ASM-IN-1

• CAT Number: I041413
• CAS Number: 2913151-46-7
• Molecular Formula: C16H12BrN3O4
• Molecular Weight: 390.19
• Purity: ≥95%
• Synonyms: 3-[4-[(4-bromophenoxy)methyl]phenyl]-N-hydroxy-1,2,4-oxadiazole-5-carboxamide
• InChI: InChI=1S/C16H12BrN3O4/c17-12-5-7-13(8-6-12)23-9-10-1-3-11(4-2-10)14-18-16(24-20-14)15(21)19-22/h1-8,22H,9H2,(H,19,21)
• InChIKey: YYAPAXZETRKZHT-UHFFFAOYSA-N
• SMILES: C1=CC(=CC=C1COC2=CC=C(C=C2)Br)C3=NOC(=N3)C(=O)NO

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].
ASM-IN-1 (compound 4i) (0-20 µM) dose not affect cell growth in HUVECs[1].
ASM-IN-1 (0, 1, 5 µM) reduces the expressions of IL-6 and TNF-α with LPS stimulated in a dose-dependent manner, decreases the expression of MCP-1 mRNA in HUVECs[1].
ASM-IN-1 (5 µM) reduces Ox-LDL-stimulated MCP-1 mRNA expression and restore IL-6 mRNA to a normal level[1].
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]

Reference

[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.
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