BGT-002 has a dual mechanism of action. As an ACLY inhibitor, it blocks the production of acetyl-CoA, the key building block for fatty acid and cholesterol synthesis, thereby reducing lipogenesis. Simultaneously, as a PPARalpha agonist, it promotes the efflux and beta-oxidation of fatty acids, clearing lipids from the liver. This combined strategy of reducing production and increasing disposal leads to a potent lipid-lowering effect.

BGT-002 (3-50 μmol/L, 4 h) inhibits ACLY activity and lipid synthesis in mouse primary hepatocytes by acting as a prodrug for its active ACLY inhibitory CoA-thioester metabolite [2]. BGT-002 (12.5-50 μmol/L, 24 h) increases cholesterol efflux in mouse primary hepatocytes by upregulating ABCG5/8 transporter [2].

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In vitro, BGT-002 is a potent, dual-acting compound. It effectively inhibits the enzymatic activity of ATP-citrate lyase (ACLY). It also acts as an agonist for peroxisome proliferator-activated receptor alpha (PPARalpha), with an EC50 in the low micromolar range. In human HepG2 hepatoma cells, BGT-002 treatment is expected to reduce cellular lipid accumulation, as it blocks synthesis and promotes breakdown.

BGT-002 (15, 30, and 60 mg/kg, orally, once daily for 9 weeks) improves MASH in frozen animal models by dual opsonizing ACLY and PPARα [1]. BGT-002 (20 mg/kg, orally, once daily for 18 weeks) improves MASH and restores fibrosis in cynomolgus monkeys [1]. BGT-002 (10, 30, and 100 mg/kg, elbow, single dose) significantly inhibits de novo fat generation in the septum of diet-refeed eyebrows [2]. BGT-002 (30 mg/kg, elbow, single or once daily for 7 days) increases lumbar outflow induced by high-waisted diets and reduces lumbar hip [2]. BGT-002 (7.5, 15, 20 and 30 mg/kg, neck, once daily for 2 weeks) BGT-002 (15, 30 and 60 mg/kg, oral, once daily for 24 weeks) improved atherosclerotic thrombosis in a Western diet (WD)-induced ApoE-/- model [2].

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In vivo studies have demonstrated that BGT-002 effectively improves metabolic dysfunction-associated steatohepatitis (MASH) and alleviates hyperlipidemia in preclinical disease models. It is an orally active agent, and its dual mechanism has shown significant efficacy in reducing liver steatosis, inflammation, and fibrosis. BGT-002 is currently being studied for its potential in treating hypercholesterolemia and MASH.

ACLY activity is measured in an enzyme assay using purified human ACLY. The enzyme is incubated with its substrates (citrate, CoA, and ATP) in the presence of varying concentrations of BGT-002. The reaction product, CoA, is detected by its reaction with DTNB (Ellman's reagent), which produces a color change measurable at 412 nm. The IC50 value is the concentration that inhibits 50% of the enzyme activity. PPARalpha activation is measured using a cell-based luciferase reporter gene assay.

PPARalpha activation is assessed using a reporter gene assay in HEK293 cells. Cells are transiently transfected with a PPARalpha expression vector and a PPRE (PPAR response element)-luciferase reporter construct. After transfection, cells are treated with varying concentrations of BGT-002 (0.01-10 microM) for 24 h. Luciferase activity is measured. The EC50 is the concentration required to achieve 50% of the maximal PPARalpha-mediated transactivation.

Animal/Disease Models: Ob/ob mice fed with a high-fat, highfructose, high-cholesterol diet[1]
Doses: 15, 30, and 60 mg/kg
Route of Administration: p.o., daily for 9 weeks
Experimental Results: Did not significantly alter body weight or food intake. Significantly lowered MASH diet-induced elevations in ALT and AST levels and reduced plasma lipids. Notably reduced liver weight and NAS score. Significantly reduced CD68 and F4/80 levels in liver, and downregulated the expression of genes related to liver inflammation and fibrosis.

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Animal/Disease Models: Ob/ob mice fed with a choline-deficient L-amino aciddefined high-fat diet (CDAA-HFD)[1]
Doses: 15, 30, and 60 mg/kg
Route of Administration: p.o., daily for 9 weeks
Experimental Results: Significantly lowered plasma TG, ALT, and AST, without changing body weight or food intake. Alleviated CDAA-HFD induced hepatic steatosis and attenuated liver fibrosis. Significantly downregulated inflammatory and fibrotic gene expression. Alleviated CDAA-HFD-induced hepatic steatosis beyond ACLY. PPARα is required to ameliorate CDAA-HFD-induced MASH.

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Animal/Disease Models: MASH cynomolgus monkeys (≥8 years old)[1]
Doses: 20 mg/kg
Route of Administration: p.o., daily for 18 weeks
Experimental Results: Steadily lowered serum ALT, AST, and γ-GTT compared with the vehicle. Returned plasma total cholesterol (TC) and LDL-C to baseline over time. Reduced high-sensitivity C-reactive protein (hs-CRP), increased serum BHB and FAO levels. Resulted ACLY inhibition and PPARα activation with a safe profile.

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Animal/Disease Models: C57BL/6J mice fasted for 48 h followed by refeeding for another 48h[1]
Doses: 10, 30, and 100 mg/kg
Route of Administration: p.o., single dose
Experimental Results: Reduced lipogenesis specifically in the liver but not obviously in the muscle, heart, ileum, abdominal adipose or kidney tissues.

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Animal/Disease Models: Male golden hamsters fed with a high-fat and high-cholesterol (HFHC) die[2]
Doses: 7.5, 15 and 30 mg/kg
Route of Administration: p.o., daily for 2 weeks
Experimental Results: Exhibited a dose-dependent improvement in the hypolipidemic effect. Reduced serum TG and HDL-C levels.

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Animal/Disease Models: Male rhesus monkeys (6-20 years old) with mild or moderate hyperlipidemia for more than 2 years[2]
Doses: 20 mg/kg
Route of Administration: p.o., daily for 2 weeks
Experimental Results: Reduced plasma concentrations of TG, LDL-C and TC.

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Animal/Disease Models: ApoE-/- induced with Western diet (WD)[2]
Doses: 15, 30, and 60 mg/kg
Route of Administration: p.o., daily for 24 weeks
Experimental Results: Significantly decreased body weight gain. Significantly decreased cholesterol and LDL-C levels. Reduced expression of the inflammatory-related genes Cd68, F4/80 and IL-1β in a dose dependent manner.

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The efficacy of BGT-002 is evaluated in a mouse model of MASH, such as the choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) model. Male C57BL/6J mice are fed a CDAHFD for 4-8 weeks to induce steatohepatitis and fibrosis. Mice are then dosed daily with BGT-002 (e.g., 10, 30, 100 mg/kg) or a vehicle control via oral gavage for 4-6 weeks. Endpoints include liver histology (NAS score, fibrosis by Sirius Red), liver triglycerides and cholesterol, and serum ALT and cholesterol levels.

BGT-002 is an orally active compound. A Phase I clinical trial has been conducted to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of BGT-002 in healthy Chinese adults. The results from this trial would provide key PK parameters such as Cmax, Tmax, half-life (t½), and oral bioavailability. The compound is in early-stage clinical development.

BGT-002 has advanced into clinical development and has been evaluated in a Phase I clinical trial in healthy volunteers. This trial would have assessed its safety profile. Common adverse events associated with ACLY inhibitors (e.g., bempedoic acid) and PPARalpha agonists (e.g., fibrates) include gastrointestinal disturbances and potential muscle-related effects. Preclinical toxicology would have been conducted to support these clinical studies.

[1]. The enedioic acid analog 326E alleviates metabolic dysfunction-associated steatohepatitis via dual targeting at ACLY and PPARα. Cell Metab. 2025 Nov 4;37(11):2149-2166.e9.

[2]. Development of the novel ACLY inhibitor 326E as a promising treatment for hypercholesterolemia. Acta Pharm Sin B. 2023 Feb;13(2):739-753.

[3]. Simultaneous determination of BGT-002 and its acyl glucuronide metabolite ZM326E-M2 in human plasma by liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study. J Pharm Biomed Anal. 2024 Jun 15;243:116056.

BGT-002 (CAS# 2127387-94-2) is a research-stage, dual-acting small molecule with a novel mechanism of action. It is an ATP-citrate lyase (ACLY) inhibitor and a PPARalpha agonist being developed as a potential treatment for metabolic diseases like MASH and hypercholesterolemia. As of now, BGT-002 is not an FDA-approved drug; it is in Phase I clinical trials.

C19H34O4

326.47

326.246

2127387-94-2

140959769

Typically exists as solids at room temperature

2

13

23

394

0

CC(C)(CCCCC/C=C/CCCCC(C)(C)C(=O)O)C(=O)O

UUPWWWGROSGLPP-AATRIKPKSA-N

InChI=1S/C19H34O4/c1-18(2,16(20)21)14-12-10-8-6-5-7-9-11-13-15-19(3,4)17(22)23/h5-6H,7-15H2,1-4H3,(H,20,21)(H,22,23)/b6-5+

(E)-2,2,14,14-tetramethylpentadec-7-enedioic acid

326E

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)