| Size | Price | Stock | Qty |
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| Targets |
PPARγ
FX-909 targets peroxisome proliferator-activated receptor gamma (PPARγ), functioning as a covalent inverse agonist. PPARγ is a nuclear receptor involved in adipocyte differentiation, glucose metabolism, and inflammation, and has been implicated in various cancers. FX-909 binds covalently to PPARγ and stabilizes the ligand-binding domain in a transcriptionally repressive conformation. This inverse agonist activity results in the inhibition of PPARγ-mediated transcription. The compound exhibits more potent co-repressor-selective inverse agonism compared to T0070907. It is being developed for advanced solid malignancies, particularly urothelial carcinoma. |
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| ln Vitro |
In vitro, FX-909 demonstrates potent PPARγ inverse agonist activity. Functional profiling and NMR studies show that FX-909 exhibits more potent co-repressor-selective inverse agonism and more effectively stabilizes the PPARγ ligand-binding domain in a transcriptionally repressive conformation compared to T0070907. The compound's activity is assessed in cell-based reporter assays using PPARγ response element (PPRE)-luciferase constructs. Its covalent binding mechanism is confirmed through biochemical assays. FX-909 shows antitumor activity in preclinical models.
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| ln Vivo |
In a UMUC9 UC xenograft mouse model, FX-909 (0.03-1 mg/kg; BID for 21 days) has anti-cancer properties [1].
In vivo, FX-909 demonstrates antitumor activity. At doses of 0.03-1 mg/kg administered twice daily for 21 days, FX-909 shows anticancer effects in UMUC9 UC xenograft mouse models. The compound is being developed for advanced solid malignancies, particularly urothelial carcinoma. Its oral bioavailability supports convenient dosing regimens. Further studies are needed to fully characterize its efficacy across different tumor types and in combination with other therapeutic agents. The compound's inverse agonist mechanism may offer advantages over traditional PPARγ agonists. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for FX-909 typically involve covalent binding studies using PPARγ protein. The compound's binding to PPARγ is assessed using biochemical assays that measure covalent modification of the receptor. Functional assays using PPRE-luciferase reporter constructs in cell-based systems evaluate the compound's inverse agonist activity. The compound's ability to stabilize the PPARγ LBD in a repressive conformation is confirmed through NMR studies. Assays are conducted under appropriate conditions with proper controls.
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| Cell Assay |
In vitro cell-based assays for FX-909 utilize cell lines expressing PPARγ to assess its inverse agonist activity. Cells are treated with varying concentrations of the compound for 24-48 hours. PPARγ-mediated transcriptional activity is evaluated using reporter gene assays with PPRE-luciferase constructs. The compound's inverse agonist activity is assessed by its ability to repress basal PPARγ transcriptional activity and inhibit agonist-induced activation. Covalent binding is confirmed through washout experiments or mass spectrometry. Standard cell culture conditions (37°C, 5% CO₂) with appropriate media are employed.
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| Animal Protocol |
In vivo animal studies with FX-909 typically involve administration of the compound to immunocompromised mice bearing urothelial carcinoma xenografts. The compound is administered orally at doses of 0.03-1 mg/kg twice daily for 21 days. Endpoints include tumor volume measurements, assessment of PPARγ target gene expression in tumor tissues, evaluation of biomarkers of antitumor activity, and pharmacokinetic profiling. The compound demonstrates significant antitumor effects in these models. All procedures must comply with institutional animal care and use guidelines.
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| ADME/Pharmacokinetics |
FX-909 is orally bioavailable. It has a molecular weight of 360.33 g/mol and a molecular formula of C₁₇H₁₀F₂N₂O₃S. Its chemical name is 3-(5,7-difluoro-4-oxo-1H-quinolin-2-yl)-4-methylsulfonylbenzonitrile. As a covalent inverse agonist, its pharmacokinetic properties are influenced by the kinetics of covalent binding to the target. The compound is typically stored at -20°C. Detailed PK parameters including half-life, Cmax, and AUC are available from preclinical studies.
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| Toxicity/Toxicokinetics |
FX-909 is intended for research use only and is not approved for human therapeutic applications. As a research chemical, comprehensive toxicological data are not extensively documented in the publicly accessible literature. Standard safety precautions should be observed when handling this compound, including the use of appropriate personal protective equipment. As with all research chemicals, comprehensive toxicological profiling would be required before any consideration for clinical development.
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| References | |
| Additional Infomation |
The PPARγ inhibitor FX-909 is an orally administered peroxisome proliferator-activated receptor γ (PPARγ; PPARG) inverse agonist and inhibitor with potential antitumor activity. After oral administration, the PPARG inhibitor FX-909 selectively targets and covalently binds to a region on PPARG isolated from mutation sites. This binding promotes the formation of an inhibitory conformation of PPARG and inhibits its activity. This inhibits basal transcription and ligand-activated transcription of PPARG and blocks the transcription of PPARG-mediated target genes such as FABP4/Fabp4, AGT/Agt, IVT/Ivd, and ARG1/Arg1. This may inhibit the proliferation of tumor cells with excessive PPARG activation. PPARG is a nuclear receptor whose genes are altered in certain tumor cells associated with luminal lineage subtypes, including amplification, missense mutations, and fusions.
FX-909 (CAS#: 2924573-90-8) has a molecular formula of C₁₇H₁₀F₂N₂O₃S and a molecular weight of 360.33 g/mol. Its chemical name is 3-(5,7-difluoro-4-oxo-1H-quinolin-2-yl)-4-methylsulfonylbenzonitrile. It is a first-in-class, orally bioavailable, covalent PPARγ inverse agonist. FX-909 exhibits more potent co-repressor-selective inverse agonism compared to T0070907. It is developed for advanced solid malignancies, particularly urothelial carcinoma. FX-909 shows antitumor activity in vivo. This compound is not a drug and has not undergone clinical trials. |
| Molecular Formula |
C17H10F2N2O3S
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| Molecular Weight |
360.334709644318
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| Exact Mass |
360.038
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| CAS # |
2924573-90-8
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| PubChem CID |
167993670
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| Appearance |
White to off-white solid powder
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| LogP |
2.4
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
25
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| Complexity |
737
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1(F)C=C2C(=C(F)C=1)C(=O)C=C(C1=C(C=CC(C#N)=C1)S(=O)(=O)C)N2
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| InChi Key |
RBUBBZVQPHSZEZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H10F2N2O3S/c1-25(23,24)16-3-2-9(8-20)4-11(16)13-7-15(22)17-12(19)5-10(18)6-14(17)21-13/h2-7H,1H3,(H,21,22)
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| Chemical Name |
3-(5,7-difluoro-4-oxo-1H-quinolin-2-yl)-4-methylsulfonylbenzonitrile
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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 |
| 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) |
DMSO: 100 mg/mL (277.52 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.94 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 | 2.7752 mL | 13.8762 mL | 27.7523 mL | |
| 5 mM | 0.5550 mL | 2.7752 mL | 5.5505 mL | |
| 10 mM | 0.2775 mL | 1.3876 mL | 2.7752 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.
Link: https://clinicaltrials.gov/ct2/show/NCT05929235
Conditions:Advanced Urothelial Carcinoma|Oral Drug Administration|Open LabelProducts are for research use only; We do not sell to patients
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