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| Targets |
ERCC1-XPF-IN-2 targets the ERCC1-XPF endonuclease complex, a structure-specific endonuclease that plays a key role in nucleotide excision repair (NER) and interstrand crosslink repair. The ERCC1-XPF complex incises DNA on the 5' side of a lesion during NER, a process that removes UV-induced DNA damage and other bulky adducts. By inhibiting this endonuclease with an IC50 of 0.6 μM, the compound blocks the repair of DNA damage, thereby sensitizing cells to DNA-damaging agents such as cisplatin. This mechanism makes it a valuable tool for studying DNA repair pathways and for potential use in combination with chemotherapy.
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| ln Vitro |
ERCC1-XPF-IN-2 (compound 13) (0-100 µM) has DNase I and FEN-1 activity with IC50 values >100 and >100 µM, respectively [1]. The binding kinetics of ERCC1-XPF-IN-2 are sluggish, with a Kd value of about 30 µM [1]. Hep-G2 cells are not affected by ERCC1-XPF-IN-2 at concentrations up to 10 µM. Mice and humans have relatively short half-lives (t1/2 values of 23 minutes and 28 minutes, respectively) for their microsomes. Nucleotide excision repair (NER) in A375 cells is inhibited by ERCC1-XPF-IN-2 (0-60 µM; 24 h) with an IC50 value of 15.6 µM [1]. Without causing toxicity, ERCC1-XPF-IN-2 (0-60 µM) boosts cisplatin action [1]. Delays in DNA repair are caused by ERCC1-XPF-IN-2 (10 µM; 6h), which right-shifts more γH2AX foci per cell [1].
In vitro, ERCC1-XPF-IN-2 is a potent inhibitor of the ERCC1-XPF endonuclease with an IC50 of 0.6 μM. The compound shows activity in nucleotide excision repair assays, indicating its ability to block the repair of UV-induced DNA damage. It enhances the cytotoxicity of cisplatin in cell-based assays. The compound has a slow binding kinetics with a Kd of approximately 30 μM. It shows no significant inhibition of FEN-1 and DNase I (IC50 >100 μM). In human A375 cells, it has an IC50 of 15.6 μM for reducing NER of UV-damaged plasmids. The compound is not toxic to Hep-G2 cells at 10 μM. |
| ln Vivo |
In vivo data for ERCC1-XPF-IN-2 are limited. The compound is a research tool used primarily for in vitro and preclinical studies. It has been reported that the compound has relatively short half-lives in mouse and human microsomes, with t1/2 values of 23 minutes and 13 minutes, respectively. This suggests rapid metabolic clearance, which may limit its in vivo efficacy. The compound is being investigated for its potential to sensitize cancer cells to DNA-damaging therapies, but specific in vivo efficacy data are not available.
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| Enzyme Assay |
In vitro enzyme assays for ERCC1-XPF-IN-2 involve measuring the inhibition of the ERCC1-XPF endonuclease activity. The enzyme complex is incubated with a DNA substrate containing a lesion and varying concentrations of the compound. The cleavage of the DNA substrate is measured, and the IC50 value (0.6 μM) is determined. Binding kinetics are assessed using surface plasmon resonance (SPR) or similar techniques to determine the Kd (approximately 30 μM). Selectivity is assessed by testing the compound against other nucleases such as FEN-1 and DNase I.
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| Cell Assay |
Cytotoxicity Assay[1]
Cell Types: A375 Cell Tested Concentrations: 0-60 µM Incubation Duration: Experimental Results: Did not show any toxicity and increased cisplatin activity to 1.5 times (PF50). In vitro cell-based assays for ERCC1-XPF-IN-2 are conducted in cancer cell lines such as A375 (melanoma) and Hep-G2 (hepatoma). Cells are treated with the compound at various concentrations, and DNA repair capacity is assessed using a GFP reporter assay for nucleotide excision repair. The compound's ability to enhance cisplatin cytotoxicity is evaluated by co-treating cells with the compound and cisplatin and measuring cell viability. γH2AX assays are used to assess DNA double-strand breaks as a marker of DNA damage. |
| Animal Protocol |
In vivo animal experiments with ERCC1-XPF-IN-2 are not extensively documented. Based on its mechanism, typical study designs would involve administration of the compound in xenograft models in combination with DNA-damaging agents such as cisplatin. However, the compound's short half-life in microsomes (t1/2 = 23 minutes in mouse, 13 minutes in human) may limit its in vivo application. Dosing regimens and routes of administration would need to be optimized. The compound is for research use only.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of ERCC1-XPF-IN-2 are limited. The compound has a molecular formula of C15H13Cl2NO3 and a molecular weight of 326.17. It has been reported to have relatively short half-lives in mouse and human microsomes, with t1/2 values of 23 minutes and 13 minutes, respectively. This suggests rapid metabolic clearance. The compound is soluble in DMSO. Storage: powder at -20°C for 3 years; in solvent at -80°C for 1 year. Specific data on bioavailability, volume of distribution, and protein binding are not available.
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| Toxicity/Toxicokinetics |
Safety and toxicology data for ERCC1-XPF-IN-2 are limited. The compound is for research use only and is not approved for human therapeutic use. In cell-based assays, it showed no toxicity to Hep-G2 cells at 10 μM. Standard laboratory safety precautions should be followed when handling the compound. The compound should be stored properly and disposed of in accordance with applicable regulations. No specific LD50 or organ toxicity data are available.
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| References | |
| Additional Infomation |
ERCC1-XPF-IN-2 has CAS number 1808986-37-9, molecular formula C15H13Cl2NO3, and molecular weight 326.17. It is a potent ERCC1-XPF endonuclease inhibitor with an IC50 of 0.6 μM. It shows activity in nucleotide excision repair, cisplatin enhancement, and γH2AX assays. It has slow binding kinetics with a Kd of approximately 30 μM. It is a research tool for studying DNA repair and sensitizing cancer cells to DNA-damaging therapies. Purity: typically ≥98%. Not for human use; for research purposes only.
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| Molecular Formula |
C15H13CL2NO3
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| Molecular Weight |
326.174622297287
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| Exact Mass |
325.027
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| CAS # |
1808986-37-9
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| PubChem CID |
122189958
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| Appearance |
White to off-white solid powder
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| LogP |
3.2
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
21
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| Complexity |
356
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C(C1C=CC(Cl)=CC=1Cl)C(=O)NCC1C=CC(O)=C(O)C=1
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| InChi Key |
BKPCQXGBKRAJDW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H13Cl2NO3/c16-11-3-2-10(12(17)7-11)6-15(21)18-8-9-1-4-13(19)14(20)5-9/h1-5,7,19-20H,6,8H2,(H,18,21)
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| Chemical Name |
2-(2,4-dichlorophenyl)-N-[(3,4-dihydroxyphenyl)methyl]acetamide
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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: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 (~766.47 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 | 3.0659 mL | 15.3294 mL | 30.6589 mL | |
| 5 mM | 0.6132 mL | 3.0659 mL | 6.1318 mL | |
| 10 mM | 0.3066 mL | 1.5329 mL | 3.0659 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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