LC-1-40
Based on 1 Customer Validation
LC-1-40 is a selective NUDT1 PROTAC degrader with a DC50 of 0.97 nM. LC-1-40 recruits NUDT1 to the CRBN E3 ubiquitin ligase complex, achieving degradation through a proteasome-dependent pathway. LC-1-40 leads to increased intratumoral nucleotide damage and cell Apoptosis. LC-1-40 can be used for research related to Mycn-amplified neuroblastoma.
(Pink: MTH1/NUDT1 ligand (HY-187054); Blue: Cereblon ligand (HY-W023573); Black: linker).
Para uso exclusivo en investigación. No vendemos a pacientes.
- Pureza : 99.65%
- Fòrmula: C49H48N8O6
- Peso molecular:844.96
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Almacenamiento:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Actividad biológica
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Chemical Information
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Solvente y solubilidad
- Protocolo
- Pureza y Documentación
- Referencias
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Help & FAQs
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Actividad biológica
Descripciòn
IC50 & Target
[1]|
Cereblon |
In Vitro
LC-1-40 (50 nM; 6 h) degrades NUDT1 in SF188 cells via a CRBN- and proteasome-dependent PROTAC mechanism[1].
LC-1-40 (100 nM; 6 h) selectively degrades NUDT1 in SF188 cells with minimal off-target effects on the global proteome[1].
LC-1-40 (50 nM; 36 h) exerts cytotoxic activity in SHEP MYCN-ER cells that is strictly dependent on targeted degradation of NUDT1, as the degradation-resistant E77K mutant completely rescues cell death[1].
LC-1-40 reduces NUDT1 protein levels in Kelly and SF188 cells but does not affect NUDT1 mRNA expression[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:SF188 human glioblastoma cells
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Concentration:50 nM (LC-1-40); TH287/3-aminopiperidine-2,6-dione pretreatment (concentrations unspecified)
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Incubation Time:6 h (LC-1-40 incubation); 2 h (TH287/3-aminopiperidine-2,6-dione pretreatment)
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Result:Induced NUDT1 loss that was efficiently rescued by both TH287 and 3-aminopiperidine-2,6-dione.
Induced NUDT1 degradation that was rescued by MG132 (a 26S proteasome inhibitor).
Parmacokinetics
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NPG (female; 6-week-old; MYCN-amplified T409 primary neuroblastoma patient-derived xenograft)[1]
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Dosage:30 mg/kg
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Administration:i.p.; daily
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Result:Caused remarkable intratumoral NUDT1 depletion within 1 h after a single i.p. dose.
Selectively impeded the growth of MYCN-amplified T409 tumors.
Led to increased intratumoral nucleotide damage and apoptosis, as quantified by 8-oxo-dG and cleaved-Caspase 3 staining.
Was well tolerated, with body weight sustained over the administration period.
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Animal Model:NPG (female; 6-week-old; MYCN-nonamplified T423 primary neuroblastoma patient-derived xenograft)[1]
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Dosage:30 mg/kg
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Administration:i.p.; daily
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Result:Achieved similar NUDT1 depletion in MYCN-nonamplified T423 tumors.
Exhibited minimal effect on tumor growth.
Was well tolerated, with body weight sustained over the administration period.
Chemical Information
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Appearance Solid
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Peso molecular 844.96
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Fòrmula C49H48N8O6
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Color Light yellow to yellow
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SMILES
O=C1CCC(C(N1)=O)N2C(C3=C(C2=O)C=C(C=C3)N4CCN(CC4)CC5CCN(CC5)C(C6=CC=C(C=C6)C7=CC=C8N=CC(C(NC9CC9)=O)=C(C8=C7)NC%10=CC=CC=C%10)=O)=O
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvente y solubilidad
In Vitro:
DMSO : 100 mg/mL (118.35 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 5 mg/mL (5.92 mM); Clear solution
This protocol yields a clear solution of ≥ 5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (50.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Pureza y Documentación
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Ficha de datos (275 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Instrucciones de manejo (2659 KB)
Referencias
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
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| DMSO | 1 mM | 1.1835 mL | 5.9174 mL | 11.8349 mL | 29.5872 mL |
| 5 mM | 0.2367 mL | 1.1835 mL | 2.3670 mL | 5.9174 mL | |
| 10 mM | 0.1183 mL | 0.5917 mL | 1.1835 mL | 2.9587 mL | |
| 15 mM | 0.0789 mL | 0.3945 mL | 0.7890 mL | 1.9725 mL | |
| 20 mM | 0.0592 mL | 0.2959 mL | 0.5917 mL | 1.4794 mL | |
| 25 mM | 0.0473 mL | 0.2367 mL | 0.4734 mL | 1.1835 mL | |
| 30 mM | 0.0394 mL | 0.1972 mL | 0.3945 mL | 0.9862 mL | |
| 40 mM | 0.0296 mL | 0.1479 mL | 0.2959 mL | 0.7397 mL | |
| 50 mM | 0.0237 mL | 0.1183 mL | 0.2367 mL | 0.5917 mL | |
| 60 mM | 0.0197 mL | 0.0986 mL | 0.1972 mL | 0.4931 mL | |
| 80 mM | 0.0148 mL | 0.0740 mL | 0.1479 mL | 0.3698 mL | |
| 100 mM | 0.0118 mL | 0.0592 mL | 0.1183 mL | 0.2959 mL |
LC-1-40 Related Classifications
HY-158062 Related Classifications
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