4-Aza-1-azoniabicyclo[2.2.2]octane, 1-[4-[4-[(4R,5R)-3,3-dibutyl-7-(dimethylamino)-2,3,4,5-tetrahydro-4-hydroxy-1,1-dioxido-1-benzothiepin-5-yl]phenoxy]butyl]-, methanesulfonate (1:1)

Product Name4-Aza-1-azoniabicyclo[2.2.2]octane, 1-[4-[4-[(4R,5R)-3,3-dibutyl-7-(dimethylamino)-2,3,4,5-tetrahydro-4-hydroxy-1,1-dioxido-1-benzothiepin-5-yl]phenoxy]butyl]-, methanesulfonate (1:1)
CAS289037-67-8
MFC37H59N3O7S2
MW722.01
EINECS
MOL File289037-67-8.mol

Chemical Properties

form	Solid
color	White to off-white

Usage And Synthesis

Description

SC-435 is an ileal apical sodium co-dependent bile acid transporter (ASBT) which inhibits plasma cholesterol.

Uses

SC-435 is an orally effective apical sodium codependent bile acid transporter (ASBT) inhibitor. SC-435 effectively removes neurotoxic bile acids and ammonia from the blood by inhibiting intestinal ASBT, thereby alleviating liver and brain damage caused by liver failure. SC-435 can alter hepatic cholesterol metabolism and lower plasma low-density lipoprotein-cholesterol concentrations[1] [2] [3].

in vivo

SC-435 (10 μg/1 g; Oral administration; 5-16 weeks) reduces liver and brain damage due to liver failure in mouse models of chronic liver disease induced by Streptozotocin (HY-13753) and acute liver failure induced by Azoxymethane (HY-111375)^[2]. SC-435 (0.03-0.1 g/100 g; Oral administration; 12 weeks) alone or in combination with Simvastatin (HY-17502) reduces LDL cholesterol concentration by altering hepatic cholesterol homeostasis and intravascular lipoprotein processing in guinea pig models of endogenous hypercholesterolemia^[3].

Animal Model:	Streptozotocin (HY-13753) or Azoxymethane (HY-111375) treated male C57BL/6J mice (25-30 g)^[2]
Dosage:	10 μg/1 g, 16 weeks; 10 μg/1 g, 5 days
Administration:	Oral administration (p.o.)
Result:	Reduced bile acids and ammonia concentrations in the blood and brain. Alleviated liver and brain damages.

Animal Model:	Hartley guinea pigs (250-300 g) with endogenous hypercholesterolemia^[3]
Dosage:	0.1 g/100 g SC-435; 0.03 g/100 g SC-435 combined with 0.05 g/100 g Simvastatin (HY-17502)
Administration:	Oral administration (p.o.); 12 weeks
Result:	Compared to the control group, CETP activity was 34% and 56% lower with SC-435 and the combination of SC-435 and Simvastatin, respectively. Compared to the control group, Cholesterol 7α-hydroxylase and HMG-CoA reductase activities were increased 2-fold with SC-435 and the combination of SC-435 and Simvastatin, respectively. Compared to the control group, HMG-CoA reductase mRNA expression was increased 33% with SC-435.

References

[1] West KL, et, al. 1-[4-[4[(4R,5R)-3,3-Dibutyl-7-(dimethylamino)-2,3,4,5-tetrahydro-4-hydroxy-1,1-dioxido-1-benzothiepin-5-yl]phenoxy]butyl]-4-aza-1-azoniabicyclo[2.2.2]octane methanesulfonate (SC-435), an ileal apical sodium-codependent bile acid transporter inhibitor alters hepatic cholesterol metabolism and lowers plasma low-density lipoprotein-cholesterol concentrations in guinea pigs. J Pharmacol Exp Ther. 2002 Oct;303(1):293-9. DOI:10.1124/jpet.102.038711
[2] Xie G, et al. Dysregulated bile acid signaling contributes to the neurological impairment in murine models of acute and chronic liver failure. EBioMedicine. 2018 Nov;37:294-306. DOI:10.1016/j.ebiom.2018.10.030
[3] West KL, et al. SC-435, an ileal apical sodium-codependent bile acid transporter inhibitor alters mRNA levels and enzyme activities of selected genes involved in hepatic cholesterol and lipoprotein metabolism in guinea pigs. J Nutr Biochem. 2005 Dec;16(12):722-8. DOI:10.1016/j.jnutbio.2005.06.009

4-Aza-1-azoniabicyclo[2.2.2]octane, 1-[4-[4-[(4R,5R)-3,3-dibutyl-7-(dimethylamino)-2,3,4,5-tetrahydro-4-hydroxy-1,1-dioxido-1-benzothiepin-5-yl]phenoxy]butyl]-, methanesulfonate (1:1) Supplier

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