| Identification | Back Directory | [Name]
1,2,4-Oxadiazole-5-carboxamide, 3-[4-[(4-bromophenoxy)methyl]phenyl]-N-hydroxy- | [CAS]
2913151-46-7 | [Synonyms]
ASM-IN-1
1,2,4-Oxadiazole-5-carboxamide, 3-[4-[(4-bromophenoxy)methyl]phenyl]-N-hydroxy- | [Molecular Formula]
C16H12BrN3O4 | [MOL File]
2913151-46-7.mol | [Molecular Weight]
390.19 |
| Hazard Information | Back Directory | [Uses]
ASM-IN-1 is a potent and orally active acid sphingomyelinase (ASM) inhibitor with an IC50 value of 1.5 μM. ASM-IN-1 reduces lipid plaques in the aortic arch and aorta and reduces plasma ceramide concentration and Ox-LDL levels. ASM-IN-1 shows antiatherosclerotic and anti-inflammatory activity[1]. | [in vivo]
ASM-IN-1 (1 mg/kg for i.v.; 10 mg/kg for p.o.) shows good pharmacokinetic properties with good oral bioavailability of 35.42% in ICR mice[1].
ASM-IN-1 (6, 12, 40 mg/kg; i.p.; twice a day for 8 weeks) antiatherosclerotic activity by inhibiting ASM in mice[1].
Pharmacokinetic Parameters of ASM-IN-1 in ICR mice[1].
| parameter | iv | po | | T1/2 (h) | 0.20 ± 0.04 | 0.83 ± 0.32 | | Tmax (h) | 0.083 ± 0.00 | 0.083 ± 0.00 | | Cmax (ng/mL) | 787 ± 64.7 | 2763 ± 485 | | AUC0-t (h·ng/mL) | 227 ± 14.3 | 805 ± 76.7 | | AUC0-∞ (h·ng/mL) | 228 ± 15.1 | 809 ± 75.1 | | Vz (mL/kg) | 1277 ± 216 | | | CL (mL/h/kg) | 4390 ± 291 | | | MRT0-t (h) | 0.077 ± 0.012 | 0.32 ± 0.078 | | MRT0-∞ (h) | 0.087 ± 0.019 | 0.35 ± 0.064 | | F (%) | | 35.42 ± 0.033% |
ICR mice, 1 mg/kg iv ; 10 mg/kg po [1] | [References]
[1] Yang K, et al. Discovery of Novel N-Hydroxy-1,2,4-oxadiazole-5-formamides as ASM Direct Inhibitors for the Treatment of Atherosclerosis. J Med Chem. 2023 Feb 23;66(4):2681-2698. DOI:10.1021/acs.jmedchem.2c01643 |
|
|