DNMT1 Degrader-1
Based on 1 Customer Validation
DNMT1 Degrader-1 is a selective DNMT1 degrader with an IC50 of 202.87 nM and a Kd value of 122 nM. As a molecular glue, DNMT1 Degrader-1 forms a ternary complex with DNMT1 and UHRF1, thereby triggering UHRF1-mediated ubiquitination and degradation of DNMT1, and inhibiting the enzymatic activity of DNMT1. DNMT1 Degrader-1 inhibits the proliferation of primary acute myeloid leukemia cells and exerts anti-tumor activity. DNMT1 Degrader-1 can be used for the research of acute myeloid leukemia.
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- Pureté : 99.47%
- CAS No.: 2962943-72-0
- Formule: C24H32N4O2
- Masse moléculaire:408.54
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Stockage:Powder -20°C, 3 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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Activité biologique
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Chemical Information
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Solvant et solubilité
- Pureté et documentation
- Références
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Help & FAQs
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Activité biologique
Description
IC50 & Target
[1]|
DNMT1 |
In Vitro
DNMT1 Degrader-1 (compound 6k) (0-2000 nM; 0-24 h) induces time- and concentration-dependent degradation of DNMT1 protein in MV-4-11 acute myeloid leukemia (AML) cells, with a DC50 of 123.4 nM[1].
DNMT1 Degrader-1 (0.25-1 μM; 24 h) does not affect DNMT1 mRNA levels in Kasumi-1 or MV-4-11 AML cells[1].
DNMT1 Degrader-1 (1 μM; 6 h) induces ubiquitination of DNMT1 protein in MV-4-11 acute myeloid leukemia (AML) cells, thereby leading to its proteasomal degradation[1].
The effect of DNMT1 Degrader-1 (1 μM; 0-24 h) on inducing ubiquitination and degradation of DNMT1 in MV-4-11 acute myeloid leukemia (AML) cells is dependent on UHRF1[1].
DNMT1 Degrader-1 (72 h) inhibits the proliferation of various AML and hematological cancer cell lines[1].
DNMT1 Degrader-1 (0.2-2 μM; 24 h) induces dose-dependent cell cycle arrest in MV-4-11 and Kasumi-1 acute myeloid leukemia (AML) cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MV-4-11 AML cells
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Concentration:0, 50, 100, 200, 400, 600, 800, 1000, 1500, 2000 nM
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Incubation Time:0, 6, 9, 12, 15, 24 h
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Result:Induced time-dependent degradation of DNMT1 protein, with complete elimination observed by 24 h at 1 μM.
Induced concentration-dependent DNMT1 degradation with a DC50 of 123.4 nM after 24 h treatment.
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Cell Line:MV-4-11 and Kasumi-1 AML cells
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Concentration:0.2, 0.5, 1, 2 μM
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Incubation Time:24 h
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Result:Induced dose-dependent G1 phase accumulation with reduced cell numbers in S and G2/M phases in MV-4-11 cells.
Induced dose-dependent S phase accumulation with reduced cell numbers in G1 and G2/M phases in Kasumi-1 cells.
Parmacokinetics
In Vivo
DNMT1 Degrader-1 (40 mg/kg; i.p.; daily administration; consecutive 14 days) exhibits extremely low in vivo hematological toxicity in healthy BALB/c mice following 14 days of daily intraperitoneal injection[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 mice (18-22 g, 6-8 weeks) with MV‑4‑11 subcutaneous xenografts or WEHI‑3 orthotopic transplantation; NOG mice (16-20 g, 6 weeks) with AML patient‑derived xenografts[1]
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Dosage:40 mg/kg
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Administration:i.p.; daily; 16 days
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Result:Markedly inhibited tumor growth in MV‑4‑11 xenograft mice, alleviated leukemia‑induced splenomegaly, reduced leukemic cell infiltration in liver and spleen.
Significantly prolonged the overall survival of WEHI‑3 orthotopic transplantation mice.
Obviously increased the survival rate of AML PDX mice, reduced the population of human CD45+ AML cells in bone marrow and peripheral blood, and showed potent in vivo anti‑AML efficacy with favorable safety.
Chemical Information
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CAS No. 2962943-72-0
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Appearance Solid
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Masse moléculaire 408.54
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Formule C24H32N4O2
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Color Off-white to light yellow
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SMILES
COC1=CC2=NC(C3=CCCC3)=NC(N4CCC(N5CCCC5)CC4)=C2C=C1OC
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Powder -20°C 3 years In solvent -80°C 6 months -20°C 1 month
Solvant et solubilité
In Vitro:
DMSO : 25 mg/mL (61.19 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)
Pureté et documentation
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Fiche technique (280 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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Instruction de manipulation (2659 KB)
Références
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 | 2.4477 mL | 12.2387 mL | 24.4774 mL | 61.1935 mL |
| 5 mM | 0.4895 mL | 2.4477 mL | 4.8955 mL | 12.2387 mL | |
| 10 mM | 0.2448 mL | 1.2239 mL | 2.4477 mL | 6.1194 mL | |
| 15 mM | 0.1632 mL | 0.8159 mL | 1.6318 mL | 4.0796 mL | |
| 20 mM | 0.1224 mL | 0.6119 mL | 1.2239 mL | 3.0597 mL | |
| 25 mM | 0.0979 mL | 0.4895 mL | 0.9791 mL | 2.4477 mL | |
| 30 mM | 0.0816 mL | 0.4080 mL | 0.8159 mL | 2.0398 mL | |
| 40 mM | 0.0612 mL | 0.3060 mL | 0.6119 mL | 1.5298 mL | |
| 50 mM | 0.0490 mL | 0.2448 mL | 0.4895 mL | 1.2239 mL | |
| 60 mM | 0.0408 mL | 0.2040 mL | 0.4080 mL | 1.0199 mL |
DNMT1 Degrader-1 Related Classifications
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