431077-35-9
431077-35-9 structure
- Name: PPI-2458
- Chemical Name: [(3R,4S,5S,6R)-5-methoxy-4-[(2R,3R)-2-methyl-3-(3-methylbut-2-enyl)oxiran-2-yl]-1-oxaspiro[2.5]octan-6-yl] N-[(2R)-1-amino-3-methyl-1-oxobutan-2-yl]carbamate
- CAS Number: 431077-35-9
- Molecular Formula: C22H36N2O6
- Molecular Weight: 424.53100
- Catalog: Research Areas Cancer
- Create Date: 2016-04-03 20:35:00
- Modify Date: 2025-08-27 13:09:57
-
PPI-2458 is a potent, orally active, selective and irreversible inhibitor of methionine aminopeptidase-2 (MetAP-2). PPI-2458 can be used for arthritis and lymphoma research[1][2].
| Name | [(3R,4S,5S,6R)-5-methoxy-4-[(2R,3R)-2-methyl-3-(3-methylbut-2-enyl)oxiran-2-yl]-1-oxaspiro[2.5]octan-6-yl] N-[(2R)-1-amino-3-methyl-1-oxobutan-2-yl]carbamate |
|---|---|
| Synonyms |
Metapro
Carbamic acid,((1R)-1-(aminocarbonyl)-2-methylpropyl)-,(3R,4S,5S,6R)-5-methoxy-4-((2R,3R)-2-methyl-3-(3-methyl-2-butenyl)oxiranyl)-1-oxaspiro(2.5)oct-6-yl ester PPI-2458 [(3R,6R,7S,8S)-7-methoxy-8-[(2R,3R)-2-methyl-3-(3-methylbut-2-enyl)oxiran-2-yl]-2-oxaspiro[2.5]octan-6-yl] N-[(2R)-1-amino-3-methyl-1-oxobutan-2-yl]carbamate |
| Description | PPI-2458 is a potent, orally active, selective and irreversible inhibitor of methionine aminopeptidase-2 (MetAP-2). PPI-2458 can be used for arthritis and lymphoma research[1][2]. |
|---|---|
| Related Catalog | |
| In Vitro | PPI-2458 可有效抑制 HUVEC 增殖，GI50 为0.2 nM，在1 nM 时最大抑制率大于 95%[1]。 PPI-2458 (0-100 nM, 6天)抑制 SU-DHL-16 细胞的增殖和MetAP-2[2]。 Cell Proliferation Assay[2] 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. |
| In Vivo | PPI-2458 (0-50 mg/kg，口服，隔日一次)逆转 PG-PS (25 mg/kg, i.p) 诱导的关节炎模型中的关节肿胀和炎症[1]。 PPI-2458 (0-3 mg/kg，鼻胃插管，隔日一次)可导致实验初代食蟹猴生发中心生发中心淋巴细胞减少[2]。 PPI-2458 (0-100 mg/kg，口服，隔日一次)以剂量依赖的方式显著抑制肿瘤生长在SR肿瘤异种移植的严重联合免疫缺陷小鼠中[2]。 Animal Model: Female Lewis rats (101–121 g, PG-PS (25 mg/kg, i.p.)-induced arthritis model)[1] 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[2] 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)[2] 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. |
| References |
| Molecular Formula | C22H36N2O6 |
|---|---|
| Molecular Weight | 424.53100 |
| Exact Mass | 424.25700 |
| PSA | 120.19000 |
| LogP | 3.65300 |