DNMT3 Inhibitor

Decitabine (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.

SGI-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.

Zebularine (NSC309132; 4-Deoxyuridine) is a DNA methyltransferase inhibitor. Zebularine also inhibits cytidine deaminase with a K_i of 0.95 μM.

DY-46-2 is a high potency and selectivity novel non-nucleoside DNA methyltransferase 3A (DNMT3A) inhibitor with an IC₅₀ value of 0.39 μM.

CM-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.

DNMT-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.

DNMT3A-IN-4 is a DNMT3A inhibitor with an IC₅₀ of 33.4 μM against human DNMT3A. DNMT3A-IN-4 inhibits the proliferation of colorectal cancer cells and can be used for the research of colorectal cancer.

DNMT3A-IN-1 (compound 1) is an effective and selective DNMT3A inhibitor. DNMT3A-IN-1 exhibits inhibitory activity against DNMT3A, with K_I 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).

Nanaomycin 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.

γ-Oryzanol is a potent DNA methyltransferases (DNMTs) inhibitor in the striatum of mice. γ-Oryzanol significantly inhibits the activities of DNMT1 (IC₅₀=3.2 μM), DNMT3a (IC₅₀=22.3 μM).

CM-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.

CM-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.

DNMT1-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.

(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.

DNMT-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.

Go 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.

CM-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.