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| Targets |
NUC-7738 is a 5′-aryloxy phosphoramidate prodrug of 3′-deoxyadenosine (3′-dA). Upon cellular uptake, it is metabolized to the active nucleotide, which inhibits key enzymes involved in DNA replication and repair, disrupting the growth and survival of cancer cells. It targets hematological cancer cells.
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| ln Vitro |
NUC-7738 (compound 7a) exhibited cytotoxic and anticancer effects on leukocyte lineage cells with an LC50 value of less than 30 μM. It was tested against CCRF-CEM, HL-60, KG-1, MOLT-4, K562, MV4-11, THP-1, HEL92, NCI-H929, RPMI-8226, Jurkat, Z138, RL, HS445, HepG2, MCF-7, Bx-PC-3, HT29, MIA PaCa-2, and SW620 cells. NUC-7738 (1 μM) exhibits a t1/2 value of 48.1 min, indicating high stability in human hepatocytes[1]. With no change in plasma concentration for up to 4 hours, NUC-7738 is more stable in human plasma than the parent nucleoside [1].
In vitro, NUC-7738 has potent cytotoxic activity against a panel of hematological cancer cell lines. It exhibited cytotoxic and anticancer effects on leukocyte lineage cells with an LC50 value of less than 30 µM. It is more stable in human plasma compared to the parent nucleoside, with plasma concentrations unchanged for up to 4 hours. |
| ln Vivo |
NUC-7738 has demonstrated cytotoxic activity in preclinical cancer models. As a ProTide prodrug, it is designed to selectively accumulate in tumor cells, enhancing its therapeutic efficacy while minimizing damage to normal tissues. It can be used in cancer research.
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| Enzyme Assay |
In vitro assays for NUC-7738 typically involve cell viability assays. A standard protocol involves culturing hematological cancer cell lines in 96-well plates and treating them with varying concentrations of NUC-7738 (typically 0.1-100 µM) for 48-72 hours. Cell viability is assessed using MTT or CellTiter-Glo assays. LC50 values are calculated from dose-response curves.
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| Cell Assay |
In vitro cell culture experiments with NUC-7738 typically involve hematological cancer cell lines. Cells are cultured in appropriate media and treated with the compound at concentrations ranging from 0.1-100 µM for 48-72 hours. Cell viability, apoptosis, and cell cycle are measured.
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| Animal Protocol |
In vivo animal studies with NUC-7738 are conducted in xenograft models of hematological malignancies. A typical protocol involves administering the compound intravenously or orally to tumor-bearing mice at doses ranging from 1-50 mg/kg. Tumor volume and survival are monitored.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of NUC-7738 are characterized by its stability in human plasma, where it remains unchanged for up to 4 hours. As a ProTide prodrug, it is designed to improve cellular delivery.
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| Toxicity/Toxicokinetics |
NUC-7738 is a research compound and has not been evaluated for toxicity in humans. Standard laboratory safety precautions should be followed when handling this compound, including the use of gloves and safety glasses.
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| References |
[1]. Serpi M, et, al. Synthesis and Characterization of NUC-7738, an Aryloxy Phosphoramidate of 3'-Deoxyadenosine, as a Potential Anticancer Agent. J Med Chem. 2022 Dec 8;65(23):15789-15804.
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| Additional Infomation |
Fosdesdenosine Sipalabenamide is a phosphoramide derivative of cordycepin (3'-deoxyadenosine; 3'-dA) monophosphate. Cordycepin is an adenosine derivative, originally isolated from Cordyceps sinensis, and possesses potential antitumor, antioxidant, and anti-inflammatory activities. After passive diffusion into cells, Fosdesdenosine Sipalabenamide converts cordycepin monophosphate (3'-dAMP) into its active anticancer metabolite, 3'-deoxyadenosine triphosphate (3'-dATP). 3'-dATP, as a ribonucleoside analog, competes with ATP during transcription. Therefore, this drug inhibits RNA synthesis, suppresses cell proliferation, and induces apoptosis. Furthermore, 3'-dAMP activates AMP-activated protein kinase (AMPK) and reduces the activity of the mammalian target of rapamycin (mTOR) signaling pathway. This prevents the hyperphosphorylation of the translation repressor protein 4E-BP1, thereby inducing tumor cell apoptosis and inhibiting tumor cell proliferation. mTOR is a serine/threonine kinase belonging to the phosphatidylinositol 3-kinase (PI3K)-associated kinase (PIKK) family. It plays a crucial role in the PI3K/AKT/mTOR signaling pathway, which regulates cell growth and proliferation, and its expression or activity is frequently aberrant in human cancers. Compared to cordycepin alone, the addition of a phosphoramide group may overcome cancer resistance and enhance cytotoxicity because noradrenaline phosphate cipalafenamide does not require nucleoside transporters for cellular uptake, is independent of enzymatic activation by adenosine kinase (AK), and is not easily degraded by adenosine deaminase (ADA). In conclusion, this may contribute to overcoming cancer resistance to cordycepin.
NUC-7738 is a ProTide nucleoside analogue prodrug of 3′-deoxyadenosine with potent cytotoxic activity against hematological cancer cell lines. It can be used in cancer research. It has not undergone clinical trials and is not approved as a pharmaceutical. |
| Molecular Formula |
C26H29N6O7P
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|---|---|
| Molecular Weight |
568.518226385117
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| Exact Mass |
568.183
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| CAS # |
2348493-39-8
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| PubChem CID |
166177279
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| Appearance |
White to off-white solid powder
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| LogP |
1.8
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
12
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
40
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| Complexity |
877
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| Defined Atom Stereocenter Count |
4
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| SMILES |
C[C@@H](C(=O)OCC1=CC=CC=C1)NP(=O)(OC[C@@H]2C[C@H]([C@@H](O2)N3C=NC4=C(N=CN=C43)N)O)OC5=CC=CC=C5
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| InChi Key |
UDLWWGQHMQIYCV-LKKHFEEPSA-N
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| InChi Code |
InChI=1S/C26H29N6O7P/c1-17(26(34)36-13-18-8-4-2-5-9-18)31-40(35,39-19-10-6-3-7-11-19)37-14-20-12-21(33)25(38-20)32-16-30-22-23(27)28-15-29-24(22)32/h2-11,15-17,20-21,25,33H,12-14H2,1H3,(H,31,35)(H2,27,28,29)/t17-,20-,21+,25+,40?/m0/s1
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| Chemical Name |
benzyl (2S)-2-[[[(2S,4R,5R)-5-(6-aminopurin-9-yl)-4-hydroxyoxolan-2-yl]methoxy-phenoxyphosphoryl]amino]propanoate
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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: 100 mg/mL (175.90 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.40 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 25.0 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: ≥ 2.5 mg/mL (4.40 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 25.0 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 | 1.7590 mL | 8.7948 mL | 17.5895 mL | |
| 5 mM | 0.3518 mL | 1.7590 mL | 3.5179 mL | |
| 10 mM | 0.1759 mL | 0.8795 mL | 1.7590 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.
Link: https://clinicaltrials.gov/ct2/show/NCT03829254
Conditions:Advanced Cancer|Lymphoma|Solid Tumor|MelanomaProducts are for research use only; We do not sell to patients
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