Last update 01 Nov 2024

SOAT2

Last update 01 Nov 2024

Basic Info

Synonyms

ACACT2, ACAT-2, ACAT2

+ [4]

Introduction

Catalyzes the formation of fatty acid-cholesterol esters, which are less soluble in membranes than cholesterol (PubMed:16647063, PubMed:11294643). Plays a role in lipoprotein assembly and dietary cholesterol absorption (PubMed:11294643). Utilizes oleoyl-CoA ((9Z)-octadecenoyl-CoA) and linolenoyl-CoA ((9Z,12Z,15Z)-octadecatrienoyl-CoA) as substrates (PubMed:11294643). May provide cholesteryl esters for lipoprotein secretion from hepatocytes and intestinal mucosa (PubMed:11294643). Has lower enzymatic activity compared to isoform 1. Has lower enzymatic activity compared to isoform 1.

Drugs associated with SOAT2

PRD-003

Target

SOAT2

Mechanism

SOAT2 inhibitors

Active Org.

PRD Therapeutics, Inc.Startup

Originator Org.

PRD Therapeutics, Inc.Startup

Active Indication

Hyper LDL cholesterolaemia

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

helvamide

Target

SOAT1 x SOAT2

Mechanism

SOAT1 inhibitors [+1]

Active Org.

Kitasato University

Originator Org.

Kitasato University

Active Indication-

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

PRD-002

Target

PCSK9 x SOAT2

Mechanism

PCSK9 inhibitors [+1]

Active Org.

PRD Therapeutics, Inc.Startup

Originator Org.

PRD Therapeutics, Inc.Startup

Active Indication

Homozygous familial hypercholesterolemia [+1]

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with SOAT2

100 Translational Medicine associated with SOAT2

0 Patents (Medical) associated with SOAT2

Literatures (Medical) associated with SOAT2

01 Oct 2024·Advanced Science

siRNA/CS‐PLGA Nanoparticle System Targeting Knockdown Intestinal SOAT2 Reduced Intestinal Lipid Uptake and Alleviated Obesity

Article

Author: Xin, Hongliang ; Ni, Pu ; Shen, Weiyi ; Huang, Anhua ; Liang, Jingjia ; Zhang, Guixin ; Yang, Yulong ; Liu, Qian ; Gu, Aihua ; Shao, Wentao ; Jiang, Zhaoyan ; Wang, Qihan ; Kong, Weirui

AbstractEffective inhibition of intestinal lipid uptake is an efficient strategy for the treatment of disorders related to lipid metabolism. Sterol O‐acyltransferase 2 (SOAT2) is responsible for the esterification of free cholesterol and fatty acids into cholesteryl esters. We found that intestine‐specific SOAT2 knockout (Soat2I‐KO) mice was capable to prevent the development of dietary induced obesity due to reduced intestinal lipid absorption. Soat2 siRNA/CS‐PLGA nanoparticle system was constructed to enable intestinal delivery and inhibition of Soat2. This nanoparticle system was composed of PLGA‐block‐PEG and chitosan specifically delivering Soat2 siRNAs into small intestines in mice, effectively inhibit intestinal lipid uptake and resolving obesity. In revealing the underlying mechanism by which intestinal SOAT2 regulating fatty acid uptake, enhanced CD36 ubiquitination degradation was found in enterocytes upon SOAT2 inhibition. Insufficient free cholesterol esterification promoted endoplasmic reticulum stress and recruitment of E3 ligase RNF5 to activate CD36 ubiquitination in SOAT2 knockdown enterocytes. This work demonstrates a potential modulatory function of intestinal SOAT2 on lipid uptake highlighting the therapeutic effect on obesity by targeting intestinal SOAT2, exhibiting promising translational relevance in the siRNA therapeutic–based treatment for obesity.

01 Sep 2024·Phytomedicine

Investigating the potential mechanism and therapeutic effects of SLXG for cholesterol gallstone treatment

Article

Author: Zhou, Tong ; Wang, Wujie ; Li, Yuliang ; Liu, Bin ; Wang, Jiaxing ; Wang, Yang ; Chen, Zitong

BACKGROUNDShugan Lidan Xiaoshi Granules (SLXG) is a traditional Chinese medicine (TCM) formulation frequently employed to prevent and treat cholesterol gallstones. SLXG is formulated based on the Chaihu Shugan Formula found in an ancient Chinese medical book, a traditional remedy in China for centuries, and has demonstrated successful treatment of numerous patients with gallbladder stones.PURPOSEThis research sought to clarify the therapeutic impact and molecular mechanisms of SLXG and its active components in the treatment of cholesterol gallbladder stones.METHODSThe study employed network pharmacology, UPLC-HRMS transcriptome sequencing, animal model experiments, molecular docking, and Surface Plasmon Resonance (SPR) to explore the molecular mechanisms of SLXG and its relationship with Traditional Chinese Medicines (TCMs) and potential targets. Furthermore, PPI network analysis, along with GO and KEGG enrichment analyses, were performed to explore the potential mechanisms through which SLXG and its active ingredient, naringenin, prevent and treat cholesterol gallstones. The mechanism of action was further elucidated using an animal model for gallbladder stone formation.RESULTSThe study employed a network pharmacology and UPLC-HRMS to investigate the active compounds of SLXG for the treatment of cholesterol gallbladder stones, and subsequently constructed a network of therapeutic targets of SLXG. The results from gene enrichment analyses indicated that SLXG targets the metabolic pathway of bile secretion and the cholesterol metabolism pathway in addressing cholesterol gallbladder stones. The molecular docking results confirmed the interaction between the genes enriched in the pathways and the active ingredients in SLXG. Transcriptome sequencing results demonstrated that SLXG exerts its therapeutic effect on gallstones by regulating cholesterol and bile acid synthesis and metabolism. Furthermore, animal model experiments and SPR provided evidence that SLXG and its active ingredient, naringenin, exert therapeutic effects on cholesterol gallbladder stones by targeting the genes HMGCR, SOAT2, and UGT1A1, and influencing substances associated with cholesterol synthesis and metabolism.CONCLUSIONSUsing systematic network pharmacology methods combined with in vivo validation experiments, we uncovered the fundamental pharmacological effects and potential mechanisms of SLXG and its active ingredient, naringenin, in the treatment of cholesterol gallstones. This research underscores the valuable role that traditional remedies can play in addressing medical challenges and suggests a promising direction for further exploration of natural treatments for the disease.

01 Aug 2024·Naunyn-Schmiedeberg's Archives of Pharmacology

Soat2 inhibitor avasimibe alleviates acute pancreatitis by suppressing acinar cell ferroptosis

Article

Author: Sun, Hui ; Pan, Jiajia ; Zhang, Siqin ; Chen, Lin ; Xiao, Weiming ; Luo, Weiwei ; Dong, Xiaowu ; Wang, Yaodong ; Lu, Guotao ; Xu, Hongwei

Ferroptosis, characterized by lipid peroxidation, plays a significant role in the pathogenesis of acute pancreatitis (AP). While sterol O-acyltransferase 2 (Soat2) is known for its crucial regulatory role in cholesterol homeostasis, its involvement in the development of AP remains unreported. We conducted this study to identify the pivotal role of Soat2 in AP using transcriptomic databases. Subsequently, we confirmed its alterations through both in vitro and in vivo experimental models. Furthermore, we performed intervention with the Soat2 inhibitor avasimibe to evaluate pancreatic tissue pathology and serum enzymatic levels and observe inflammatory cell infiltration through immunohistochemistry. Additionally, changes in indicators related to ferroptosis were also observed. The results showed that in the AP mouse model, the protein and mRNA levels of Soat2 were significantly increased. Following avasimibe administration, there was a decrease in serum amylase levels, reduction in pancreatic tissue pathological damage, and attenuation of inflammatory cell infiltration. Furthermore, avasimibe administration resulted in downregulation of ferroptosis-related indicators. In conclusion, our findings suggest that the Soat2 inhibitor avasimibe protects against AP in mice through inhibition of the ferroptosis.

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