| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
The target is CD73, a cell surface enzyme that is overexpressed on many cancer cells and is a key component of the adenosinergic pathway. CD73 catalyzes the dephosphorylation of AMP to adenosine, which then binds to adenosine receptors (e.g., A2AR) on immune cells. By inhibiting CD73, OP-5244 reduces the production of extracellular adenosine, thereby blocking this potent immunosuppressive signal and reactivating anti-tumor immunity.
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| ln Vitro |
In H1568 (NSCLC) cells, OP-5244 suppresses the synthesis of adenosine (ADO) with an EC50 of 0.79±0.38 nM [1]. With an EC50 of 0.22 nM, OP-5244 prevents CD8+ T lymphocytes originating from peripheral blood from hydrolyzing AMP to ADO[1]. Op-5244 (4.1-1000 nM; 96 hours) restores the proliferation and cytokine production of CD8+ T cells that are suppressed by AMP [1]. ADO synthesis in human and murine cancer cell lines (H1568 and EMT6, respectively) is totally inhibited by OP-5244 (0.01 nM-10 μM) [1].
OP-5244 potently inhibits recombinant human CD73 enzyme activity with an IC50 of 0.25 nM, indicating exceptionally high binding affinity and inhibitory efficiency. In cell-based assays using cancer cells that endogenously express CD73, the compound efficiently blocks adenosine production. Its activity translates into the reactivation of immune cells, such as T cells, that are suppressed by adenosine in the tumor microenvironment. |
| ln Vivo |
Tumor growth inhibition in mice indicates that OP-5244 (15 mg/kg/day; subcutaneously for 13 days) has anti-tumor effects when used alone [1]. In mice, OP-5244 (150 mg/kg; orally administered twice daily for 16 days) reverses immunosuppression and enhances CD8+ T cell infiltration [1]. OP-5244 (0.2 mg/kg; intravenous) has low steady-state volume of distribution (rat 0.22, dog 0.29, crab-eating monkey 0.10 L/kg/h) and moderate plasma clearance (rat 0.18, dog 1.22, macaque 0.05 L/kg/h)[1]. AUC (rat 1.96, dog 1.75, cynomolgus monkey 14.2 μM?h) and Cmax (rat 0.82, dog 1.25, cynomolgus monkey 1.72 μM) are seen with OP-5244 (10 mg/kg; oral) [1].
Specific in vivo efficacy data for OP-5244 is not detailed. However, as an orally active, potent CD73 inhibitor, its primary use is expected to be in syngeneic mouse tumor models (e.g., CT26 colon carcinoma, 4T1 breast cancer) where it would be administered orally to evaluate tumor growth inhibition and changes in the tumor immune microenvironment (e.g., increased CD8+ T cell infiltration). |
| Enzyme Assay |
For a biochemical assay, recombinant human CD73 enzyme is incubated with the substrate AMP (adenosine monophosphate) in the presence of varying concentrations of OP-5244 in an assay buffer (e.g., 25 mM MES, pH 5.5, containing 10 mM MgCl2). The reaction is allowed to proceed at 37degC. The amount of inorganic phosphate released from AMP is then quantified using a Malachite Green Phosphate Detection Kit or by measuring the product adenosine via LC-MS. The decrease in activity is used to calculate the IC50.
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| Cell Assay |
Cellular assays are performed using CD73-expressing cell lines (e.g., MDA-MB-231 breast cancer cells, WM-266-4 melanoma cells). Cells are seeded in 96-well plates and treated with OP-5244 for a set period (e.g., 30 min). The CD73 activity is then measured by adding AMP (a substrate) to the culture media, incubating at 37degC, and quantifying the amount of adenosine produced in the supernatant by LC-MS. For functional assays, CD8+ T cells are isolated and co-cultured with CD73-expressing cancer cells in the presence or absence of OP-5244, and T cell proliferation or IFN-gamma production is measured by flow cytometry or ELISA.
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| Animal Protocol |
Animal/Disease Models: balb/c (Bagg ALBino) mouse with breast cancer[1]
Doses: 15 mg/kg/day Route of Administration: Sc for 13 days Experimental Results: Inhibited tumor growth. demonstrated a 95% lower ADO/AMP ratio compared to that of the vehicle group. The in vivo efficacy of OP-5244 is assessed in a syngeneic mouse tumor model. Female Balb/c mice are injected subcutaneously with CT26 colon carcinoma cells. When tumors reach a certain size (e.g., 80-120 mm3), mice are randomized into treatment groups. OP-5244 is administered via oral gavage at a dose of 25-100 mg/kg, typically once or twice daily for 2-3 weeks. Tumor volume is measured by calipers. Upon study termination, tumors are analyzed by flow cytometry for infiltration of CD8+ T cells and by mass spectrometry for adenosine levels. |
| ADME/Pharmacokinetics |
OP-5244 is orally bioavailable and expected to have good drug-like properties. Specific quantitative PK parameters are not detailed. However, its design as a potent and selective inhibitor suggests an optimized pharmacokinetic profile to allow for oral administration and sufficient systemic exposure to reach the tumor microenvironment. It is soluble in DMSO and water for in vivo formulation.
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| Toxicity/Toxicokinetics |
Specific toxicological data for OP-5244 are not detailed. As an immune-oncology agent, the primary class-related toxicity of CD73 inhibitors is not expected to be severe, given the redundancy in the adenosine pathway. However, on-target toxicities could theoretically involve excessive immune activation or autoimmunity. These would be assessed in standard 28-day repeat-dose toxicity studies in rodents and non-rodents.
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| References | |
| Additional Infomation |
CD73 is a key checkpoint in the adenosine pathway of cancer immune evasion. OP-5244 is a research-grade chemical and a potent, selective tool for studying CD73 biology. It serves as a lead compound for developing next-generation cancer immunotherapies. As of the latest updates, it is not an approved drug and remains in the pre-clinical research phase. It is exclusively available for research purposes.
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| Molecular Formula |
C19H29CLN5O9P
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|---|---|
| Molecular Weight |
537.8884
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| Exact Mass |
535.159
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| CAS # |
2381268-71-7
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| Related CAS # |
OP-5244 sodium
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| PubChem CID |
154585769
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| Appearance |
White to pink solid powder
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| LogP |
-1.6
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| Hydrogen Bond Donor Count |
6
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| Hydrogen Bond Acceptor Count |
13
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
35
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| Complexity |
764
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| Defined Atom Stereocenter Count |
5
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| SMILES |
ClC1=NC(=C2C([H])=NN(C2=N1)[C@@]1([H])[C@@]([H])([C@@]([H])([C@@]([H])(C([H])([H])O[C@@](C([H])([H])O[H])(C([H])([H])OC([H])([H])[H])P(=O)(O[H])O[H])O1)O[H])O[H])N([H])C1([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H]
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| InChi Key |
MVKIUWCYHMQOCI-VVZOVNLRSA-N
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| InChi Code |
InChI=1S/C20H31ClN5O8P/c1-33-10-20(9-27,35(30,31)32)7-6-13-14(28)15(29)18(34-13)26-17-12(8-22-26)16(24-19(21)25-17)23-11-4-2-3-5-11/h8,11,13-15,18,27-29H,2-7,9-10H2,1H3,(H,23,24,25)(H2,30,31,32)/t13-,14-,15-,18-,20-/m1/s1
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| Chemical Name |
((R)-4-((2R,3S,4R,5R)-5-(6-chloro-4-(cyclopentylamino)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3,4-dihydroxytetrahydrofuran-2-yl)-1-hydroxy-2-(methoxymethyl)butan-2-yl)phosphonic acid
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| Synonyms |
OP5244 OP 5244 OP-5244
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 : ~250 mg/mL (~464.78 mM)
H2O : ~100 mg/mL (~185.91 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 6.5 mg/mL (12.08 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 65.0 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: ≥ 6.5 mg/mL (12.08 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 65.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 6.5 mg/mL (12.08 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8591 mL | 9.2956 mL | 18.5912 mL | |
| 5 mM | 0.3718 mL | 1.8591 mL | 3.7182 mL | |
| 10 mM | 0.1859 mL | 0.9296 mL | 1.8591 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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