DNMT1 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.

5-Azacytidine (Azacitidine; 5-AzaC; Ladakamycin) is a nucleoside analogue of cytidine that specifically inhibits DNA methylation. 5-Azacytidine is incorporated into DNA to covalently trap DNA methyltransferases and contributes to reverse epigenetic changes. 5-Azacytidine induces cell autophagy.

GSK-3484862 is a highly potent non-covalent inhibitor and demethylating agent of DNMT1. GSK-3484862 induces genome-wide DNA demethylation, including the regulatory elements of DNMT3B and the promoter region of TERT, and significantly inhibits cell viability, growth, proliferation and self-renewal. GSK-3484862 blocks the transformation of young AT2 cells, induces apoptosis, and generates transcriptomic features similar to those of senescent cells. GSK-3484862 is widely used in studies related to lung cancer, oral squamous cell carcinoma and lung adenocarcinoma.

C188-9 (TTI-101) is a STAT3 inhibitor with a K_d value of 4.7 nM. C188-9 targets the SH2 domain of STAT3, blocks the processes of STAT3 ligand binding, receptor recruitment, homodimerization and phosphorylation, and regulates STAT3-mediated genes associated with tumorigenesis and radioresistance. C188-9 regulates STAT1-mediated genes related to radioresistance and reduces the activation level of STAT1. C188-9 downregulates the expression of DNMT1, enhances DAC-induced demethylation and re-expression of RASSF1A, and simultaneously potentiates the anti-tumor effect of DAC on pancreatic cancer cells. C188-9 inhibits both anchorage-dependent and anchorage-independent growth of cancer cells, induces Apoptosis, blocks the growth of tumor xenografts, and suppresses muscle atrophy. C188-9 maintains muscle mass, increases body weight and improves grip strength in tumor-bearing mice. C188-9 can be used in research related to head and neck squamous cell carcinoma, pancreatic cancer, sepsis-related skeletal muscle wasting, non-small cell lung cancer, acute myeloid leukemia and cancer cachexia.

RG108 (N-Phthalyl-L-tryptophan) is a non-nucleoside DNA methyltransferases (DNMTs) inhibitor (IC₅₀=115 nM) that blocks the DNMTs active site. RG108 (N-Phthalyl-L-tryptophan) causes demethylation and reactivation of tumor suppressor genes, but it does not affect the methylation of centromeric satellite sequences.

MC3817 free base is a selective DNMT1 inhibitor. MC3817 free base inhibits DNMT1 and DNMT3A/3L with IC₅₀s of 0.044 μM and > 10μM, respectively. MC3817 free base inhibits P53-dependent cancer cell proliferation, induces apoptosis and DNA damage. MC3817 free base elevates cleaved Caspase 3, P53, and γH2AX. MC3817 free base can be used in non-small cell lung cancer, colon cancer, cervical cancer, triple-negative breast cancer and histiocytic lymphoma research.

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.

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.

Hinokitiol is a component of essential oils isolated from Chymacyparis obtusa, reduces Nrf2 expression, and decreases DNMT1 and UHRF1 mRNA and protein expression, with anti-infective, anti-oxidative, and anti-tumor activities.

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.

Guadecitabine sodium (SGI-110 sodium) is a second-generation DNA methyltransferases (DNMT) inhibitor for research of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).

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).

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

5-Aza-4'-thio-2'-deoxycytidine (5-Aza-T-dCyd) is an orally active DNA methyltransferase I (DNMT1) inhibitor. 5-Aza-4'-thio-2'-deoxycytidine, a sulfur-containing deoxy-cytidine analog, has the potential for DNA hypomethylating and has antitumor effects.

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.

DC_517 is a DNA methyltransferase 1 (DNMT1) inhibitor, with an IC₅₀ and a K_d of 1.7 μM and 0.91 μM, respectively.

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

(Rac)-GSK-3484862 (GSK3482364) is a selective, orally active, reversible DNA methyltransferase 1 (DNMT1) inhibitor with an IC₅₀ of 0.4 μM. (Rac)-GSK-3484862 inhibits the methyltransferase activity of DNMT1 independently of DNA incorporation, reduces global DNA methylation levels, and relieves the transcriptional repression of HBG1 and HBG2 genes. (Rac)-GSK-3484862 increases fetal hemoglobin levels and the proportion of red blood cells expressing fetal hemoglobin in erythroid progenitor cells and a transgenic mouse model of sickle cell disease. (Rac)-GSK-3484862 can be used in studies related to sickle cell disease.

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.