dnmt1

GSK3685032 is a non-covalent and selective DNMT1 inhibitor(IC50 = 36 nM). The inhibitory effect is time-independent and reversible. GSK3685032 induces loss of DNA methylation and transcriptional activation and inhibits cancer cell growth.

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.

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.

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-579 is a dual inhibitor of G9a and DNMT( IC50:16 nM, 32 nM for G9a and DNMT). It has potent in vitro cellular activity in a wide range of cancer cells.

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

γ-Oryzanol (Gamma-Oryzanol) is a natural nutrient extract isolated from rice bran oil that contains a mixture of sterols and ferulic acids, which may aid in the destruction of free radicals in the skin. It has recently been researched for its ability to slow the progress of melanin pigmentation by intercepting the ultraviolet rays at the skin's surface and hindering their transmission.

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.

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.

W4022 (compound 16) is an efficient dual inhibitor of the lysine methyltransferases G9a NSD2, with IC50 values of 0.241 μM for G9a and 0.017 μM for NSD2. It exhibits potent antiproliferative properties, including the ability to suppress colony formation, induce apoptosis, and inhibit metastasis of cancer cells. W4022 effectively curtails the catalytic activities of G9a and NSD2 within cells and demonstrates significant antitumor efficacy in PANC-1 xenograft models.

Guadecitabine sodium is a inhibitor of second-generation DNA methyltransferases (DNMT) .

5-Aza-4'-thio-2'-deoxycytidine (5-Aza-T-dCyd), a sulfur-containing deoxy-cytidine analog, serves as an orally active inhibitor of DNA methyltransferase I (DNMT1). It exhibits potential antitumor effects and DNA hypomethylating properties [1].

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.

GSK3735967 is a selective, reversible, non-nucleoside inhibitor targeting DNMT1, demonstrating an IC50 value of 40 nM. It features a planar dicyanopyridine core designed to specifically interact with DNMT1-bound hemimethylated CpG dinucleotides. Additionally, GSK3735967 possesses three binding sites, with one uniquely capable of binding to histone H4K20me3 [1] [2].

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.

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.

(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.

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

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

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

PNMT-IN-1 (inhibitor 4) is a selective second generation inhibitor [1] of phenylethanolamine N-methyltransferase (PNMT), exhibiting a Ki value of 1.2 nM and an IC50 value of 81 nM. Additionally, it disrupts the activity of DNMT1 and DNMT3b, with IC50 values of 61 μM and 17 μM, respectively, and antagonizes the action of epinephrine.

CM-579 trihydrochloride, a first-in-class reversible, dual inhibitor of G9a and DNMT, exhibits potent in vitro cellular activity across a broad spectrum of cancer cells. It demonstrates inhibition with IC50 values of 16 nM for G9a and 32 nM for DNMT, respectively.