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Purity: =99.15%
| Targets |
UNC-10217938A targets the endosomal membrane, destabilizing it to facilitate the escape of macromolecules from endosomes into the cytosol. The compound enhances the endosome-leakage activity of cell-penetrating peptides and promotes the endosomal escape of macromolecules such as oligonucleotides. Its mechanism involves disruption of the endosomal membrane, allowing trapped molecules to escape into the cytosol and reach their intracellular targets. This makes it a valuable tool for improving the delivery of therapeutic oligonucleotides and other macromolecules.
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| ln Vitro |
Compared to Retro-1, UNC10217938A is significantly more effective and potent as it significantly increases luciferase induction in HelaLuc705 cells within the 5-25 µM range. UNC10217938A offers a 60-fold enhancement at 10 µM and a 220-fold enhancement at 20 µM when compared to splice switching oligonucleotide (SSO) alone[1]. In contrast, 100 µM Retro-1 only delivers an 11-fold enhancement. Receptor-targeted oligonucleotide conjugates can have their effects significantly increased by UNC10217938A. UNC10217938A has the ability to amplify the effects of both negatively charged and uncharged morpholino oligonucleotides[1]. Cells exposed to UNC10217938A exhibit a significant decrease in TAMRA-oligonucleotide co-localization with the late endosome marker Rab7, but little change in co-localization with the lysosomal marker LAMP-1. UNC10217938A induces a partial release of oligonucleotides into the cytosol from late endosomes through nuclear accumulation[1].
UNC-10217938A exhibits potent in vitro activity as an endosomal escape enhancer. It causes partial release of oligonucleotides from late endosomes to the cytosol, followed by nuclear accumulation. The compound substantially enhances the effects of receptor-targeted oligonucleotide conjugates. Its activity is assessed in cell-based assays measuring the intracellular distribution and functional activity of oligonucleotides. These in vitro activities confirm its utility as a tool for improving macromolecule delivery. |
| ln Vivo |
In EGFP654 mice, systemic treatment with SSO623 and intravenous injection of UNC10217938A (7.5 mg/kg) result in discernible increases in EGFP fluorescence in the liver, kidney, and heart[3].
In vivo activity of UNC-10217938A has been demonstrated in animal models. The compound has been shown to reduce the growth of cancer cells in vitro and to inhibit tumor formation in mice. As an endosomal escape enhancer, it can improve the delivery and efficacy of therapeutic oligonucleotides in vivo. However, detailed in vivo data are limited, as the compound is primarily used as a research tool. Further studies are needed to fully characterize its therapeutic potential. |
| Enzyme Assay |
In vitro assays for UNC-10217938A involve measuring its ability to enhance endosomal escape of macromolecules. Cells are treated with the compound and a fluorescently labeled oligonucleotide or macromolecule. The intracellular distribution of the macromolecule is assessed by confocal microscopy or flow cytometry. The functional activity of the delivered macromolecule (e.g., gene silencing by siRNA) is measured. These assays confirm the compound's activity as an endosomal escape enhancer.
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| Cell Assay |
In vitro cellular assays for UNC-10217938A are conducted in mammalian cell lines. Cells are treated with the compound at various concentrations, and cell viability is assessed to determine cytotoxicity. The compound's effects on oligonucleotide delivery and function are assessed by measuring the intracellular distribution and activity of the oligonucleotide. These assays characterize the compound's utility for improving macromolecule delivery.
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| Animal Protocol |
In vivo animal experiments with UNC-10217938A are conducted in mouse models of cancer or other diseases where oligonucleotide therapeutics are being evaluated. The compound is administered along with the therapeutic oligonucleotide. Tumor growth, gene silencing, and other therapeutic endpoints are assessed. These studies evaluate the compound's ability to enhance the delivery and efficacy of oligonucleotide therapeutics in vivo.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for UNC-10217938A are limited. The compound has a molecular weight of 456.54 and is soluble in DMSO. Its bioavailability and half-life have not been extensively characterized. The compound is typically stored at -20°C. Further PK studies would be needed to support any potential clinical development.
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| Toxicity/Toxicokinetics |
UNC-10217938A is considered to have low toxicity based on its use as a research compound. However, comprehensive toxicological evaluations have not been extensively published. The compound is intended for research use only and is not approved for human therapeutic use. Standard laboratory safety precautions should be followed when handling this compound.
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| References | |
| Additional Infomation |
UNC-10217938A (UNC7938) is a 3-deazapteridine analog with high oligonucleotide enhancing effects. It is a destabilizer of the endosome membrane that can enhance the endosome-leakage activity of cell-penetrating peptides and facilitate the endosomal escape of macromolecules. The compound causes partial release of oligonucleotides from late endosomes to the cytosol followed by nuclear accumulation. It is available in high purity (≥99%) for research applications. Its ability to enhance macromolecule delivery makes it a valuable tool for oligonucleotide therapeutics research.
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| Molecular Formula |
C26H28N6O2
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|---|---|
| Molecular Weight |
456.5395
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| Exact Mass |
456.227
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| CAS # |
1347749-97-6
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| PubChem CID |
57402790
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
4.1
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
34
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| Complexity |
622
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O(C([H])([H])C([H])([H])[H])C(N([H])C1C([H])=C(C2=C(N=1)N=C(C1C([H])=C([H])C([H])=C([H])C=1[H])C(C1C([H])=C([H])C([H])=C([H])C=1[H])=N2)N([H])C([H])([H])C([H])([H])N(C([H])([H])[H])C([H])([H])[H])=O
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| InChi Key |
HHICWLZMNOCMIQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H28N6O2/c1-4-34-26(33)29-21-17-20(27-15-16-32(2)3)24-25(28-21)31-23(19-13-9-6-10-14-19)22(30-24)18-11-7-5-8-12-18/h5-14,17H,4,15-16H2,1-3H3,(H2,27,28,29,31,33)
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| Chemical Name |
ethyl N-[8-[2-(dimethylamino)ethylamino]-2,3-diphenylpyrido[2,3-b]pyrazin-6-yl]carbamate
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| Synonyms |
UNC 7938UNC 10217938A UNC7938 UNC 10217938A UNC-7938UNC10217938AUNC-10217938-A
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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 : ~10 mg/mL (~21.90 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1 mg/mL (2.19 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 + to the above solution and mix evenly; then add 450 μL of 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1904 mL | 10.9519 mL | 21.9039 mL | |
| 5 mM | 0.4381 mL | 2.1904 mL | 4.3808 mL | |
| 10 mM | 0.2190 mL | 1.0952 mL | 2.1904 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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