| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| Other Sizes |
| Targets |
ADAR1/RNA adenosine deaminase 1
The primary target is RNA adenosine deaminase 1 (ADAR1), an enzyme involved in RNA editing. ADAR1 catalyzes the conversion of adenosine (A) to inosine (I) in double-stranded RNA, a process that affects gene expression and can promote cancer survival and immune evasion. By inhibiting ADAR1, Fludarabine-Cl disrupts these processes. It is a selective ADAR1 inhibitor with an IC50 of 0.87 microM. It can be used for preventing or treating cancer or tumor-related diseases. |
|---|---|
| ln Vitro |
Fludarabine-Cl has potent inhibitory effects on RNA adenosine deaminase 1 (ADAR1), and can be used to prevent and/or treat cancer or tumor related diseases caused by abnormal activity of this enzyme, especially prostate cancer, leukemia, breast cancer, multiple myeloma, lung cancer, stomach cancer, ovarian cancer, colon cancer, liver cancer, pancreatic cancer.
Fludarabine-Cl shows inhibition effect on ADAR1 with an IC50 of 0.87 microM. It is a chemotherapy drug used primarily for the treatment of hematologic cancers such as chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma. It is a potent and selective ADAR1 inhibitor that can be used for preventing and/or treating cancer-related diseases. |
| ln Vivo |
Fludarabine-Cl is a chemotherapy drug used primarily in the treatment of hematologic cancers such as chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma. It can be used in animal models of cancer to demonstrate dose-dependent reduction of tumor burden. ADAR1 inhibition is a key mechanism for its anti-leukemic effects. It is studied in vivo to assess its ability to overcome drug resistance.
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| Enzyme Assay |
For a cell-free biochemical assay, recombinant human ADAR1 protein (e.g., p150 isoform, 0.1-1 uM) is incubated with a 32P-labeled double-stranded RNA substrate and varying concentrations of Fludarabine-Cl (0.01-10 uM) in a reaction buffer (50 mM Tris-HCl pH 7.5, 100 mM NaCl, 5 mM EDTA, 1 mM DTT, 10% glycerol). After incubation at 37degC for 60-120 minutes, the RNA is purified and hydrolyzed to nucleosides. The conversion of adenosine to inosine is measured by HPLC or LC-MS/MS. The IC50 of 0.87 uM is calculated from the reduction in inosine formation.
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| Cell Assay |
For in vitro cell-based assays, cancer cell lines (e.g., CLL, K562, MV-4-11) are seeded in 96-well plates. Cells are treated with Fludarabine-Cl at concentrations ranging from 0.01 to 10 uM for 48-72 hours. Cell viability is measured using CellTiter-Glo assay. To assess ADAR1 inhibition, total RNA is extracted from treated cells. The extent of A-to-I RNA editing at known ADAR1 target sites (e.g., AZIN1, FLNA) is quantified by Sanger sequencing or high-throughput sequencing comparing treated vs. control samples. For Western blot, ADAR1 protein levels may also be measured.
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| Animal Protocol |
For in vivo efficacy studies, xenograft models of CLL or AML are established in immunocompromised mice (e.g., NSG mice injected with MOLT-4 or K562 cells). Once the tumor burden is established, mice are administered Fludarabine-Cl intravenously (IV) or intraperitoneally (IP) at a dose of 25-50 mg/kg daily for 5 days. Tumor growth is monitored by bioluminescence imaging (if cells are labeled with luciferase) or by measuring tumor volume. Blood samples are collected to assess white blood cell counts and measure plasma drug levels by LC-MS/MS. At the endpoint, RNA is extracted from tumor tissues to measure editing levels at ADAR1 target sites.
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| ADME/Pharmacokinetics |
Fludarabine-Cl (MW: 303.68, Formula: C10H11ClFN5O3) is a small-molecule nucleoside analog. It is soluble in DMSO and exhibits good stability when stored at -20degC (3 years powder, 6 months in solution). As a chemotherapy drug, it is designed to be administered intravenously. Its chlorinated structure may alter its metabolic stability compared to the parent compound Fludarabine.
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| Toxicity/Toxicokinetics |
As a nucleoside analog chemotherapy drug, it has the potential for myelosuppression (bone marrow suppression) and immunosuppression. It is cytotoxic to rapidly dividing cells. It should be handled as a hazardous chemical using appropriate containment (fume hood) and personal protective equipment (gloves, lab coat, eye protection). It is for research use only and is not to be used in humans outside of approved clinical protocols.
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| References | |
| Additional Infomation |
Fludarabine-Cl is a highly potent ADAR1 inhibitor with potential to be developed as a therapeutic for hematological malignancies, particularly those that are resistant to conventional therapies. It is a potent, selective, and orally available phosphomannose isomerase (PMI) inhibitor with an IC50 of 1.3 microM. ML089 can be used for the research of congenital disorder of glycosylation Ia.
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| Molecular Formula |
C10H11CLFN5O3
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|---|---|
| Molecular Weight |
303.677443742752
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| Exact Mass |
303.053
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| CAS # |
2734853-80-4
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| PubChem CID |
162354766
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| Appearance |
Typically exists as White to off-white solids at room temperature
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| LogP |
0.1
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
20
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| Complexity |
370
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| Defined Atom Stereocenter Count |
4
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| SMILES |
C1=NC2=C(N=C(N=C2N1[C@H]3[C@@H]([C@@H]([C@H](O3)CCl)O)O)F)N
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| InChi Key |
HSCKXTNMVCTWGY-UUOKFMHZSA-N
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| InChi Code |
InChI=1S/C10H11ClFN5O3/c11-1-3-5(18)6(19)9(20-3)17-2-14-4-7(13)15-10(12)16-8(4)17/h2-3,5-6,9,18-19H,1H2,(H2,13,15,16)/t3-,5-,6-,9-/m1/s1
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| Chemical Name |
(2R,3R,4S,5S)-2-(6-amino-2-fluoropurin-9-yl)-5-(chloromethyl)oxolane-3,4-diol
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| Synonyms |
Fludarabine-Cl; 2734853-80-4; Fludarabine-Cl?; SCHEMBL24981041; MS-24385;
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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) |
H2O : ~5 mg/mL (~16.46 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2 mg/mL (6.59 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.2929 mL | 16.4647 mL | 32.9294 mL | |
| 5 mM | 0.6586 mL | 3.2929 mL | 6.5859 mL | |
| 10 mM | 0.3293 mL | 1.6465 mL | 3.2929 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.
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