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| Targets |
Homologous recombination-IN-1 targets the protein-protein interaction between RAD51 and BRCA2, two key proteins involved in homologous recombination DNA repair. RAD51 is a recombinase that facilitates strand invasion and exchange during HR, while BRCA2 serves as a mediator that loads RAD51 onto single-stranded DNA. By inhibiting the RAD51-BRCA2 interaction, the compound prevents the formation of RAD51 filaments and disrupts HR repair. This makes HR-deficient cells, such as those with BRCA1 or BRCA2 mutations, particularly sensitive to the compound's effects through synthetic lethality.
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| ln Vitro |
In a dose-dependent manner, homologous recombination-IN-1 (10–40 μM; 5 h) decreases homologous recombination in cells[1].
In vitro studies demonstrate that Homologous recombination-IN-1 is a potent inhibitor of the RAD51-BRCA2 interaction with an EC₅0 of 19 microM. The compound reduces homologous recombination in cells in a dose-dependent manner at concentrations of 10-40 microM. Its in vitro activity is assessed using cell-based recombination assays, such as the DR-GFP reporter system, which measures HR efficiency. The compound's ability to inhibit RAD51-BRCA2 binding may be confirmed using co-immunoprecipitation or proximity ligation assays in treated cells. Its effects on cell viability are assessed in cancer cell lines with varying HR proficiency. |
| ln Vivo |
In vivo activity of Homologous recombination-IN-1 has not been extensively characterized in the literature. As a small molecule inhibitor of RAD51-BRCA2 interaction, the compound has potential applications in cancer therapy, particularly for tumors with HR deficiencies. The compound's in vivo efficacy would depend on its ability to reach target tissues and inhibit the RAD51-BRCA2 interaction. However, detailed in vivo efficacy data, including tumor growth inhibition in xenograft models, are not reported in the available literature. The compound is primarily used as a research tool for in vitro studies of HR repair.
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| Enzyme Assay |
In vitro enzyme/receptor binding assays for Homologous recombination-IN-1 focus on measuring its ability to disrupt the RAD51-BRCA2 protein-protein interaction. The assay typically uses purified recombinant RAD51 and BRCA2 proteins or peptides representing the interaction interface. Binding is assessed using surface plasmon resonance (SPR), isothermal titration calorimetry (ITC), or fluorescence polarization with labeled proteins. The compound is incubated with the proteins at varying concentrations, and the degree of interaction inhibition is quantified. EC₅0 values are calculated from dose-response curves. Alternatively, ELISA-based assays using immobilized RAD51 and biotinylated BRCA2 can be used to measure the inhibitory activity.
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: BxPC3 cells Tested Concentrations: 10-40 μM Incubation Duration: 5 hrs (hours) Experimental Results: Led to homologous recombination inhibition with an EC50 value of 18.4 μM. Cellular assays for Homologous recombination-IN-1 are conducted using cell lines to assess its inhibition of homologous recombination. The DR-GFP reporter assay is commonly used, where cells contain a genomic GFP reporter that is activated only upon successful HR repair. Cells are treated with the compound (10-40 microM) for 5 hours, and HR efficiency is measured by flow cytometry as the percentage of GFP-positive cells. The compound's effects on cell viability and proliferation are assessed using MTT or colony formation assays. RAD51 focus formation is evaluated by immunofluorescence microscopy to confirm disruption of RAD51 function. |
| Animal Protocol |
In vivo animal studies for Homologous recombination-IN-1 are limited, as the compound is primarily used as a research tool. For in vivo efficacy studies, xenograft models using HR-deficient cancer cell lines could be employed. Tumor-bearing mice would be treated with the compound via intraperitoneal or oral administration at various doses. Tumor volume would be measured regularly, and body weight monitored for tolerability. At study termination, tumors would be analyzed for HR repair efficiency, RAD51 focus formation, and apoptosis markers. However, specific in vivo study protocols and results are not extensively reported in the available literature.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of Homologous recombination-IN-1 have not been extensively characterized in the literature. The compound has a molecular weight of 485.96 g/mol and a molecular formula of C2₈H24ClN3O3. It is a small molecule inhibitor that may have reasonable oral bioavailability, though this has not been confirmed. The compound is available in high purity (≥98%). Detailed PK parameters such as half-life, volume of distribution, and bioavailability are not reported. The compound's physicochemical properties suggest it could be formulated for in vivo administration using standard approaches, though specific formulation data are not available.
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| Toxicity/Toxicokinetics |
Toxicological data for Homologous recombination-IN-1 are limited, as the compound is used primarily as a research tool rather than a therapeutic agent. The compound is not intended for human therapeutic use and is supplied for research purposes only. In cell-based assays, the compound is generally well-tolerated at concentrations used for HR inhibition (10-40 microM). Higher concentrations may cause non-specific effects or cytotoxicity. Standard safety precautions should be followed when handling this compound. Specific toxicity profiles in animal models are not reported in the available literature.
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| References | |
| Additional Infomation |
Homologous recombination-IN-1 is a potent inhibitor of the RAD51-BRCA2 protein-protein interaction with an EC₅0 of 19 microM. It obstructs homologous recombination by preventing RAD51 loading onto DNA, making it a valuable tool for studying DNA repair mechanisms and synthetic lethality in cancer research. The compound has potential applications in cancer therapy, particularly for tumors with HR deficiencies. It is a small molecule inhibitor that can interfere with homologous recombination in a dose-dependent manner. The compound is not an FDA-approved drug and has no clinical indications. It is available in high purity and is typically stored at -20degC.
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| Molecular Formula |
C28H24CLN3O3
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| Molecular Weight |
485.96
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| Exact Mass |
485.15
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| Elemental Analysis |
C, 69.20; H, 4.98; Cl, 7.29; N, 8.65; O, 9.88
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| CAS # |
391889-85-3
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| PubChem CID |
4246127
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Index of Refraction |
1.660
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| LogP |
4.39
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
35
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| Complexity |
873
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1C=CC2=C(C=1)C(C1C=CC=CC=1)=C(C(N2)=O)C1CC(C2C=CC(=CC=2)OC)N(C(CC)=O)N=1
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| InChi Key |
LAVOKBSCOSIGER-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C28H24ClN3O3/c1-3-25(33)32-24(17-9-12-20(35-2)13-10-17)16-23(31-32)27-26(18-7-5-4-6-8-18)21-15-19(29)11-14-22(21)30-28(27)34/h4-15,24H,3,16H2,1-2H3,(H,30,34)
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| Chemical Name |
6-chloro-3-[3-(4-methoxyphenyl)-2-propanoyl-3,4-dihydropyrazol-5-yl]-4-phenyl-1H-quinolin-2-one
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| Synonyms |
CAY10760
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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 : ~50 mg/mL (~102.9 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 | 2.0578 mL | 10.2889 mL | 20.5778 mL | |
| 5 mM | 0.4116 mL | 2.0578 mL | 4.1156 mL | |
| 10 mM | 0.2058 mL | 1.0289 mL | 2.0578 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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