical Formula: C22H36N2O6

Exact Mass: 424.2573

Molecular Weight: 424.53

Elemental Analysis: C, 62.24; H, 8.55; N, 6.60; O, 22.61

Price and Availability

This product is currently not in stock but may be available through custom synthesis. To ensure cost efficiency, the minimum order quantity is 1 gram. The estimated lead time is 2 to 4 months, with pricing dependent on the complexity of the synthesis (typically high for intricate chemistries). Quotes for quantities below 1 gram will not be provided. To request a quote, please click the button below. Note: If this product becomes available in stock in the future, pricing will be listed accordingly.

Bulk Inquiry

Related CAS #

No Data

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

More Info

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.

Instruction

View handling instruction

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.

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

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.