2. PROTAC Epigenetics
  3. Molecular Glues DNA Methyltransferase
  4. DNMT1 Degrader-1

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.

For research use only. We do not sell to patients.

DNMT1 Degrader-1

DNMT1 Degrader-1 Chemical Structure

CAS No. : 2962943-72-0

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DNMT1 Degrader-1 Related Antibodies

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Description

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[1].

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.

DNMT1 Degrader-1 Related Antibodies

Western Blot Analysis[1]

Cell Line: MV-4-11 AML cells
Concentration: 0, 50, 100, 200, 400, 600, 800, 1000, 1500, 2000 nM
Incubation Time: 0, 6, 9, 12, 15, 24 h
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.

Cell Cycle Analysis[1]

Cell Line: MV-4-11 and Kasumi-1 AML cells
Concentration: 0.2, 0.5, 1, 2 μM
Incubation Time: 24 h
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
Species Dose Route AUC0-t AUC0-∞ T1/2 Tmax Cmax Bioavailability
Rat[1] 25 mg/kg p.o. 689 ng·h/mL 948 ng·h/mL 9.9 μg·h/mL 2.2 h 59.8 ng/mL 61 %
Rat[10] 10 mg/kg i.v. 546 ng·h/mL 613 ng·h/mL 6.6 h / / /
In Vivo

DNMT1 Degrader-1 (40 mg/kg; i.p.; once daily; for 16 consecutive days) significantly inhibits the growth of acute myeloid leukemia and prolongs survival in MV‑4‑11 cell-derived xenograft, WEHI‑3 orthotopic transplantation, and acute myeloid leukemia (AML) patient-derived xenograft mouse models[1].
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.

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]
Dosage: 40 mg/kg
Administration: i.p.; daily; 16 days
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.
Molecular Weight

408.54

Formula

C24H32N4O2
CAS No.
SMILES

COC1=CC2=NC(C3=CCCC3)=NC(N4CCC(N5CCCC5)CC4)=C2C=C1OC
Shipping

Room temperature in continental US; may vary elsewhere.
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Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
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DNMT1 Degrader-1 Related Classifications

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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

DNMT1 Degrader-12962943-72-0Molecular GluesDNA MethyltransferaseDNMTsDNA MTasesG9aUHRF1DNMT3BDNMT3Aacute myeloid leukemiaKasumi-1 AML cellsMV-4-11 AML cellsDNMT1proteasome pathwaypatient-derived xenograft modelsInhibitorinhibitorinhibit

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