FORX-428
Based on 1 Customer Validation
FORX-428 is an orally active, selective poly (ADP-ribose) glycohydrolase (PARG) inhibitor. FORX-428 reversibly inhibits PARG, thereby blocking PAR chain dissociation, inhibiting DNA repair, inducing tumor cell death, and targeting replication stress in cancer cells. FORX-428 can be used in the research of ovarian cancer and triple-negative breast cancer.
Nur für Forschungszwecke. Wir verkaufen nicht an Patienten.
- Reinheit : 98.31%
- CAS. Nr.: 2922789-15-7
- Formel: C20H25F2N7O2S2
- Molecular Weight:497.59
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Speicherung:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biologische Aktivität
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Chemical Information
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Lösungsmittel & Löslichkeit
- Protokoll
- Reinheit & Dokumentation
- Verweise
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Help & FAQs
Biologische Aktivität
Beschreibung
Cellular Effect
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Cell Line
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Type | Value | Description | References |
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| MDA-MB-436 | IC50 |
19 nM
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Inhibition of viability of human MDA-MB-436 triple-negative breast cancer cells by cell viability assay.
Inhibition of viability of human MDA-MB-436 triple-negative breast cancer cells by cell viability assay.
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EORTC_NCI_AACR-2025-poster_FORX-428_final_10072025.pdf |
| HCC1937 | IC50 |
17 nM
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Inhibition of viability of human HCC1937 breast cancer cells by cell viability assay.
Inhibition of viability of human HCC1937 breast cancer cells by cell viability assay.
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EORTC_NCI_AACR-2025-poster_FORX-428_final_10072025.pdf |
| KURAMOCHI | IC50 |
0.6 nM
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Inhibition of viability of human Kuramochi ovarian cancer cells by cell viability assay.
Inhibition of viability of human Kuramochi ovarian cancer cells by cell viability assay.
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EORTC_NCI_AACR-2025-poster_FORX-428_final_10072025.pdf |
| U2OS | IC50 |
>5000 nM
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Inhibition of viability of human U2OS osteosarcoma cells by cell viability assay.
Inhibition of viability of human U2OS osteosarcoma cells by cell viability assay.
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EORTC_NCI_AACR-2025-poster_FORX-428_final_10072025.pdf |
In Vitro
FORX-428 potently inhibits purified PARG, with a Kd value of 0.3 nM, an IC50 value of 0.06 nM, and a target residence time as long as 104 minutes[1].
FORX-428 inhibits the proliferation of MDA-MB-436 (IC50 = 19 nM), HCC1937 (IC50 = 17 nM), HCC1428 (IC50 = 1.7 nM), RMUG-S (IC50 < 0.5 nM), and Kuramochi (IC50 = 0.6 nM) cells, but exerts no potent inhibitory effect on the viability of U2OS cells, with an IC50 greater than 5000 nM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
In Vivo
FORX-428 (once daily; oral administration; for approximately 20 days) exerts a significant tumor growth inhibitory effect in a triple-negative breast cancer model (MDA-MB-436; HRD+; acquired resistance to PARP inhibitors)[1].
FORX-428 (10 mg/kg or 100 mg/kg; once daily; p.o.; 120 days) induces long-lasting tumor regression and sustains tumor control after discontinuation in a PARP inhibitor-resistant ovarian cancer PDX model harboring BRCA1 revertant mutations[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Derived ovarian cancer tumor tissues carrying a BRCA1 reversion mutation were subcutaneously implanted into immunodeficient mice to establish a PDX model. This model was confirmed to be resistant to Olaparib (a PARPi)[1]
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Dosage:10 mg/kg ; 100 mg/kg
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Administration:p.o.; once daily; total observation period of up to 120 days, including phases of treatment cessation and rechallenge
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Result:Animals in both the 10 mg/kg and 100 mg/kg dose groups displayed profound tumor regression.
Animals maintained sustained tumor inhibition during the treatment cessation phase and effectively controlled tumor volume upon restarting therapy, whereas animals treated with 100 mg/kg Olaparib exhibited uncontrolled tumor growth.
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS. Nr. 2922789-15-7
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Appearance Solid
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Molecular Weight 497.59
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Formel C20H25F2N7O2S2
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Color Light yellow to yellow
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SMILES
CC1(CC1)NS(=O)(C2=CN3C(C(N4C[C@@H](N[C@H](C4)C)C)=C2)=CN=C3C5=NN=C(C(F)F)S5)=O
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Versand
Room temperature in continental US; may vary elsewhere.
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Speicherung
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Lösungsmittel & Löslichkeit
In Vitro:
DMSO : 100 mg/mL (200.97 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (5.02 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (5.02 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Protokoll
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Mammalian live/dead viability and cytotoxicity staining
Live/dead viability and cytotoxicity staining assays are based on the simultaneous detection of intracellular esterase activity in metabolically active (viable) cells and membrane integrity loss in non-viable cells. In commonly used dual-staining approaches, membrane-permeant fluorogenic substrates are converted by intracellular esterases into fluorescent products in live cells, while impermeant DNA-binding dyes selectively enter cells with compromised plasma membranes and label nucleic acids in dead or dying cells, enabling discrimination between viable and non-viable populations by fluorescence microscopy or flow cytometry.
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Apoptosis Solutions
Apoptosis is a regulated, generally non-lytic cell-death pathway that removes unwanted, damaged, infected, or abnormal cells through coordinated morphological changes, caspase activation, DNA fragmentation, and membrane remodeling. The intrinsic apoptosis pathway is controlled mainly by mitochondrial outer membrane permeabilization, BCL-2 family proteins, cytochrome c release, apoptosome formation, caspase-9 activation, and downstream executioner caspase-3/7 activation. The extrinsic apoptosis pathway is initiated by death receptors such as Fas, TNFR, and TRAIL receptors, which recruit adaptor proteins and activate caspase-8 before engaging executioner caspases or mitochondrial amplification through BID cleavage. Apoptosis is linked to many phenotypes, including cancer cell killing, tissue homeostasis, immune regulation, neurodegeneration, infection response, and treatment-induced cytotoxicity; unresolved questions include how apoptosis interacts with necroptosis, pyroptosis, ferroptos
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Breast Cancer Modeling
Breast cancer is a heterogeneous cancer, and it has been distinguished into four subtypes: luminal A, luminal B, HER2-positive and basal-like. Molecular mutations, epigenetic alterations, hormone exposure and immune microenvironment are related to the progression of breast cancer.
Reinheit & Dokumentation
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Data Sheet (278 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Handling Instructions (2659 KB)
Verweise
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
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| DMSO | 1 mM | 2.0097 mL | 10.0484 mL | 20.0969 mL | 50.2422 mL |
| 5 mM | 0.4019 mL | 2.0097 mL | 4.0194 mL | 10.0484 mL | |
| 10 mM | 0.2010 mL | 1.0048 mL | 2.0097 mL | 5.0242 mL | |
| 15 mM | 0.1340 mL | 0.6699 mL | 1.3398 mL | 3.3495 mL | |
| 20 mM | 0.1005 mL | 0.5024 mL | 1.0048 mL | 2.5121 mL | |
| 25 mM | 0.0804 mL | 0.4019 mL | 0.8039 mL | 2.0097 mL | |
| 30 mM | 0.0670 mL | 0.3349 mL | 0.6699 mL | 1.6747 mL | |
| 40 mM | 0.0502 mL | 0.2512 mL | 0.5024 mL | 1.2561 mL | |
| 50 mM | 0.0402 mL | 0.2010 mL | 0.4019 mL | 1.0048 mL | |
| 60 mM | 0.0335 mL | 0.1675 mL | 0.3349 mL | 0.8374 mL | |
| 80 mM | 0.0251 mL | 0.1256 mL | 0.2512 mL | 0.6280 mL | |
| 100 mM | 0.0201 mL | 0.1005 mL | 0.2010 mL | 0.5024 mL |
FORX-428 Related Classifications
HY-164717 Related Classifications
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