| Size | Price | Stock | Qty |
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| 5mg |
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| 50mg |
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| Targets |
DNA relaxation-IN-1 targets DNA Ligase 1 (Lig1), a member of the ATP-dependent DNA ligase family that plays a critical role in DNA replication and repair. Lig1 is responsible for sealing Okazaki fragments during DNA replication and for joining DNA breaks during base excision repair and nucleotide excision repair. By inhibiting Lig1, DNA relaxation-IN-1 disrupts DNA ligation and the DNA relaxation activity of Lig1. This inhibition leads to the accumulation of DNA breaks and promotes apoptosis in targeted cells. The compound's selectivity for Lig1 makes it a valuable tool for studying the specific role of this enzyme in DNA repair and replication, and for exploring its potential as a therapeutic target in cancer.
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| ln Vitro |
In vitro, DNA relaxation-IN-1 is a selective inhibitor of DNA Ligase 1 (Lig1). It inhibits DNA ligation and disrupts Lig1's DNA relaxation activity. The compound's activity can be measured in biochemical assays using recombinant Lig1 and DNA substrates. When combined with Topotecan, a topoisomerase inhibitor, DNA relaxation-IN-1 exhibits synergistic antiproliferative effects against colorectal cancer cells. This synergy suggests that combining Lig1 inhibition with topoisomerase inhibition may be an effective strategy for cancer therapy. The compound's ability to promote apoptosis in targeted cells further supports its potential as an anticancer agent. Specific IC50 values for Lig1 inhibition have not been extensively reported.
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| ln Vivo |
In vivo activity data for DNA relaxation-IN-1 are not available in the current scientific literature. As a DNA Ligase 1 inhibitor with demonstrated synergistic antiproliferative effects in vitro, the compound would be expected to have antitumor activity in vivo, particularly in combination with Topotecan. However, specific animal model studies, dosing regimens, and quantitative outcomes have not been reported. The compound's selectivity for Lig1 and its ability to promote apoptosis suggest that it may have potential for in vivo applications. Further in vivo studies would be required to characterize its efficacy, safety, and pharmacokinetic properties in animal models of cancer.
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| Enzyme Assay |
In vitro enzyme assay protocols for DNA relaxation-IN-1 typically involve measuring its inhibition of DNA Ligase 1 (Lig1) activity. A standard protocol would involve incubating recombinant human Lig1 with varying concentrations of DNA relaxation-IN-1 (typically 0.1 nM to 10 μM), a DNA substrate (e.g., a nicked or gapped DNA duplex), and ATP in assay buffer (e.g., Tris-HCl, pH 7.5, with MgCl2, DTT, and BSA) at 37°C for a defined period (e.g., 30-60 minutes). The extent of DNA ligation is measured by gel electrophoresis, fluorescence-based assays, or scintillation counting using radiolabeled DNA. IC50 values are determined from concentration-response curves. DNA relaxation activity can be assessed using supercoiled DNA substrates and monitoring the conversion to relaxed forms by gel electrophoresis.
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| Cell Assay |
In vitro cell-based assay protocols for DNA relaxation-IN-1 typically involve assessing its effects on cell proliferation, DNA repair, and apoptosis in cancer cell lines. A standard protocol would involve seeding colorectal cancer cells or other cancer cell lines in multi-well plates and treating them with varying concentrations of DNA relaxation-IN-1 (typically 0.1 nM to 10 μM) alone or in combination with Topotecan. Cell proliferation is measured using MTT, CCK-8, or colony formation assays. Apoptosis is assessed by Annexin V staining, caspase activity assays, or DNA fragmentation analysis. DNA damage and repair can be assessed by measuring γ-H2AX foci formation or by comet assays. Appropriate controls include vehicle-treated cells and cells treated with Topotecan alone.
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| Animal Protocol |
In vivo animal experimental protocols for DNA relaxation-IN-1 have not been reported in the available literature. Based on its in vitro synergy with Topotecan against colorectal cancer cells, potential studies might involve using mouse xenograft models of colorectal cancer. A hypothetical protocol would involve implanting colorectal cancer cells subcutaneously in immunodeficient mice, allowing tumors to reach a certain size, and then administering DNA relaxation-IN-1 alone or in combination with Topotecan. The compound can be formulated using standard vehicles such as DMSO:PEG300:Tween 80:Saline. Treatment would typically be administered daily or every other day for 2-4 weeks. Endpoints would include tumor volume measurement, tumor weight at necropsy, assessment of apoptosis and DNA damage in tumor tissues, and evaluation of combination effects.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of DNA relaxation-IN-1 have not been characterized in published studies. The compound has a molecular weight of 493.62 and a molecular formula of C30H27N3O2S. It is soluble in DMSO at 100 mg/mL (202.58 mM). The compound should be stored at -20°C. Specific PK parameters such as half-life, Cmax, AUC, bioavailability, volume of distribution, and clearance have not been reported. The compound's metabolism, protein binding, and routes of elimination remain to be characterized. Further pharmacokinetic studies would be required to understand its absorption, distribution, metabolism, and excretion profile.
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| Toxicity/Toxicokinetics |
Toxicological data for DNA relaxation-IN-1 are limited, as the compound is intended for research use only and has not undergone systematic toxicity testing. No acute toxicity (LD50), subchronic toxicity, genotoxicity, or reproductive toxicity studies have been reported specifically for this compound. As a DNA Ligase 1 inhibitor, potential on-target toxicities could include effects on DNA replication and repair in normal cells, which may lead to genotoxicity or myelosuppression. However, these have not been evaluated specifically for DNA relaxation-IN-1. The compound is not intended for human use. Researchers should follow standard safety precautions when handling the compound, including working in a fume hood, wearing appropriate personal protective equipment, and avoiding inhalation, ingestion, or skin contact.
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| References | |
| Additional Infomation |
DNA relaxation-IN-1 is a research-grade compound that functions as a selective inhibitor of DNA Ligase 1 (Lig1). It inhibits DNA ligation and disrupts Lig1's DNA relaxation activity. When combined with Topotecan, DNA relaxation-IN-1 exhibits synergistic antiproliferative effects against colorectal cancer cells. The compound promotes apoptosis in targeted cells and is used in research on DNA repair mechanisms and cancer therapeutics. It has not entered clinical trials and is not approved for any therapeutic indication. Its mechanism of action involves inhibition of DNA Ligase 1, leading to the accumulation of DNA breaks and cell death. The compound is available exclusively for research purposes and is not intended for diagnostic, therapeutic, or human applications.
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| Molecular Formula |
C30H27N3O2S
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| Molecular Weight |
493.62
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| Exact Mass |
493.182
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| CAS # |
2190506-29-5
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| PubChem CID |
145957134
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| Appearance |
Typically exists as solid at room temperature
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| Hydrogen Bond Donor Count |
2
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
36
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| Complexity |
959
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=C(C2=CC=CC=C2N1)C3C4=C(C(=CC(=C4)/C=C/C(=O)C5=CC=CS5)C(C)(C)C)OC(=C3C#N)N
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| InChi Key |
XAAIDHPZKXBLMF-VAWYXSNFSA-N
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| InChi Code |
InChI=1S/C30H27N3O2S/c1-17-26(19-8-5-6-9-23(19)33-17)27-20-14-18(11-12-24(34)25-10-7-13-36-25)15-22(30(2,3)4)28(20)35-29(32)21(27)16-31/h5-15,27,33H,32H2,1-4H3/b12-11+
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| Chemical Name |
2-amino-8-tert-butyl-4-(2-methyl-1H-indol-3-yl)-6-[(E)-3-oxo-3-thiophen-2-ylprop-1-enyl]-4H-chromene-3-carbonitrile
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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) |
Typically soluble in DMSO (e.g. 10 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0258 mL | 10.1292 mL | 20.2585 mL | |
| 5 mM | 0.4052 mL | 2.0258 mL | 4.0517 mL | |
| 10 mM | 0.2026 mL | 1.0129 mL | 2.0258 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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