SC-435, an ileal apical sodium co-dependent bile acid transporter (ASBT) inhibitor lowers plasma cholesterol and reduces atherosclerosis in guinea pigs

West, Kristy L.; Zern, Tosca L.; Butteiger, Dustie N; Keller, Bradley T.; Fernández, María Luz

doi:10.1016/j.atherosclerosis.2003.08.019

Cited by 62 publications

(62 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several in vivo studies were performed with SC-435 treatment in Hartley guinea pigs, miniature pigs, New Zealand White rabbits and dogs. Concordantly, these studies found an increase of faecal bile acid excretion, decreased total and LDL-cholesterol plasma levels, and enhanced expression of the hepatic LDL receptor, secondary to the upregulation of hepatic cholesterol 7α-hydroxylase (CYP7A1) expression (Huff et al 2002;West et al 2002West et al , 2003Bhat et al 2003;Telford et al 2003;Li et al 2004).…”

Section: Pharmacological Inhibition Of the Asbtmentioning

confidence: 70%

The solute carrier family SLC10: more than a family of bile acid transporters regarding function and phylogenetic relationships

Geyer

Wilke

Petzinger

2006

Naunyn Schmied Arch Pharmacol

161

138

View full text Add to dashboard Cite

The solute carrier family 10 (SLC10) comprises two sodium-dependent bile acid transporters, i.e. the Na + / taurocholate cotransporting polypeptide (NTCP; SLC10A1) and the apical sodium-dependent bile acid transporter (ASBT; SLC10A2). These carriers are essentially involved in the maintenance of the enterohepatic circulation of bile acids mediating the first step of active bile acid transport through the membrane barriers in the liver (NTCP) and intestine (ASBT). Recently, four new members of the SLC10 family were described and referred to as P3 (SLC10A3), P4 (SLC10A4), P5 (SLC10A5) and sodium-dependent organic anion transporter (SOAT; SLC10A6). Experimental data supporting carrier function of P3, P4, and P5 is currently not available. However, as demonstrated for SOAT, not all members of the SLC10 family are bile acid transporters. SOAT specifically transports steroid sulfates such as oestrone-3-sulfate and dehydroepiandrosterone sulfate in a sodium-dependent manner, and is considered to play an important role for the cellular delivery of these prohormones in testes, placenta, adrenal gland and probably other peripheral tissues. ASBT and SOAT are the most homologous members of the SLC10 family, with high sequence similarity (∼70%) and almost identical gene structures. Phylogenetic analyses of the SLC10 family revealed that ASBT and SOAT genes emerged from a common ancestor gene. Structure-activity relationships of NTCP, ASBT and SOAT are discussed at the amino acid sequence level.Based on the high structural homology between ASBT and SOAT, pharmacological inhibitors of the ASBT, which are currently being tested in clinical trials for cholesterollowering therapy, should be evaluated for their crossreactivity with SOAT.

show abstract

Section: Pharmacological Inhibition Of the Asbtmentioning

confidence: 70%

The solute carrier family SLC10: more than a family of bile acid transporters regarding function and phylogenetic relationships

Geyer

Wilke

Petzinger

2006

Naunyn Schmied Arch Pharmacol

161

138

View full text Add to dashboard Cite

show abstract

“…So far, a number of ASBT inhibitors having various structural characteristics have been synthesized. Among of them, three candidates-264W94, SC-435 and R-146224 ( Figure 1) were reported to block bile acid re-absorption and reduce cholesterol levels significantly in animal models [14][15][16]. In addition, it has recently been demonstrated in a Phase Ⅲ trial that A3309 (Figure 1), another ASBT inhibitor, can be used to treat patients with chronic idiopathic constipation (CIC).…”

Section: Introductionmentioning

confidence: 99%

Arylsulfonylamino-Benzanilides as Inhibitors of the Apical Sodium-Dependent Bile Salt Transporter (SLC10A2)

Liu

Xiu-juan

et al. 2013

Molecules

View full text Add to dashboard Cite

Abstract:The apical sodium-dependent bile salt transporter (ASBT) plays a pivotal role in maintaining bile acid homeostasis. Inhibition of ASBT would reduce bile acid pool size and lower cholesterol levels. In this report, a series of novel arylsulfonylaminobenzanilides were designed and synthesized as potential inhibitors of ASBT. Most of them demonstrated great potency against ASBT's bile acid transport activity. In particular, compound 5g 2 inhibited ASBT activity with an IC 50 value of 0.11 μM. These compounds represent potential cholesterol-lowering drugs.

show abstract

“…The amount of cholesterol was either low (0.04 g/100 g) or high (0.25 g/100 g), equivalent to 300 mg/d or 1,800 mg/d in the human situation, respectively 13) . The high cholesterol was given to develop atherosclerosis in guinea pigs 12) .…”

Section: Dietsmentioning

confidence: 99%

“…The extraction solution was mixed with acidified water to separate into two phases, which were then filtered by gravity filtration. The lower phase was separated and an aliquot of 200 L was evaporated completely and reconstituted with 200 L ethanol for enzymatic determination of free cholesterol 12) .…”

Section: Aortic Lipidsmentioning

confidence: 99%

“…Therefore, it is possible that CR can reduce the lipid accumulation in arterial wall and prevent deleterious effects in the aorta's mechanical properties. Our lab group has shown that guinea pigs are an adequate model for the study of atherosclerosis and inflammation [10][11][12] . The aim of this study was to evaluate the effect of CR on the factors that contribute to the development atherosclerosis, such as inflammation, lipid accumulation in aorta, sPLA2 activity, and arterial mechanical properties (stiffness and energy absorption capability) in guinea pigs.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Carbohydrate Restriction Reduces Lipids and Inflammation and Prevents Atherosclerosis in Guinea Pigs

Torres-Gonzalez

Volek

Leite

et al. 2008

JAT

View full text Add to dashboard Cite

SC-435, an ileal apical sodium co-dependent bile acid transporter (ASBT) inhibitor lowers plasma cholesterol and reduces atherosclerosis in guinea pigs

Cited by 62 publications

References 37 publications

The solute carrier family SLC10: more than a family of bile acid transporters regarding function and phylogenetic relationships

The solute carrier family SLC10: more than a family of bile acid transporters regarding function and phylogenetic relationships

Arylsulfonylamino-Benzanilides as Inhibitors of the Apical Sodium-Dependent Bile Salt Transporter (SLC10A2)

Carbohydrate Restriction Reduces Lipids and Inflammation and Prevents Atherosclerosis in Guinea Pigs

Contact Info

Product

Resources

About