Seladelpar (MBX8025, RWJ800025)

Alias: MBX-8025; RWJ800025; MBX 8025; RWJ 800025; MBX8025; RWJ-800025

Cat No.:V14589 Purity: ≥98%

COA Product Data Instructions for use SDS

Seladelpar (formerly MBX-8025 and RWJ-800025) is a novel,orally bioactive and selective peroxisome proliferator-activated receptor (PPAR)-δ receptor agonist with anti-cholestatic effects.

Seladelpar (MBX8025, RWJ800025) Chemical Structure CAS No.: 851528-79-5
Product category: PPAR

This product is for research use only, not for human use. We do not sell to patients.

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Citations by Top Journals: Nature, Cell, Science, etc.

Top Publications Citing lnvivochem Products

Nature 2021, 597(7874):119-125.

Cell 2020,183:1202-1218.e25.

Science Adv 2022: 8, eabm9427.

Nature 597, 119–125 (2021)

Cell Stem Cell 2020,26(6):845-861.e12.

Science Trans Med 2023,15(701):eadd7872.

STTT 2023,8(1):91.

Cell Reports 2023,42(4):112313

Science Trans Med 2023, 15: eadd7872.

Cancer Cell 2021,39(4):529-547.e7.

Cancer Discov 2022,12(4):1106-1127.

Immunity 2023,56(3):620-634.e11.

J Am Chem Soc 2022,144:21831-21836.

Cell 2020,183:1202-1218.e25.

Science Adv 2022:8,eabm9427.

Nature 2021,597(7874):119-125.

Cell 2020,183:1202-1218.e25.

PNAS Nexus 2022,1(3):pgac063.

ACS Nano 2023,17(10):9110-9125.

Biomaterial 2023 Sep16:302:122333.

Purity & Quality Control Documentation

Current batch：

Purity: ≥98%

COA

MSDS

Instructions

Product Description
Bioactivity & Protocols
Physicochemical Properties
Solubility Data
Calculators
Clinical Trial Information
Biological Data

Product Description

Seladelpar (formerly MBX-8025 and RWJ-800025) is a novel, orally bioactive and selective peroxisome proliferator-activated receptor (PPAR)-δ receptor agonist with anti-cholestatic effects. Its EC50 of 2 nM indicates that it inhibits PPAR-δ. Seladelpar acts as an anti-inflammatory and anti-fibrotic agent through PPAR-delta agonism. Additionally, this method raises lipid metabolism and lowers bile acids. Phase 3 clinical trials are currently being conducted on selegelapar. Treatment for dyslipidemia, metabolic syndrome, type 2 diabetes, and non-alcoholic steatohepatitis may involve the use of selazelpar.

Biological Activity I Assay Protocols (From Reference)

Targets

PPAR-δ (EC50 = 2 μM); PPAR-α (EC50 = 1600 μM)

ln Vitro

Seladelpar (MBX-8025) is a PPAR-δ agonist that is being developed as a lipid-altering agent. It is orally active, potent (2 nM), and specific (>750-fold and >2500-fold compared with PPAR-α or PPAR-γ receptors, respectively)[1]. With a 50% effect concentration of human PPAR-δ = 2 nM and PPAR-α = 1,600 nM, seladelpar is a potent and selective PPAR-δ agonist that shows positive effects on atherogenic dyslipidemia, insulin resistance, and diabetes[2].

ln Vivo

Following weaning, wild-type littermates and female Alms1 mutant (foz/foz) mice are given an atherogenic diet for 16 weeks.After that, groups (n=8–12) are randomized to receive either vehicle (1% methylcellulose) or Seladelpar (10 mg/kg) by gavage for an additional 8 weeks. Seladelpar normalizes glucose disposal, hyperglycemia, and hyperinsulinemia in foz/foz mice while hardly changing body weight. In mice treated with a vehicle, the serum level of alanine aminotransferase ranges from 300 to 600 U/L; Seladelpar reduces this level by 50%. Furthermore, Seladelpar restores normalcy to serum lipid levels, hepatic levels of free cholesterol, and other lipotoxic lipids that exhibit elevation in vehicle-treated foz/foz mice relative to wild-type mice. This significantly reduced steatosis and liver inflammation, eliminated hepatocyte ballooning and apoptosis, and improved liver fibrosis. The mean nonalcoholic fatty liver disease activity score in vehicle-treated foz/foz mice is 6.9, indicating nonalcoholic steatohepatitis (NASH); in all foz/foz mice, selegilegpar reverses NASH (nonalcoholic fatty liver disease activity score 3.13). When administered to Wt mice fed an atherogenic diet, Seladelpar reduces body weight by approximately 18% (P<0.05). On the other hand, Seladelpar has little effect on body weight in mice fed an atherogenic diet (foz/foz). After sixteen weeks (P<0.05), these animals develop severe hyperglycemia, hyperinsulinemia, and whole-body insulin resistance; selegilapar remarkably improves these indices (P<0.05). Following intraperitoneal injection of glucose, blood glucose levels in vehicle-treated mice reach approximately 32 mM, while in Seladelpar-treated foz/foz mice they reach approximately 14 mM (P<0.05); Seladelpar-treated foz/foz mice also have a lower area under the blood glucose disappearance curve (P<0.05). Seladelpar has a comparable effect (P<0.05) on glucose handling in Wt mice fed an atherogenic diet[2].

Animal Protocol

Mice: Atherogenic diet (23 percent fat, 0.2 percent cholesterol, and 45 percent simple carbohydrate; 4.78 kcal/g digestible energy) is fed ad libitum to Alms1 mutant (foz/foz) NOD.B10 mice or Wt littermates (female mice in both groups) from the time of weaning (week 4). Following this, groups are randomized (n=8–12 mice/group) to once-daily oral administration (by gavage) of Seladelpar (10 mg/kg in 1% methylcellulose) or vehicle (controls) for 8 weeks. Animals are kept in housing with a 12-hour light/dark cycle, a constant temperature of 22°C, and the highest level of humane treatment[2].

References

[1]. MBX-8025, a novel peroxisome proliferator receptor-delta agonist: lipid and other metabolic effects in dyslipidemic overweight patients treated with and without atorvastatin. J Clin Endocrinol Metab. 2011 Sep;96(9):2889-97.

[2]. The selective peroxisome proliferator-activated receptor-delta agonist seladelpar reverses nonalcoholic steatohepatitis pathology by abrogating lipotoxicity in diabetic obese mice. Hepatol Commun. 2017 Jul 31;1(7):663-674.

These protocols are for reference only. InvivoChem does not independently validate these methods.

Physicochemical Properties

Molecular Formula	C21H23F3O5S
Molecular Weight	444.464535951614
Exact Mass	444.12
Elemental Analysis	C, 56.75; H, 5.22; F, 12.82; O, 18.00; S, 7.21
CAS #	851528-79-5
Related CAS #	Seladelpar sodium salt
Appearance	Solid powder
SMILES	CCO[C@H](COC1=CC=C(C=C1)C(F)(F)F)CSC2=CC(=C(C=C2)OCC(=O)O)C
InChi Key	JWHYSEDOYMYMNM-QGZVFWFLSA-N
InChi Code	InChI=1S/C21H23F3O5S/c1-3-27-17(11-28-16-6-4-15(5-7-16)21(22,23)24)13-30-18-8-9-19(14(2)10-18)29-12-20(25)26/h4-10,17H,3,11-13H2,1-2H3,(H,25,26)/t17-/m1/s1
Chemical Name	2-[4-[(2R)-2-ethoxy-3-[4-(trifluoromethyl)phenoxy]propyl]sulfanyl-2-methylphenoxy]acetic acid
Synonyms	MBX-8025; RWJ800025; MBX 8025; RWJ 800025; MBX8025; RWJ-800025
HS Tariff Code	2934.99.9001
Storage	Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility Data

Solubility (In Vitro)	DMSO: ~100 mg/mL (~225 mM)
Solubility (In Vivo)	Solubility in Formulation 1: ≥ 2.5 mg/mL (5.62 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.62 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.)

Solubility (In Vitro)

DMSO: ~100 mg/mL (~225 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.62 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

Solubility in Formulation 2: ≥ 2.5 mg/mL (5.62 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.2499 mL	11.2496 mL	22.4992 mL
	5 mM	0.4500 mL	2.2499 mL	4.4998 mL
	10 mM	0.2250 mL	1.1250 mL	2.2499 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

Calculator

Mass

Concentration

Volume

Molecular Weight*

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Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

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See Example

An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?

Enter 350.26 in the Molecular Weight (MW) box
Enter 10 in the Concentration box and choose the correct unit (mM)
Enter 5 in the Volume box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

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Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:

Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
Enter 25 into the Concentration (End) box and select the correct unit (mM)
Enter 25 into the Volume (End) box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box

Molecular formula

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g/mol

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Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4 c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

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Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
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The answer appears in the Volume (to add to vial) box

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)

Dosage mg/kg

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Dosing volume per animal μL

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Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)

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Calculation results

Working concentration： mg/mL；

Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O，mix and clarify.

Note： (1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.

Clinical Trial Information

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT04950764	Recruiting	Drug: Seladelpar 10 mg or less Drug: Seladelpar 10 mg	Compensated Cirrhosis Hepatic Impairment	CymaBay Therapeutics, Inc.	September 17, 2021	Phase 1
NCT06051617	Recruiting	Drug: Seladelpar 10 mg Drug: Placebo	Primary Biliary Cholangitis	CymaBay Therapeutics, Inc.	September 7, 2023	Phase 3
NCT06060665	Recruiting	Drug: Seladelpar 10 mg Drug: Placebo	Primary Biliary Cholangitis	CymaBay Therapeutics, Inc.	September 5, 2023	Phase 3
NCT03301506	Recruiting	Drug: Seladelpar 5 mg Capsule Drug: Seladelpar 10 mg Capsule	Primary Biliary Cirrhosis	CymaBay Therapeutics, Inc.	December 12, 2017	Phase 3
NCT03602560	Completed	Drug: seladelpar 5-10 mg Drug: seladelpar 10 mg	Primary Biliary Cholangitis	CymaBay Therapeutics, Inc.	October 1, 2018	Phase 3

Biological Data

Effects of MBX-8025 on LDL-C by baseline lipid level (tertile) compared with placebo, with or without ATV 20 mg/d. J Clin Endocrinol Metab . 2011 Sep;96(9):2889-97.
Effects of MBX-8025 on TG levels by baseline TG (tertile) compared with placebo, with or without ATV 20 mg/d. J Clin Endocrinol Metab . 2011 Sep;96(9):2889-97.

Effects of MBX-8025 with or without ATV 20 mg on the percentage of subjects with metabolic syndrome compared with placebo and ATV alone. *, P < 0.05 vs. placebo and vs. ATV; **, P < 0.01 vs. placebo and vs. ATV. P values for pairwise treatment comparisons were estimated from logistic regression. J Clin Endocrinol Metab . 2011 Sep;96(9):2889-97.

Effects of MBX‐8025 on body weight, hyperglycemia, hyperinsulinemia, serum ALT, cholesterol, and triglyceride in atherogenic diet–fed foz/foz and Wt mice. Hepatol Commun . 2017 Jul 31;1(7):663-674.

Effects of MBX‐8025 on hepatocyte apoptosis, proliferation, fibrosis, and liver inflammation in atherogenic diet–fed foz/foz and Wt mice. Hepatol Commun . 2017 Jul 31;1(7):663-674.