dnmt1 inhibitor

SW155246 is a potent and selective inhibitor of DNMT1 (DNA methyltransferase 1; IC50 of 1.2 μM). SW155246 induces re-expression of the tumor suppressor geneRASSF1 in A549 cells.

GSK3685032 is a time-independent, non-covalent, selective, and reversible DNMT1 inhibitor with an IC₅₀ of 0.036 μM. GSK3685032 induces loss of DNA methylation, transcriptional activation, and inhibition of cancer cell growth, and can be used in cancer therapy research.

GSK-3484862 is a non-covalent Dnmt1 inhibitor that induces DNA hypomethylation, offering potential therapeutic benefits against cancer.

Genipin ((+)-Genipin), an active aglycone derived from an iridoid glycoside called geniposide, is found in the fruit of Gardenia jasminoides Ellis.

6-Thioguanine (2-Amino-6-purinethiol) is an antineoplastic compound which also has antimetabolite action. The drug is used in the therapy of acute leukemia.

EML741 also inhibits DNMT1 (IC50, 3.1 μM), with no effect on DNMT3a or DNMT3b. EML741 exhibits low cell toxicity, and is membrane permeable and blood-brain barrier penetrated. EML741 is a histone lysine methyltransferase G9a/GLP inhibitor, with an IC50 of 23 nM, Kd of 1.13 μM for G9a.

Isofistularin-3, a direct DNA-competitive DNMT1 inhibitor with an IC50 of 13.5 μM, functions as a DNA demethylating agent, leading to cell cycle arrest and increased sensitivity to TRAIL in cancer cells. Additionally, it can be employed as an ADC cytotoxin.

NSC232003 is a highly potent and cell-permeable inhibitor of [UHRF1].

DC-05 is an inhibitor of DNA methyltransferase 1 (DNMT1) (IC50 and a Kd: 10.3 μM and 1.09 μM, respectively).

DC_517 is an inhibitor of DNA methyltransferase 1 (DNMT1) ( IC50: 1.7 μM; Kd: 0.91 μM).

RX-3117 (fluorocyclopentenylcytosine) is a novel a cytidine analog. RX-3117 displays anticancer activity in several cancer cell lines, including gemcitabine-resistant variants.

SGI-1027 (DNA Methyltransferase Inhibitor II) is an effective and selective inhibitor of DNA methyltransferase (DNMT). The IC50 of SGI-1027(SGI1027) against DNMT1, DNMT3A, and DNMT3B are 6, 8, 7.5 μM, respectively.

DNMT1/HDAC-IN-1 (compound (R)-23a), a potent dual inhibitor targeting both DNMT1 and HDAC, exhibits impressive inhibitory effects specifically on HDAC1 (HDAC1:IC50=0.05 μM), a major HDAC isoform that interacts with DNMT1 across multiple protein complexes involved in the transcriptional silencing of TSGs. This compound has been shown to remodel the tumor immune microenvironment and induce tumor regression, effectively reversing cancer-specific epigenetic abnormalities.

MC3343, a DNMT inhibitor with IC50 values of 5.7 μM for DNMT1 and 1.7 μM for DNMT3a, affects tumor proliferation by blocking osteosarcoma cells in the G1 or G2/M phase and induces osteogenic differentiation by specifically re-expressing genes that regulate this physiological process, and is able to show synergistic effects in combination with adriamycin and cisplatin (CDDP).

DNMT1-IN-5 (Compound 55) is an inhibitor of DNMT, specifically targeting DNMT1 and DNMT3A, with IC50 values of 2.42 μM and 14.4 μM, respectively. It demonstrates antiproliferative effects across various cancer cell lines (TMD-8, DOHH2, MOLM-13, THP-1, RPIM-8226, and HCT116) with IC50 values ranging from 0.19 to 2.37 μM. The compound induces G2/M phase cell cycle arrest and apoptosis in TMD-8 and DOHH2 cells. Additionally, DNMT1-IN-5 exhibits antitumor efficacy in a TMD-8 xenograft mouse model.

(Rac)-RG108 (NSC401077) is an inhibitor of DNMT1, effectively blocking DNA methyltransferases.

METTL3-IN-11 is a highly selective METTL3 inhibitor (IC50 = 45.31 nM), demonstrating greater selectivity for METTL3 over DNMT1, EZH1, MLL1, and PRMT1. It reduces m6A levels in total RNA of MOLM-13 and SKOV3 cells, inducing apoptosis and inhibiting migration. METTL3-IN-11 also decreases expression of m6A downstream target genes (c-MYC and BCL2). It is applicable in ovarian cancer and acute myeloid leukemia research.

MC3817 is a selective DNMT inhibitor, with IC50 values of 0.044 μM for DNMT1 and greater than 10 μM for DNMT3A/3L. It inhibits P53-dependent cancer cell proliferation, induces apoptosis and DNA damage, and elevates the levels of cleaved Caspase 3, P53, and γH2AX. MC3817 is applicable in research on non-small cell lung cancer, colon cancer, cervical cancer, triple-negative breast cancer, and histiocytic lymphoma.

MC3817 free base is a selective DNMT inhibitor with an IC50 value of 0.044 μM for DNMT1 and greater than 10 μM for DNMT3A/3L. It suppresses P53-dependent cancer cell proliferation, induces apoptosis and DNA damage, and increases the levels of cleaved Caspase 3, P53, and γH2AX. MC3817 free base is applicable in research related to non-small cell lung cancer, colon cancer, cervical cancer, triple-negative breast cancer, and histiocytic lymphoma.

DNMT-IN-6 is a DNA methyltransferase inhibitor effective against DNMT1, DNMT3A, and DNMT3B. It promotes demethylation and restores the expression of the TMS1 tumor suppressor gene. DNMT-IN-6 induces apoptosis, causes G2/M phase arrest, disrupts mitochondrial integrity, and activates endogenous caspase cascades (3/7/9). Additionally, it inhibits tumor growth and enhances survival rates in xenograft models. DNMT-IN-6 is applicable in cancer research, including studies on diffuse large B-cell lymphoma.

(R)-GSK-3685032 is the R-enantiomer of GSK-3685032, a first-in-class, non-time-dependent, non-covalent, reversible, selective DNMT1 inhibitor with an IC50 of 0.036 μM, which induces robust loss of DNA methylation, transcriptional activation, and inhibition of cancer cell growth.

Procainamide (Novocainamide) is a specific and potent DNA methyltransferase 1 (DNMT1) inhibitor and a Class 1A antiarrhythmic agent, with potential applications in cancer and arrhythmia research [1] [2].

CM-272 is a dual G9a/DNA methyltransferases (DNMTs) inhibitor.

USP7-IN-9, a potent inhibitor of ubiquitin-specific protease 7 (USP7) with an IC50 of 40.8 nM, effectively induces apoptosis and arrests cell progression at the G0/G1 and S phases in RS4;11 cells. It decreases the protein levels of oncoproteins MDM2 and DNMT1 while enhancing the levels of tumor suppressors p53 and p21.