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Last update 08 May 2025

MOGAT2

Last update 08 May 2025

Basic Info

Synonyms

2-acylglycerol O-acyltransferase 2, Acyl-CoA:monoacylglycerol acyltransferase 2, DC5

+ [9]

Introduction

Involved in glycerolipid synthesis and lipid metabolism (PubMed:12621063, PubMed:18768481, PubMed:27184406, PubMed:28420705). Catalyzes the formation of diacylglycerol, the precursor of triacylglycerol, by transferring the acyl chain of a fatty acyl-CoA to a monoacylglycerol (PubMed:12621063, PubMed:27184406). Plays a central role in absorption of dietary fat in the small intestine by catalyzing the resynthesis of triacylglycerol in enterocytes (By similarity). Has a preference toward monoacylglycerols containing unsaturated fatty acids in an order of C18:3 > C18:2 > C18:1 > C18:0 at sn-2 (PubMed:12621063). Able to use 1-monoalkylglycerol (1-MAkG, 1-O-alkylglycerol) as an acyl acceptor for the synthesis of monoalkyl-monoacylglycerol (MAMAG, 1-O-alkyl-3-acylglycerol or 1-O-alkyl-2-acylglycerol) and subsequently, with lower efficiency, may add another acyl chain producing monoalkyl-diacylglycerol (MADAG, 1-O-alkyl-2,3-diacylglycerol) (PubMed:28420705). Possesses weak but significant activity with diacylglycerol as substrate, producing triacylglycerol (triacyl-sn-glycerol) (PubMed:18768481).

Drugs associated with MOGAT2

S-309309

Target

MGAT2 x MOGAT2

Mechanism

MGAT2 inhibitors [+1]

Active Org.

Shionogi, Inc.

Originator Org.

Shionogi & Co., Ltd.

Active Indication

Obesity

Inactive Indication-

Drug Highest PhasePhase 2

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

MGAT2 inhibitors (VENENUM Biodesign)

Target

MOGAT2

Mechanism

MOGAT2 inhibitors

Active Org.

Venenum Biodesign LLC

Originator Org.

Venenum Biodesign LLC

Active Indication

Nonalcoholic Steatohepatitis

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with MOGAT2

NCT06106334

/ CompletedPhase 1

A Crossover, Phase 1, Open-label, One-arm Study to Investigate the Effect of Itraconazole on the Pharmacokinetics of S-309309 in Healthy Male and Female Participants

The primary purpose of this study is to determine the effect of repeated administration of itraconazole on the pharmacokinetic (PK) profile of S-309309; and the PK of S-309309 following administration of S-309309 alone and co-administration with itraconazole

Start Date15 Nov 2023

Sponsor / Collaborator

Shionogi & Co., Ltd.

NCT05925114

/ CompletedPhase 2

A Phase 2, Multicenter, Randomized, Double-blind, Dose-ranging, Placebo-controlled Study to Assess the Safety and Efficacy of S-309309 in Obese Adults

The primary objective of this study is to understand the efficacy of S-309309 on the body weight of obese adults.

Start Date21 Jun 2023

Sponsor / Collaborator

Shionogi, Inc.

NCT05247970

/ CompletedPhase 1

A Phase 1 Randomized, Double-blind, Single and Multiple-dose Study to Assess the Safety, Tolerability, Pharmacokinetics, Food Effect, and Drug-Drug Interactions of S-309309 in Healthy and Obese Adult Study Participants

The primary aim of the study is to assess the safety and tolerability of S-309309 after oral administration in healthy adult or obese but otherwise healthy adult participants. The secondary aim of the study is to assess the pharmacokinetics of S-309309 and the effects on ECG parameters after oral administration in healthy or obese but otherwise healthy participants.

Start Date04 Jan 2022

Sponsor / Collaborator

Shionogi, Inc.

100 Clinical Results associated with MOGAT2

100 Translational Medicine associated with MOGAT2

0 Patents (Medical) associated with MOGAT2

109

Literatures (Medical) associated with MOGAT2

01 May 2025·animal

Unravelling novel and closely linked association signals for fat-related traits in pigs using prioritised variants from whole-genome sequence data

Article

Author: Molinero, E ; Pena, R N ; Estany, J ; Ros-Freixedes, R

For most production traits, the largest proportions of genetic variance remain unmapped. Dense whole-genome sequence (WGS) data enable the possibility of discovering novel associations as well as unravelling closely linked association signals with a resolution that marker arrays cannot reach. However, the identification of variants from WGS data that are causal of the variation of complex traits is hindered by the high dimensionality and linkage disequilibrium. Thus, at best, we can narrow the circle around the causal variants to prioritise a set of variants for their posterior validation. In this study, we assessed the utility of WGS data for uncovering associations of weaker effects using, as a model, fat content and composition traits in a Duroc pig population where we previously described major effects of the LEPR and SCD genes. We genotyped 971 pigs for a set of 182 variants from 154 candidate genes that were prioritised from amongst the WGS variants discovered in 205 sequenced individuals. These variants were prioritised conditional to LEPR and SCD. The association of the prioritised variants with the target traits was then tested in the confirmation set of 971 pigs. A total of 17 potentially independent quantitative trait loci (8.4% of the total number of studied genes) were significantly associated (q-value < 0.05) with at least one of the studied traits. We identified novel associations attributable to genes such as ABCC2, MOGAT2, or PLPP1 for backfat thickness, myristic acid content, and monounsaturated fatty acid content, respectively. Our results also revealed a finer granularity of weaker genetic effects in loci such as those around the DGAT2 and FADS2 genes, which may mask the effects of closely located genes like MOGAT2 and DAGLA, respectively. To refine the prioritisation of variants for validation studies, especially when targeting those of weaker effects, we recommend larger and more diverse discovery sets, more precise and complete functional gene annotation, and the integration of other omics data.

01 Feb 2025·Clinical Drug Investigation

Safety, Tolerability, and Pharmacokinetics of a Novel Anti-obesity Agent, S-309309, in Healthy Adults with or Without Obesity

Article

Author: Kezbor, Safwan ; Sonoyama, Takuhiro ; Ishibashi, Toru ; Tanioka, Hideki ; Ikehara, Tatsuya

BACKGROUNDAnti-obesity medications are recommended for patients who do not achieve and maintain weight loss despite lifestyle interventions. S-309309 is a novel oral inhibitor of monoacylglycerol O-acyltransferase 2 being developed as a treatment for obesity.OBJECTIVEThe objective of the study was to investigate the safety, clinical pharmacology, pharmacokinetics and pharmacodynamic biomarker of S-309309.METHODSA phase I, single-center, two-part, randomized, double-blind, placebo-controlled study of S-309309 following oral administration of a single-ascending dose (part 1) and a multiple dose (part 2) in healthy adults with or without obesity was conducted. We also assessed the effect of food on the pharmacokinetics of S-309309 and the effect of S-309309 on electrocardiogram parameters, the pharmacokinetics of midazolam (a cytochrome P450 3A substrate), and the pharmacodynamic biomarker of monoacylglycerol O-acyltransferase 2 inhibition.RESULTSIn part 1 (N = 50), a single-ascending dose of S-309309 in healthy adults demonstrated dose proportionality and comparable exposure of S-309309 between the fasted and fed states. In part 2 (N = 24), no clinically meaningful difference was observed in the pharmacokinetics of multiple doses between healthy adults with or without obesity. S-309309 did not affect the pharmacokinetics of the cytochrome P450 3A substrate. The pharmacodynamic biomarker of monoacylglycerol O-acyltransferase 2 inhibition, dicarboxylic acid (18:1), was significantly increased after S-309309 administration in healthy adults with or without obesity. Overall, S-309309 demonstrated acceptable safety and tolerability without any serious adverse events or discontinuations because of adverse events, and did not have a clinically relevant effect on the heart rate or cardiac conduction. An effect on the placebo-corrected change-from-baseline corrected QT interval, corrected for heart rate using the Fridericia method, exceeding 10 ms can be excluded.CONCLUSIONSS-309309 was well tolerated as single-dose (up to 300 mg) and multiple-dose (50 mg once daily for 14 days) oral administration. The pharmacokinetic characteristics remained unaffected by obesity and food intake. S-309309 did not affect the pharmacokinetics of the cytochrome P450 3A substrate. Overall, S-309309 had an acceptable safety profile and favorable pharmacokinetic and pharmacodynamic characteristics.CLINICAL TRIAL REGISTRATIONNCT05247970, date of registration: 8 February, 2022.

01 Jul 2024·Heliyon

Development and validation of prognostic signatures of NAD+ metabolism and immune-related genes in colorectal cancer

Article

Author: Huang, Hong ; Yu, Yuanao ; Ye, Tao ; Jiang, Li ; Yue, Dongqin ; Wu, Huixian ; Chen, Kangli ; Zhang, Ning

BackgroundColorectal cancer (CRC) is a prevalent cause of death from malignant tumors. This study aimed to develop a nicotinamide adenine dinucleotide (NAD+) metabolism and immune-related prognostic signature, providing a theoretical foundation for prognosis and therapy in CRC patients.MethodsNAD + metabolism-related and immune-related subtypes of CRC patients were identified by consistent clustering. Differentially expressed genes (DEGs) between the two subtypes of CRC were identified by overlapping. A risk signature was constructed using univariate Cox and least absolute shrinkage and selection operator (LASSO) regression analyses. Independent prognostic predictors were authenticated by Cox analysis. Gene set variation analysis (GSVA) and single-sample gene set enrichment analysis (ssGSEA) were applied to investigate the connection between the prognostic signature and the immune microenvironment. Chemotherapy drug sensitivity and immunotherapy responsiveness were projected using the 'pRRophetic' package and Tumor Immune Dysfunction and Exclusion (TIDE) website. The Human Protein Atlas (HPA) database was used to assess the protein expression of prognostic genes in CRC and normal tissues.ResultsUsing bioinformatics methods, three prognostic genes related to immune-related NAD + metabolism were identified, and the results were used to establish and verify a prognostic signature related to immune-related NAD + metabolism in CRC patients. Cox regression analysis confirmed that the risk score was a reliable independent prognostic predictor. GSVA and ssGSEA indicated that the prognostic signature was associated with the immune microenvironment. TIDE analysis suggested that the signature might act as an immunotherapy predictor. Chemotherapy sensitivity analysis revealed that COMP was correlated with chemotherapy sensitivity in CRC patients and might be a potential therapeutic target.ConclusionThis study identified NAD + metabolism-immune-related prognostic genes (MOGAT2, COMP, and DNASE1L3) and developed a prognostic signature for CRC prognosis, which is significant for clinical prognosis prediction and treatment strategy decisions for CRC patients.

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