Rabacfosadine
Based on 1 Customer Validation
Rabacfosadine (GS-9219), a novel proagent of the nucleotide analogue PMEG, is designed as a cytotoxic agent that preferentially targets lymphoid cells.
Nur für Forschungszwecke. Wir verkaufen nicht an Patienten.
- Reinheit: 98.45%
- CAS. Nr.: 859209-74-8
- Formel: C21H35N8O6P
- Molecular Weight:526.53
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Speicherung:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
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Biologische Aktivität
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Chemical Information
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Lösungsmittel & Löslichkeit
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Biologische Aktivität
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| CCRF-CEM | IC50 |
0.48 μM
Compound: 2, GS-9219
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Antiproliferative activity against human CCRF-CEM after 72 hrs by XTT assay
Antiproliferative activity against human CCRF-CEM after 72 hrs by XTT assay
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[PMID: 21664011] |
| HeLa S3 | IC50 |
2.15 μM
Compound: 2, GS-9219
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Antiproliferative activity against human HeLaS3 after 72 hrs by XTT assay
Antiproliferative activity against human HeLaS3 after 72 hrs by XTT assay
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[PMID: 21664011] |
| HL-60 | IC50 |
0.78 μM
Compound: 2, GS-9219
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Antiproliferative activity against human HL60 after 72 hrs by XTT assay
Antiproliferative activity against human HL60 after 72 hrs by XTT assay
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[PMID: 21664011] |
In lymphocytes, Rabacfosadine (GS-9219) is converted to its active metabolite, 9-(2-phosphonylmethoxyethyl)guanine (PMEG) diphosphate, via enzymatic hydrolysis, deamination, and phosphorylation. GS-9219 has substantial antiproliferative activity against activated lymphocytes and hematopoietic tumor cell lines. The ability of Rabacfosadine to inhibit the proliferation of activated lymphocytes and of tumor cells of hematopoietic origin is investigated. Rabacfosadine inhibits the proliferation of mitogen-stimulated T and B lymphocytes with EC50 values of 135 and 42 nM, respectively, as determined by BrdUrd incorporation. To compare the activity of GS-9219 in dividing and nondividing cells, Rabacfosadine is evaluated in these populations using a metabolism-based sodium XTT assay instead of BrdUrd assays. Results from the XTT assay shows a 127-fold difference between the EC50 values of Rabacfosadine in quiescent (EC50=17.2 μM) and proliferating (EC50=135 nM) cells. These results indicate a substantial selectivity of Rabacfosadine toward actively replicating lymphoblasts[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS. Nr. 859209-74-8
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Appearance Solid
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Molecular Weight 526.53
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Formel C21H35N8O6P
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Color Light yellow to yellow
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SMILES
CCOC([C@H](C)NP(N[C@@H](C)C(OCC)=O)(COCCN1C=NC2=C(NC3CC3)N=C(N)N=C12)=O)=O
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Synonyms
GS-9219; VDC-1101
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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
DMSO : 100 mg/mL (189.92 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)
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 (4.75 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 (4.75 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.
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
Twenty million PHA-stimulated T cells are incubated with 10 μM[14C]GS-9219 for 24 h. Cells are washed once with tissue culture medium and twice with PBS, incubated in 80% methanol overnight, and centrifuged at 14,000 rpm for 15 min to remove denatured proteins. The methanol extracts are lyophilized and dissolved in the high-performance liquid chromatography (HPLC) loading buffer. A portion of each sample is used for scintillation counting to calculate the total pmoles, and the rest is used for HPLC analysis to calculate the ratio of metabolites. HPLC analysis is done by gradient elution using a Phenomenex Prodigy column (5 μm, ODS3 150×4 mm), where buffer A is 25 mM K2HPO4 (pH 6.0) and 5 mM Tetrabutylammonium bromide and buffer B is 25 mM K2HPO4 (pH 6.0), 70% Acetonitrile, and 5 mM Tetrabutylammonium bromide[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Dogs[2]
Dogs are given alternating doses of Rabacfosadine and Doxorubicin every 3 weeks. Rabacfosadine is administered at a dosage of 1.0 mg/kg as a 30-minute IV infusion on weeks 0, 6, and 12. Doxorubicin is administered at a dosage of 30 mg/m2 (1.0 mg/kg for dogs weighing <15 kg) as an approximately 20-minute IV infusion on weeks 3, 9, and 15. Concurrent cytotoxic chemotherapy of any kind and concurrent corticosteroids are not allowed. A CBC is performed 1 week after the first Rabacfosadine and Doxorubicin treatments (weeks 1 and 4). All dogs have a physical examination with lymph node measurements, owner history, CBC, serum biochemistry profile (SBC), and urinalysis performed at each chemotherapy visit. Thoracic radiographs are recommended at week 15 and approximately every 2 months thereafter in responding dogs. Dose delays, reductions, or both, and supportive treatment for AEs are carried out at the discretion of the attending clinician. Dogs that experienced a complete response (CR) are followed with monthly physical examinations after week 15 until relapse, when they are considered off study. Dogs that experienced partial response (PR) or stable disease (SD) at week 15 are considered off study and censored from analysis at that time. At the time of study withdrawal, dogs are eligible for additional treatment at the discretion of the attending clinician.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Reinheit & Dokumentation
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Data Sheet (283 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
[1]. Reiser H, et al. GS-9219--a novel acyclic nucleotide analogue with potent antineoplastic activity in dogs with spontaneous non-Hodgkin's lymphoma. Clin Cancer Res. 2008 May 1;14(9):2824-32. [Content Brief]
[2]. Thamm DH, et al. Alternating Rabacfosadine/Doxorubicin: Efficacy and Tolerability in Na?ve Canine Multicentric Lymphoma. J Vet Intern Med. 2017 May;31(3):872-878. [Content Brief]
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 |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.8992 mL | 9.4961 mL | 18.9923 mL | 47.4807 mL |
| 5 mM | 0.3798 mL | 1.8992 mL | 3.7985 mL | 9.4961 mL | |
| 10 mM | 0.1899 mL | 0.9496 mL | 1.8992 mL | 4.7481 mL | |
| 15 mM | 0.1266 mL | 0.6331 mL | 1.2662 mL | 3.1654 mL | |
| 20 mM | 0.0950 mL | 0.4748 mL | 0.9496 mL | 2.3740 mL | |
| 25 mM | 0.0760 mL | 0.3798 mL | 0.7597 mL | 1.8992 mL | |
| 30 mM | 0.0633 mL | 0.3165 mL | 0.6331 mL | 1.5827 mL | |
| 40 mM | 0.0475 mL | 0.2374 mL | 0.4748 mL | 1.1870 mL | |
| 50 mM | 0.0380 mL | 0.1899 mL | 0.3798 mL | 0.9496 mL | |
| 60 mM | 0.0317 mL | 0.1583 mL | 0.3165 mL | 0.7913 mL | |
| 80 mM | 0.0237 mL | 0.1187 mL | 0.2374 mL | 0.5935 mL | |
| 100 mM | 0.0190 mL | 0.0950 mL | 0.1899 mL | 0.4748 mL |
Rabacfosadine Related Classifications
HY-13640 Related Classifications
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