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Purity: ≥98%
Arhalofenate (formerly known as JNJ-39659100 and/or MBX102) is a novel, selective, partial agonist of PPAR-γ (peroxisome proliferator-activated receptor). It can reduce glucose levels without causing some of the negative effects of TZDs, like edema and weight gain. Arhalofenate is being developed clinically as an oral glucose-lowering medication to treat type 2 diabetes. Both in humans and preclinical rodent models, arhalofenate exhibits a significant reduction in triglyceride levels. Research conducted in vivo on ZDF and ZF rats showed that MBX-102 reduced plasma triglycerides. On the other hand, neither liver weight nor the amounts of PPAR-α target gene expression in the liver were affected by MBX-102 in ZF rats. Additional in vitro research using primary human hepatocytes validated these results. Lastly, PPAR-α knockout mice retained MBX-102's triglyceride-lowering ability, clearly demonstrating that MBX-102's triglyceride-lowering effect is independent of PPAR-α. Therefore, MBX-102's capacity to lower lipid levels in vivo is mediated by a different mechanism that has not yet been identified.
| Targets |
PPAR-γ
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| ln Vitro |
Arhalofenate (MBX 102) is a prodrug ester that is quickly and entirely changed to the mature free acid form Arhalofenate (MBX 102) acid in vivo by non-specific serum esterases. With EC50s of about 12 μM, arhalofenate (MBX 102) exhibits a dose-dependent activation of mouse GAL4-PPAR-γ[2].
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| ln Vivo |
Arhalofenate (MBX 102) (100 mg/kg, p.o.)decreases hepatic glucose output and increases the rate of glucose infusion significantly during the clamped state in Zucker Diabetic Fatty (ZDF) rats. The insulin resistance index and insulin levels are significantly reduced in response to arhalofenate (MBX 102) (60 mg/kg), both of which cause a dramatic drop in plasma[1]. ZDF rats' triglyceride, free fatty acid, and cholesterol levels are dramatically reduced by arhalofenate (MBX 102) (100 mg/kg, p.o.). Arhalofenate (MBX 102) is an effective antidiabetic agent due to its significant reduction of fasting blood glucose in MBX-102. Moreover, after 32 days of treatment, arhalofenate (MBX 102) (100 mg/kg, p.o.) dramatically reduces fasting plasma insulin and robustly lowers fasting plasma triglycerides in Zucker Fatty (ZF) rats[2].
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| Animal Protocol |
For the assay, 8-week-old male ZDF rats are utilized. ZDF rats live in single-occupancy housing and have unlimited access to food and tap water. Three groups of ZDF rats with comparable mean plasma glucose levels are selected. ZDF rats have their carotid artery and jugular vein cannulated, and they are given at least two days to heal. Rats are given 100 mg/kg of Arhalofenate (MBX 102) or vehicle orally via gavage for a period of 4–7 days. Rats are dosed the day of the clamp experiment, and one hour later, food is removed. Rats are given a 4-hour fast before blood is drawn from the carotid catheter to measure insulin and basal glucose levels. The experiments commence with the injection of 0.5 mL/rat of 5 μCi/mL of d-[3-3H] glucose for priming, followed by a continuous infusion of 8 μCi/mL of d-[3-3H] glucose tracer at a rate of 10 μL/min for 60 minutes. A post-tracer blood sample is taken for measurements of glucose, insulin, and d-[3-3H] glucose specific activity (SA) following the 1-hour tracer-equilibration period. After stopping the tracer glucose infusion, insulin infusion (10 μL/min, or 40 mU/kg/min) is started concurrently with the glucose infusion. Throughout the next 1.5–2 hours, the glucose infusion rate is empirically adjusted to reach a plasma glucose level of 150 mg/dL ± 5%. In order to streamline this procedure, blood samples are drawn at 10-minute intervals so that a glucometer can measure plasma glucose instantly until the study is over. Three consecutive glucose readings that fall inside the previously established range are what constitute a clamp. For the purposes of measuring glucose, insulin, and d-[3-3H] glucose SA, samples (300–400 μL) are taken at three different time points (10-min intervals).
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| References |
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| Molecular Formula |
C19H17CLF3NO4
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| Molecular Weight |
415.79
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| Exact Mass |
415.08
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| Elemental Analysis |
C, 54.89; H, 4.12; Cl, 8.53; F, 13.71; N, 3.37; O, 15.39
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| CAS # |
24136-23-0
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| Related CAS # |
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| Appearance |
Solid powder
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| SMILES |
CC(=O)NCCOC(=O)[C@@H](C1=CC=C(C=C1)Cl)OC2=CC=CC(=C2)C(F)(F)F
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| InChi Key |
BJBCSGQLZQGGIQ-QGZVFWFLSA-N
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| InChi Code |
InChI=1S/C19H17ClF3NO4/c1-12(25)24-9-10-27-18(26)17(13-5-7-15(20)8-6-13)28-16-4-2-3-14(11-16)19(21,22)23/h2-8,11,17H,9-10H2,1H3,(H,24,25)/t17-/m1/s1
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| Chemical Name |
2-acetamidoethyl (2R)-2-(4-chlorophenyl)-2-[3-(trifluoromethyl)phenoxy]acetate
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
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.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] Oral Formulations
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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4051 mL | 12.0253 mL | 24.0506 mL | |
| 5 mM | 0.4810 mL | 2.4051 mL | 4.8101 mL | |
| 10 mM | 0.2405 mL | 1.2025 mL | 2.4051 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.
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.
(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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT01416402 | Completed | Drug: Arhalofenate Drug: Febuxostat |
Hyperuricemia Gout |
CymaBay Therapeutics, Inc. | August 2011 | Phase 2 |
| NCT02063997 | Completed | Drug: Placebo Drug: Colchicine 0.6 mg |
Gout | CymaBay Therapeutics, Inc. | March 2014 | Phase 2 |
| NCT02252835 | Completed | Drug: Arhalofenate Drug: Febuxostat |
Gout Hyperuricemia |
CymaBay Therapeutics, Inc. | August 2014 | Phase 2 |
| NCT01336686 | Completed | Drug: Colchicine Drug: Arhalofenate |
Gout Hyperuricemia |
CymaBay Therapeutics, Inc. | May 2011 | Phase 2 |
| NCT01399008 | Completed | Drug: Arhalofenate Drug: Placebo |
Gout | CymaBay Therapeutics, Inc. | June 2011 | Phase 2 |
 Chemical structures of MBX-102: prodrug ester (panel A) and mature free acid form (panel B). C, Competitive binding assay. D, Reporter assay using a GAL4-PPAR-γ LBD chimera. E and F,Mol Endocrinol.2009 Jul;23(7):975-88. |
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MBX-102 displays insulin sensitization activityin vivo. |
ZF rat study: long-term efficacy (A–D) and side effects (E–H).Mol Endocrinol.2009 Jul;23(7):975-88. |
 Effect of MBX-102 acid on osteoblast/adipocyte differentiation pathways in murine C3H10T1/2 mesenchymal stem cells. |
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A, LPS-induced MCP-1, IL-6, IL-1β, and IL12p40-secreted cytokine levels. B, WT or PPAR-γ −/− (KO) primary mouse macrophages.Mol Endocrinol.2009 Jul;23(7):975-88. |
 Correlation between the transactivation and transrepression potential of several PPAR-γ (SP1, SP2, rosiglitazone, pioglitazone, troglitazone, and MBX-102 acid) and dual PPAR-α/γ (tesaglitazar and muraglitazar) agonists. The transactivation profile of each compound was assessed by measuring FABP4 gene induction and was plotted as fold change (FC)vs. the DMSO-treated control group. |
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