LYG-409
Based on 1 Customer Validation
LYG-409 is a highly potent, selective, and orally active GSPT1 molecular glue degrader. LYG-409 induces GSPT1 degradation in KG-1 cells with a DC50 of 7.87 nM. LYG-409 binds to Cereblon with an IC50 of 191 nM, promotes the formation of the CRBN-GSPT1 ternary complex, and induces proteasome-dependent degradation of GSPT1. LYG-409 exhibits broad antiproliferative and GSPT1-degrading activities in a variety of hematologic and solid tumor cells. LYG-409 can be used for studies related to GSPT1-targeted protein degradation, acute myeloid leukemia, and prostate cancer.
Para uso exclusivo en investigación. No vendemos a pacientes.
- Pureza: 98.11%
- No. CAS: 3053857-55-6
- Fòrmula: C25H20F3N3O6
- Peso molecular:515.44
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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
- Pureza y Documentación
- Referencias
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Help & FAQs
Ver todos los productos específicos de isoformas Eukaryotic Release Factor (eRF)
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Actividad biológica
Descripciòn
IC50 & Target
[1]|
eRF3a/GSPT1 7.87 nM (DC50) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| MV4-11 | IC50 |
0.008 μM
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Antiproliferative activity against human cancer MV4-11 cells assessed as reduction in cell proliferation incubated for 72 hrs by CCK-8 assay.
Antiproliferative activity against human cancer MV4-11 cells assessed as reduction in cell proliferation incubated for 72 hrs by CCK-8 assay.
|
39854008 |
| OCI-AML-3 | IC50 |
0.084 μM
|
Antiproliferative activity against human cancer OCI-AML3 cells assessed as reduction in cell proliferation incubated for 72 hrs by CCK-8 assay.
Antiproliferative activity against human cancer OCI-AML3 cells assessed as reduction in cell proliferation incubated for 72 hrs by CCK-8 assay.
|
39854008 |
| U-937 | IC50 |
0.029 μM
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Antiproliferative activity against human cancer U937 cells assessed as reduction in cell proliferation incubated for 72 hrs by CCK-8 assay.
Antiproliferative activity against human cancer U937 cells assessed as reduction in cell proliferation incubated for 72 hrs by CCK-8 assay.
|
39854008 |
| SU-DHL-4 | IC50 |
0.34 μM
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Antiproliferative activity against human cancer SU-DHL-4 cells assessed as reduction in cell proliferation incubated for 72 hrs by CCK-8 assay.
Antiproliferative activity against human cancer SU-DHL-4 cells assessed as reduction in cell proliferation incubated for 72 hrs by CCK-8 assay.
|
39854008 |
| WSUDLCL2 | IC50 |
0.017 μM
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Antiproliferative activity against human cancer WSU-DLCL2 cells assessed as reduction in cell proliferation incubated for 72 hrs by CCK-8 assay.
Antiproliferative activity against human cancer WSU-DLCL2 cells assessed as reduction in cell proliferation incubated for 72 hrs by CCK-8 assay.
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39854008 |
| 22Rv1 | IC50 |
0.030 μM
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Antiproliferative activity against human cancer 22Rv1 cells assessed as reduction in cell proliferation incubated for 72 hrs by CCK-8 assay.
Antiproliferative activity against human cancer 22Rv1 cells assessed as reduction in cell proliferation incubated for 72 hrs by CCK-8 assay.
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39854008 |
| T47D | IC50 |
0.047 μM
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Antiproliferative activity against human cancer T47D cells assessed as reduction in cell proliferation incubated for 72 hrs by CCK-8 assay.
Antiproliferative activity against human cancer T47D cells assessed as reduction in cell proliferation incubated for 72 hrs by CCK-8 assay.
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39854008 |
| MDA-MB-231 | IC50 |
0.016 μM
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Antiproliferative activity against human cancer MDA-MB-231 cells assessed as reduction in cell proliferation incubated for 72 hrs by CCK-8 assay.
Antiproliferative activity against human cancer MDA-MB-231 cells assessed as reduction in cell proliferation incubated for 72 hrs by CCK-8 assay.
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39854008 |
| MDA-MB-453 | IC50 |
0.046 μM
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Antiproliferative activity against human cancer MDA-MB-453 cells assessed as reduction in cell proliferation incubated for 72 hrs by CCK-8 assay.
Antiproliferative activity against human cancer MDA-MB-453 cells assessed as reduction in cell proliferation incubated for 72 hrs by CCK-8 assay.
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39854008 |
| Hs-578T | IC50 |
0.081 μM
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Antiproliferative activity against human cancer Hs578t cells assessed as reduction in cell proliferation incubated for 72 hrs by CCK-8 assay.
Antiproliferative activity against human cancer Hs578t cells assessed as reduction in cell proliferation incubated for 72 hrs by CCK-8 assay.
|
39854008 |
| BEAS-2B | IC50 |
0.37 μM
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Antiproliferative activity against human normal lung epithelial BEAS-2B cells assessed as reduction in cell proliferation incubated for 72 hrs by CCK-8 assay.
Antiproliferative activity against human normal lung epithelial BEAS-2B cells assessed as reduction in cell proliferation incubated for 72 hrs by CCK-8 assay.
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39854008 |
In Vitro
LYG-409 (4 h) induces time- and dose-dependent degradation of GSPT1 via the ubiquitin-proteasome pathway in KG-1 acute myeloid leukemia cells, with a DC50 of 7.87 nM[1].
LYG-409 (200 nM; 72 h) potently inhibits the proliferation of KG-1 acute myeloid leukemia cells, with an IC50 of 9.50 nM, and induces 92.39% GSPT1 degradation at a concentration of 200 nM[1].
LYG-409 (72 h) inhibits the proliferation of various hematologic and solid tumor cells, with IC50 values of 0.010, 0.008, 0.029, 0.017, 0.030, and 0.016 μM against KG-1, MV4-11, U937, WSU-DLCL2, 22Rv1, and MDA-MB-231 cells, respectively[1].
LYG-409 (at multiple concentrations; 4-24 h) induces dose-dependent GSPT1 degradation in a variety of hematological and solid tumor cell lines, with DC50 values ranging from 2.77 nM (22Rv1) to 90 nM (Molm-13)[1].
LYG-409 (191 nM) binds to human CRBN with high affinity, with an IC50 of 191 nM[1].
LYG-409 (100 nM; 2-12 h) reduces GSPT1 protein levels in a time-dependent manner in KG-1 cells, accompanied by a decrease in C-MYC protein levels[1].
LYG-409 (1-10 μM) does not inhibit CYP3A4 at the concentration of 10 μM, exhibits moderate hERG inhibitory activity, has acceptable permeability, and shows a high plasma protein binding rate (99.03%)[1].
LYG-409 (24 h) induces dose-dependent degradation of GSPT1 in 22Rv1, MDA-MB-453, MDA-MB-231 and Hs578t cells, with DC50 values of 2.77, 4.05, 6.73 and 7.37 nM, respectively[1].
LYG-409 (10-200 nM; 12 h) induces concentration-dependent apoptosis in KG-1 acute myeloid leukemia cells, with 75.9% apoptotic cells observed after treatment with 200 nM for 12 h[1].
LYG-409 induces GSPT1 degradation in a concentration-dependent manner in MV4-11 and Molm-13 cells, with DC50 values of 16 nM and 90 nM at 4 h, respectively[1].
LYG-409 (4 h) promotes the formation of the CRBN-GSPT1 ternary complex in a concentration-dependent manner in HEK293T cells expressing SmBiT-CRBN and LgBiT-GSPT1[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:human acute myeloid leukemia KG-1 cells
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Concentration:200 nM
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Incubation Time:72 h
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Result:Induced 92.39% degradation of GSPT1 protein in KG-1 cells.
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Cell Line:human acute myeloid leukemia KG-1 cells
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Concentration:10 nM; 50 nM; 200 nM
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Incubation Time:12 h
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Result:Resulted in 22.4% early and late apoptotic cells at 10 nM.
Resulted in 46.8% early and late apoptotic cells at 50 nM.
Resulted in 75.9% early and late apoptotic cells at 200 nM.
Parmacokinetics
| Species | Dose | Route | Cmax | Tmax | AUClast | AUCinf | T1/2 | MRTINF_obs | F | CL | C0 | Vss_obs |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Rat[1] | 2 mg/kg | i.v. | / | / | / | 4349 ng·h/mL | 1.53 h | / | / | 8.1 mL/min/kg | / | / |
| Rat[1] | 10 mg/kg | p.o. | 3460 ng/mL | 0.33 h | / | 4978 ng·h/mL | 3.71 h | / | 22.93 % | / | / | / |
| Mice[1] | 2 mg/kg | i.v. | / | / | 8812 ng·h/mL | 8823 ng·h/mL | 1.12 h | 1.07 h | / | 3.8 mL/min/kg | 16143 ng/mL | 0.24 L/kg |
| Mice[1] | 10 mg/kg | p.o. | 2550 ng/mL | 0.41 h | 6147 ng·h/mL | 6406 ng·h/mL | 1.82 h | 2.91 h | 13.9 % | / | / | / |
| Dog[1] | 2 mg/kg | i.v. | / | / | 2170 ng·h/mL | 2170 ng·h/mL | 1.01 h | 0.59 h | / | 16.9 mL/min/kg | 9030 ng/mL | 0.54 L/kg |
| Dog[1] | 10 mg/kg | p.o. | 247 ng/mL | 0.50 h | 391 ng·h/mL | 442 ng·h/mL | 4.58 h | 2.64 h | 3.6 % | / | / | / |
In Vivo
LYG-409 (60 mg/kg/day; p.o.; once daily; 18 days) achieves a TGI of 104.49% in the 22Rv1 prostate cancer xenograft model of male Balb/c nude mice. At the end of the study, 87.5% (7/8) of the mice achieve complete remission, with no significant changes observed in behavior, diet or body weight[1].
LYG-409 (60 mg/kg; single oral gavage) reduces the GSPT1 protein level in tumor tissues by more than 70% at 6 h post-administration in 22Rv1 xenograft mice, and the GSPT1 level remains below 50% of that in the control group at 24 h[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c nude (female, 4-6 weeks old, 16-20 g, subcutaneously injected with 1 × 107 MV4−11 cells)[1]
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Dosage:5 mg/kg; 15 mg/kg; 30 mg/kg
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Administration:p.o.; daily; 14 days
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Result:Showed no significant tumor growth inhibition at 5 mg/kg.
Achieved a tumor growth inhibition (TGI) rate of 75.29% at 15 mg/kg.
Achieved a TGI rate of 94.34% at 30 mg/kg.
Caused no significant body weight loss, mortality, or tissue injuries in any dose group.
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Animal Model:BALB/c nude (male, 4-6 weeks old, 16-20 g, subcutaneously injected with 5 × 106 22Rv1 cells)[1]
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Dosage:60 mg/kg (daily dosing); 60 mg/kg (single dose)
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Administration:p.o. (daily for 18 days); p.o. (single dose)
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Result:Achieved a TGI rate of 104.49% with 87.5% of mice showing complete tumor response at 60 mg/kg daily.
Reduced GSPT1 protein levels by >70% at 6 h post-administration, and levels remained below 50% of control at 24 h after a single 60 mg/kg dose.
Caused no significant body weight loss or changes in behavior/diet during 18 days of administration.
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Animal Model:Sprague-Dawley (SD) (male and female, weight matching across groups)[1]
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Dosage:100 mg/kg; 200 mg/kg; 400 mg/kg
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Administration:p.o.; daily; 7 days
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Result:Caused no mortality, significant changes in vital signs, or organ structure/morphology abnormalities in any dose group.
Induced a transient decrease in cholesterol levels in the 100 mg/kg group.
Led to an increase in potassium levels after 7 days of withdrawal from 400 mg/kg treatment.
Chemical Information
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No. CAS 3053857-55-6
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Appearance Solid
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Peso molecular 515.44
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Fòrmula C25H20F3N3O6
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Color White to off-white
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SMILES
O=C1N(CC2=C1C=CC(CNC(C3=CC4=C(OC3)C=CC(OC(F)(F)F)=C4)=O)=C2)C5CCC(NC5=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 (194.01 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 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 5 mg/mL (9.70 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 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
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 (284 KB)
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SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Korean - KR (251 KB)
- Portuguese - PT (251 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 |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.9401 mL | 9.7005 mL | 19.4009 mL | 48.5023 mL |
| 5 mM | 0.3880 mL | 1.9401 mL | 3.8802 mL | 9.7005 mL | |
| 10 mM | 0.1940 mL | 0.9700 mL | 1.9401 mL | 4.8502 mL | |
| 15 mM | 0.1293 mL | 0.6467 mL | 1.2934 mL | 3.2335 mL | |
| 20 mM | 0.0970 mL | 0.4850 mL | 0.9700 mL | 2.4251 mL | |
| 25 mM | 0.0776 mL | 0.3880 mL | 0.7760 mL | 1.9401 mL | |
| 30 mM | 0.0647 mL | 0.3233 mL | 0.6467 mL | 1.6167 mL | |
| 40 mM | 0.0485 mL | 0.2425 mL | 0.4850 mL | 1.2126 mL | |
| 50 mM | 0.0388 mL | 0.1940 mL | 0.3880 mL | 0.9700 mL | |
| 60 mM | 0.0323 mL | 0.1617 mL | 0.3233 mL | 0.8084 mL | |
| 80 mM | 0.0243 mL | 0.1213 mL | 0.2425 mL | 0.6063 mL | |
| 100 mM | 0.0194 mL | 0.0970 mL | 0.1940 mL | 0.4850 mL |
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