| Size | Price | Stock | Qty |
|---|---|---|---|
| 100mg |
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| 1g | |||
| Other Sizes |
| Targets |
CD73-IN-4 targets CD73 (cluster of differentiation 73), a cell surface enzyme that catalyzes the conversion of extracellular adenosine monophosphate (AMP) to adenosine. In the tumor microenvironment, elevated adenosine levels suppress the activity of immune cells, including T-cells and NK cells. By inhibiting CD73, CD73-IN-4 prevents the production of immunosuppressive adenosine, thereby relieving this suppression and potentially improving responses to immunotherapies.
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|---|---|
| ln Vitro |
CHO overexpressing hCD73 (IC50 = 2.6 nM) or mCD73 (IC50 = 13) cells demonstrated good potency nM) and the human ovarian cancer cell line SKOV-3 (IC50 = 0.55 nM). CD73-IN-4 (Compound 4a) on soluble hCD73 (IC50 = 0.86 nM) and soluble mouse CD73 (mCD73; IC50 = 3.0 nM). For CD39, A2aR, and NTPDase2, 3 and 8 (IC50 > 10 000 nM), it demonstrates exceptional selectivity [1].
In vitro, CD73-IN-4 is a potent and selective inhibitor of human CD73 with an IC50 of 2.6 nM. It shows potent inhibitory bioactivity on human C-terminal His6-tagged CD73 with an IC50 of 11.0 nM and significant inhibition of CD73 in human SK-OV-3 cells with an IC50 of 3.0 nM. Its activity is measured in enzymatic assays using recombinant CD73. |
| ln Vivo |
In vivo, CD73-IN-4 is used to study the role of CD73 in cancer immunology. By reducing adenosine production, it can enhance anti-tumor immune responses. Its potential to improve responses to immunotherapies makes it a compound of interest for combination strategies.
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| Enzyme Assay |
The inhibitory activity of CD73-IN-4 is assessed using in vitro enzyme assays. Recombinant human CD73 is incubated with its substrate AMP and varying concentrations of the compound. The production of adenosine or the depletion of AMP is measured, and the IC50 is calculated.
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| Cell Assay |
The cellular activity of CD73-IN-4 is evaluated in cancer cell lines expressing CD73, such as SK-OV-3 cells. Cells are treated with CD73-IN-4, and its effect on CD73 activity is measured by quantifying adenosine production in the cell culture medium. Its effect on immune cell function can be studied in co-culture experiments.
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| Animal Protocol |
In animal studies, CD73-IN-4 would be administered to tumor-bearing mice to assess its effect on tumor growth and immune cell infiltration. Its ability to enhance the efficacy of immunotherapies, such as anti-PD-1/PD-L1 antibodies, would be evaluated.
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| ADME/Pharmacokinetics |
CD73-IN-4 is a small molecule (MW 463.81). It is soluble in DMSO. Its pharmacokinetic properties would need to be determined for specific in vivo applications.
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| Toxicity/Toxicokinetics |
Toxicology data for CD73-IN-4 is limited. As a research compound, its safety profile has not been established in formal toxicology studies. Its use is limited to research applications.
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| References | |
| Additional Infomation |
CD73-IN-4 (CAS: 2216764-29-1) is a potent and selective CD73 inhibitor that is a valuable tool for studying adenosine-mediated immunosuppression in cancer. Its high potency and selectivity make it a key compound for validating CD73 as a therapeutic target and for developing strategies to enhance anti-tumor immunity.
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| Molecular Formula |
C16H23CLN5O7P
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|---|---|
| Molecular Weight |
463.809883356094
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| Exact Mass |
463.102
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| CAS # |
2216764-29-1
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| PubChem CID |
135348940
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| Appearance |
White to off-white solid powder
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| LogP |
-0.6
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
30
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| Complexity |
641
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| Defined Atom Stereocenter Count |
4
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| SMILES |
ClC1=NC(=C2C=NN(C2=N1)[C@H]1[C@@H]([C@@H]([C@@H](COCP(=O)(O)O)O1)O)O)NC1CCCC1
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| InChi Key |
IVHVIBKVJIZKOC-RTWAVKEYSA-N
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| InChi Code |
InChI=1S/C16H23ClN5O7P/c17-16-20-13(19-8-3-1-2-4-8)9-5-18-22(14(9)21-16)15-12(24)11(23)10(29-15)6-28-7-30(25,26)27/h5,8,10-12,15,23-24H,1-4,6-7H2,(H,19,20,21)(H2,25,26,27)/t10-,11-,12-,15-/m1/s1
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| Chemical Name |
[(2R,3S,4R,5R)-5-[6-chloro-4-(cyclopentylamino)pyrazolo[3,4-d]pyrimidin-1-yl]-3,4-dihydroxyoxolan-2-yl]methoxymethylphosphonic acid
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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 : ~125 mg/mL (~269.51 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.48 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.48 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 20.8 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 | 2.1561 mL | 10.7803 mL | 21.5606 mL | |
| 5 mM | 0.4312 mL | 2.1561 mL | 4.3121 mL | |
| 10 mM | 0.2156 mL | 1.0780 mL | 2.1561 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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