PPI-2458

Research use only, not for human use.

PPI-2458 is potent, specific, irreversible methionine aminopeptidase-2 (MetAP-2) inhibitor with IC50 of 0.2 nM.

PPI-2458 is potent, specific, irreversible methionine aminopeptidase-2 (MetAP-2) inhibitor with IC50 of 0.2 nM, inhibits growth inhibition of HFLS-RA and HUVEC with IC50 of 0.04 nM; significantly attenuates paw swelling when therapeutically administered after the onset of chronic disease in rat model of peptidoglycan-polysaccharide-induced arthritis; exhibits potent antiproliferative activity on NHL lines in vitro (GI50=0.2-1.9 nM) and oral antitumor activity in vivo. Blood Cancer Discontinued.

Cell Proliferation Assay Cell Line:SU-DHL-16 cells Concentration:0, 0.01, 0.1, 1, 10, and 100 nM Incubation Time:6 days Result:Inhibited SU-DHL-16 proliferation in a dose-dependent fashion with maximum inhibition of 60% achieved at the highest concentration (100 nmol/L) and GI50 at 1.9 nmol/L.

Animal Model:Female Lewis rats (101–121 g, PG-PS (25 mg/kg, i.p.)-induced arthritis model)Dosage:0.25, 1, 5, and 50 mg/kg Administration:Orally (po), started at day 15 after the chronic destructive phase of the disease was established and terminated on day 31 Result:Significantly and dose-dependently attenuated the chronic inflammatory response. Markedly attenuated paw swelling in a dose-dependent manner with maximal protection at an orally administered dose of 50 mg/kg at day 31.Animal Model:Forty-two experimentally naive cynomolgus monkeys Dosage:0.1 mg/kg (three males and three females), 0.3 mg/kg (three males and three females), 1.0 mg/kg (five males and five females), and 3.0 mg/kg (five males and five females)Administration:Nasogastric intubation every other day (QOD) for 13 days (total of seven treatments) Result:Exhibited a marked decrease in germinal center lymphocytes.Animal Model:60 female Fox Chase severe combined immunodeficient mice (SR lymphoma cells were injected s.c. above the right hind leg) Dosage:10, 30, or 100 mg/kg Administration:oral gavage, QOD Result:Significantly suppressed tumor growth in a dose-dependent manner. PPI-2458 administered at 100 mg/kg produced the greatest degree of tumor growth inhibition, which was 57% (P < 0.001) at the end of the study.

PPI2458

Metabolic Enzyme/Protease

Aminopeptidase

Aminopeptidase

Cancer

Blood cancer

431077-35-9

424.53

C22H36N2O6

>98% (HPLC)

——

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

(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

(-20℃)

With Ice Pack

≥ 2 years