DNMT3
DNMT3A is a de novo DNA methyltransferase that catalyzes CpG methylation and establishes epigenetic patterns required for mammalian development, cellular differentiation, genomic imprinting, and stable gene regulation[1][1]. Mechanistically, DNMT3A functions within the DNA methylation machinery that creates new methylation marks on previously unmethylated DNA, thereby contributing to transcriptional repression and maintenance of cellular identity[1][2]. During development, DNMT3A and DNMT3B share partially overlapping functions; however, locus-specific analyses demonstrated that DNMT3A is uniquely required for de novo methylation of Polycomb group target developmental genes, whereas DNMT3B shows distinct targeting preferences, including a dominant role at specific X-chromosomal regions[2]. In disease models, disruption of DNMT3A alters epigenetic regulation and impairs hematopoietic stem cell differentiation, leading to enhanced stem cell self-renewal and abnormal lineage commitment[3]. Consistent with these findings, DNMT3A is among the most frequently mutated epigenetic regulators in acute myeloid leukemia, highlighting its importance in hematopoietic homeostasis and leukemogenesis[2][4]. Compared with related isoforms, DNMT3A1 and DNMT3A2 display distinct genomic localization patterns; notably, DNMT3A1 preferentially localizes to methylated shores of bivalent CpG island promoters and contributes to DNA methylation fidelity at these regulatory regions[7]. For experimental applications, DNMT3A serves as a widely used model for investigating de novo DNA methylation, epigenetic inheritance, developmental gene regulation, and mutation-driven hematologic malignancies[2][3][7].
Références:
- [1]. Roll C, et al. Solution structures of a duplex containing an adenine opposite a gap (absence of one nucleotide). An NMR study and molecular dynamic simulations with explicit water molecules. Eur J Biochem. 1999 Aug;264(1):120-31. [Content Brief]
- [2]. Yagi M, et al. Identification of distinct loci for de novo DNA methylation by DNMT3A and DNMT3B during mammalian development. Nat Commun. 2020 Jun 24;11(1):3199. [Content Brief]
- [3]. Challen GA, et al. Dnmt3a is essential for hematopoietic stem cell differentiation. Nat Genet. 2011 Dec 4;44(1):23-31. [Content Brief]
- [4]. Kiros M, et al. Trends in HIV-1 pretreatment drug resistance and HIV-1 variant dynamics among antiretroviral therapy-naive Ethiopians from 2003 to 2018: a pooled sequence analysis. Virol J. 2023 Oct 25;20(1):243. [Content Brief]
All Product Categories
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DNMT3 Produits associés (18)
Produits associés (18)
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Anticorps (1)
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Decitabine
0 ImagesSynonyms: 5-Aza-2'-deoxycytidine; 5-AZA-CdR; NSC 127716Decitabine (NSC 127716) is an orally active deoxycytidine analogue antimetabolite and DNA methyltransferase inhibitor. Decitabine incorporates into DNA in place of cytosine can covalently trap DNA methyltransferase to DNA causing irreversible inhibition of the enzyme. Decitabine induces cell G2/M arrest and cell Apoptosis. Decitabine has potent anticancer activity.
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SGI-1027
0 ImagesSGI-1027 is a DNA methyltransferase (DNMT) inhibitor, with IC50s of 7.5 μM, 8 μM, and 12.5 μM for DNMT3B, DNMT3A, and DNMT1 with poly(dI-dC) as substrate.
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Zebularine
0 ImagesZebularine (NSC309132; 4-Deoxyuridine) is a DNA methyltransferase inhibitor. Zebularine also inhibits cytidine deaminase with a Ki of 0.95 μM.
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DY-46-2
0 ImagesDY-46-2 is a high potency and selectivity novel non-nucleoside DNA methyltransferase 3A (DNMT3A) inhibitor with an IC50 value of 0.39 μM.
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CM-272
0 ImagesCM-272 is a first-in-class, potent, selective, substrate-competitive and reversible dual G9a/DNA methyltransferases (DNMTs) inhibitor with antitumor activities. CM-272 inhibits G9a, DNMT1, DNMT3A, DNMT3B and GLP with IC50s of 8 nM, 382 nM, 85 nM, 1200 nM and 2 nM, respectively. CM-272 inhibits cell proliferation and promotes apoptosis, inducing IFN-stimulated genes and immunogenic cell death.
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MS1129
0 ImagesCat. No.: HY-181955MS1129 is a DNMT degrader that induces proteasomal degradation of DNMT1, DNMT3A and DNMT3B proteins. MS1129 upregulates TRAIL, DR4 and DR5 proteins, downregulates the decoy receptor DcR2, and activates TRAIL-dependent apoptosis via the HIF-1/2 and Caspase-10 pathways. MS1129 is applicable to the research of VHL-deficient clear cell renal cell carcinoma.
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DNMT-IN-6
0 ImagesCat. No.: HY-182009CAS No.: 3038316-36-5DNMT-IN-6 is a DNA methyltransferase inhibitor with activity against DNMT1, DNMT3A, and DNMT3B. DNMT-IN-6 drives demethylation, and restores TMS1 tumor suppressor gene expression. DNMT-IN-6 induces apoptosis, causes G2/M phase arrest, disrupts mitochondrial integrity, and activates the intrinsic caspase cascade (3/7/9). DNMT-IN-6 inhibits tumor growth, and improves survival in xenograft models. DNMT-IN-6 can be used for the research of cancer, such as diffuse large B-cell lymphoma.
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DNMT3A-IN-1
0 ImagesDNMT3A-IN-1 (compound 1) is an effective and selective DNMT3A inhibitor. DNMT3A-IN-1 exhibits inhibitory activity against DNMT3A, with KI values ranging from 9.16 to 18.85 μM (AdoMet) and 11.37 to 23.34 μM (poly dI-dC). DNMT3A-IN-1 can induce apoptosis in acute myeloid leukemia (AML) cell lines (Apoptosis).
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Nanaomycin A
0 ImagesNanaomycin A is a selective DNMT3B inhibitor with an IC50 of 500 nM. Nanaomycin A inhibits the in vitro growth of human Plasmodium falciparum with an IC80 of 33.1 nM.
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CM-579 trihydrochloride
0 ImagesCat. No.: HY-117421ACAS No.: 2448471-08-5CM-579 trihydrochloride is a first-in-class reversible, dual inhibitor of G9a and DNMT, with IC50 values of 16 nM, 32 nM for G9a and DNMT, respectively. Has potent in vitro cellular activity in a wide range of cancer cells.
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CM-579
0 ImagesCat. No.: HY-117421CAS No.: 1846570-40-8CM-579 is a first-in-class reversible, dual inhibitor of G9a and DNMT, with IC50 values of 16 nM, 32 nM for G9a and DNMT, respectively. Has potent in vitro cellular activity in a wide range of cancer cells.
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DNMT1-IN-5
0 ImagesCat. No.: HY-172217CAS No.: 2982511-19-1DNMT1-IN-5 (Compound 55) is the inhibitor for DNMT that inhibits DNMT1 and DNMT3A with IC50 of 2.42 μM and 14.4 μM. DNMT1-IN-5 exhibits antiproliferative activity in a variety of cancer cell lines (IC50s for TMD-8, DOHH2, MOLM-13, THP-1, RPIM-8226 and HCT116 are 0.19-2.37 μM), arrests the cell cycle at G2/M phase, and induces apoptosis in TMD-8 and DOHH2 cells. DNMT1-IN-5 exhibits antitumor efficacy in TMD-8 xenograft mouse models.
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(4aS,8aR)-NPD-001
0 ImagesCat. No.: HY-150025CAS No.: 2366272-43-5(4aS,8aR)-NPD-001 is a potent and allosteric inhibitor of DNMT3A. (4aS,8aR)-NPD-001 inhibits DNMT3A activity by disrupting protein-protein interactions. (4aS,8aR)-NPD-001 induces apoptosis of acute myeloid leukemia (AML) cell lines. (4aS,8aR)-NPD-001 induces differentiation of distinct AML cell lines including cells with mutated DNMT3A R882.
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DNMT-IN-5
0 ImagesCat. No.: HY-176230CAS No.: 3126555-64-1DNMT-IN-5 is a stable and efficient DNA methyltransferase (DNMT) inhibitor with high stability and high activity with an IC50 of 0.78 nM. DNMT-IN-5 exhibits sub-micromolar DNMT3A inhibitory activity, upregulates the expression of DNMT-targeted genes, impairs cell proliferation, and triggers a critical cell cycle arrest. DNMT-IN-5 can be used for the study of p53-depleted colorectal cancer.
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Go 6983 (GMP)
0 ImagesCat. No.: HY-13689GCAS No.: 133053-19-7Go 6983 GMP is Go 6983 (HY-13689) produced by using GMP guidelines. GMP small molecules works appropriately as an auxiliary reagent for cell therapy manufacture. Go 6983 is a dual inhibitor targeting Suv39h1/2 (KMT1A/KMT1B) and PKC, as well as a transcriptional activator capable of inducing DNA hypomethylation. Go 6983 stimulates the transcription of Prdm14 by reducing Suv39h1/2 protein levels, decreasing histone modifications in the Prdm14 promoter region, and increasing the recruitment of RNA polymerase II. Go 6983 induces genome-wide DNA hypomethylation by inhibiting de novo methyltransferase expression and increasing Tet1/Tet2 levels, thereby promoting self-renewal and pluripotency maintenance of stem cells. Meanwhile, Go 6983 can block PKC-mediated signaling pathways to reduce the expression of EMT-related genes and eliminate the upregulation of antioxidant genes downstream of NRF2. Go 6983 is mainly used in mechanism studies related to myocardial ischemia/reperfusion injury.
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CM-444
0 ImagesCat. No.: HY-163803CAS No.: 2256079-52-2CM-444 is inhibitor for HDAC (IC50 is 6 nM-0.6 μM) and DNA methyltransferases (DNMT, IC50 is 1.8-2.3 μM). CM-444 is an inducer for the differentiation of acute myeloid leukemia cells. CM-444 exhibits anti-leukemic activity and improves the survival rate in mouse models.
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