Casdatifan
Based on 1 Customer Validation
Casdatifan (AB521) is an orally active and selective allosteric small-molecule inhibitor of hypoxia-inducible factor 2α (HIF-2α). Casdatifan inhibits pro-tumor gene transcription by blocking the heterodimerization of HIF-2α with ARNT, and significantly suppresses tumor growth in clear cell renal cell carcinoma (ccRCC) models either as a monotherapy or in combination with agents such as Zimberelimab (HY-P99109). Casdatifan is applicable for the research of ccRCC.
For research use only. We do not sell to patients.
- Purity : 96.37%
- CAS No.: 2709069-30-5
- Formula: C21H17F4NO3S
- Molecular Weight:439.42
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Storage: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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Biological Activity
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Chemical Information
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Solvent & Solubility
- Protocols
- Purity & Documentation
- References
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Help & FAQs
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Biological Activity
Description
In Vitro
Casdatifan (2-10 μM; 24 h) reduces HIF-2α protein levels in 786-O and A-498 clear cell renal cell carcinoma (ccRCC) cells under normoxic conditions[1].
Casdatifan potently inhibits VEGF secretion in 786-O ccRCC cells, with an IC50 of 28.9 nM[1].
Casdatifan (0.001-10 μM; 21 days) inhibits the anchorage-independent growth of 786-O ccRCC cells in a concentration-dependent manner[1].
Casdatifan (1 μM; 20 h) inhibits HIF-2α-dependent gene transcription in hypoxically induced primary human M2-polarized macrophages[1].
Casdatifan (3 days) reduces HIF-2α protein levels in activated hypoxic primary human CD8+ T cells without impairing T cell proliferation or cytokine secretion[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:786-O and A-498 cells
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Concentration:2, 10 μM
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Incubation Time:24 h
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Result:Caused a marked reduction in HIF-2α protein levels in both 786-O and A-498 cells.
In Vivo
Casdatifan (30 mg/kg; p.o.; once daily; until study endpoint) significantly enhances the antitumor efficacy in the NSG-MHC I/II DKO humanized PBMC A-498 ccRCC xenograft model when administered in combination with Zimberelimab (HY-P99109)[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NU-Foxn1nu nude mice (female, 6-8 weeks old, subcutaneous xenograft of 786-O or A-498 cells)[1]
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Dosage:3 mg/kg; 10 mg/kg; 30 mg/kg; 100 mg/kg
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Administration:p.o.; daily; until the end of the study
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Result:Significantly reduced tumour burden in both 786-O and A-498 models.
Decreased HIF-2α protein levels and tumour cell proliferation (Ki-67 staining), and downregulated HIF-2α target genes (VEGFA, CCND1, CXCR4) in tumour tissues in a dose-dependent manner.
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Animal Model:NSG-MHC I/II DKO (female, 4-5 weeks old, humanized PBMC A-498 xenograft model)[1]
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Dosage:30 mg/kg
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Administration:p.o.; daily; until the end of the study
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Result:Led to more rapid and sustained tumour regression than either monotherapy, with 60% of mice achieving a complete response after treatment cessation.
Induced considerable tumour regression but growth resumed after treatment stop until the end of the study, while Zimberelimab alone showed modest efficacy.
Chemical Information
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CAS No. 2709069-30-5
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Appearance Solid
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Molecular Weight 439.42
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Formula C21H17F4NO3S
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Color White to off-white
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SMILES
CS(C(C1=C2C[C@@H](F)[C@H]1O)=CC=C2[C@](C[C@H](F)[C@@H]3F)([H])C4=C3C=C(F)C=C4C#N)(=O)=O
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Synonyms
AB521
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvent & Solubility
In Vitro:
DMSO : 100 mg/mL (227.57 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.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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 (5.69 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 (5.69 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.
Protocols
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Patient-Derived Xenograft (PDX)
Patient-derived xenograft (PDX) models are generated by engrafting primary human tumor tissue directly into immunodeficient mice, allowing in vivo propagation of patient tumor biology without initial in vitro adaptation. These models are used to preserve key histopathological and molecular characteristics of the original tumor and enable assessment of tumor growth dynamics and therapeutic response in a living organism. The biological readout is tumor engraftment and subsequent growth in the murine host, which reflects the ability of human tumor cells to survive, vascularize, and expand in an immunocompromised microenvironment.
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Patient-Derived Orthotopic Xenograft (PDOX)
Patient-derived orthotopic xenograft (PDOX) modeling implants fresh patient tumor tissue or patient-derived tumor cells into the anatomically corresponding organ or tissue site of immunodeficient mice, usually by surgical orthotopic implantation, to preserve patient tumor histology, local microenvironmental context, invasion, metastatic behavior, and treatment-response features better than subcutaneous implantation. PDOX readouts include tumor engraftment, orthotopic tumor growth, local invasion, metastasis, recurrence after resection, histologic similarity to the donor tumor, biomarker retention, molecular concordance, survival, and response or resistance to therapy. PDOX models are used for preclinical drug testing and individualized therapy evaluation, but engraftment success varies by tumor type and specimen quality.
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Subcutaneous Cell-Line-Derived Xenograft
Subcutaneous cell-line-derived xenograft (CDX) models are established by implanting cultured human cancer cell lines into immunodeficient mice, where the injected cells form localized tumors that can be monitored in vivo as a measure of tumorigenic potential, growth kinetics, and treatment response. These models are widely used in oncology research because they allow reproducible tumor formation and enable comparative assessment of tumor growth between different cell lines or genetic manipulations in a controlled in vivo microenvironment. Subcutaneous implantation of cancer cells in immunodeficient mice is a standard approach for evaluating tumor growth behavior and therapeutic response across multiple cancer types, including prostate, esophageal, pancreatic, and colon cancer models.
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Orthotopic Cell-Line Xenograft
Orthotopic cell-line xenograft models involve implantation of human cancer cell lines into the anatomically corresponding organ of immunodeficient mice to reproduce tumor growth within a native microenvironment, enabling more clinically relevant tumor behavior compared with subcutaneous models. These models are widely used because orthotopic placement better recapitulates tumor progression, including invasion and metastatic spread, which are often underrepresented in heterotopic implantation systems. Compared with conventional xenografts, orthotopic implantation is described as more technically complex but provides improved simulation of tumor-microenvironment interactions and metastatic behavior, making it particularly valuable for translational oncology research. Surgical orthotopic implantation approaches have been emphasized as enabling faithful reproduction of clinical cancer features, including metastasis and disease progression patterns that align with the tumor’s organ of origi
Purity & Documentation
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Data Sheet (283 KB)
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SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Korean - KR (251 KB)
- Portuguese - PT (251 KB)
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Handling Instructions (2659 KB)
References
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 | 2.2757 mL | 11.3786 mL | 22.7573 mL | 56.8932 mL |
| 5 mM | 0.4551 mL | 2.2757 mL | 4.5515 mL | 11.3786 mL | |
| 10 mM | 0.2276 mL | 1.1379 mL | 2.2757 mL | 5.6893 mL | |
| 15 mM | 0.1517 mL | 0.7586 mL | 1.5172 mL | 3.7929 mL | |
| 20 mM | 0.1138 mL | 0.5689 mL | 1.1379 mL | 2.8447 mL | |
| 25 mM | 0.0910 mL | 0.4551 mL | 0.9103 mL | 2.2757 mL | |
| 30 mM | 0.0759 mL | 0.3793 mL | 0.7586 mL | 1.8964 mL | |
| 40 mM | 0.0569 mL | 0.2845 mL | 0.5689 mL | 1.4223 mL | |
| 50 mM | 0.0455 mL | 0.2276 mL | 0.4551 mL | 1.1379 mL | |
| 60 mM | 0.0379 mL | 0.1896 mL | 0.3793 mL | 0.9482 mL | |
| 80 mM | 0.0284 mL | 0.1422 mL | 0.2845 mL | 0.7112 mL | |
| 100 mM | 0.0228 mL | 0.1138 mL | 0.2276 mL | 0.5689 mL |
Casdatifan Related Classifications
HY-159644 Related Classifications
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