DNA Methyltransferase 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.

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.

NV914 is an inhibitor of FTSJ1 (tryptophan tRNA-specific 2'-O-methyltransferase) that inhibits the methyltransferase activity of FTSJ1, induces translational readthrough of premature termination codons, and enables genes carrying nonsense mutations to synthesize full-length proteins. NV914 belongs to translational readthrough-inducing compounds (TRIDs). NV914 exhibits translational readthrough activity against nonsense mutations in in vitro systems, does not induce readthrough of natural termination codons, and restores CFTR protein expression. NV914 shows favorable acute oral tolerance in mice, with low health risks and good safety profiles. NV914 is applicable to research related to cystic fibrosis and Shwachman-Diamond syndrome.

AT-1965 is a selective CMTR2 inhibitor that suppresses methyltransferase activity. AT-1965 triggers the intrinsic antiviral immune response in cancer cells, promotes the infiltration and activation of B cells into tumors, and thereby induces antitumor immune memory to prevent tumor recurrence. AT-1965 can be formulated into lipid nanoparticles to achieve rapid tumor regression. AT-1965 is widely used in studies of immunologically "cold" tumors, triple-negative breast cancer, melanoma, Lewis lung cancer, and other malignancies.

Bobcat339 is a potent and selective cytosine-based inhibitor of TET enzyme, with IC₅₀s of 33 μM and 73 μM for TET1 and TET2, respectively. Bobcat339 is useful to the field of epigenetics and serves as a starting point for new therapeutics that target DNA methylation and gene transcription.

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.

6-Thioguanine (Thioguanine; 2-Amino-6-purinethiol) is an anti-leukemia and immunosuppressant agent, acts as an inhibitor of SARS and MERS coronavirus papain-like proteases (PLpros) and also potently inhibits USP2 activity, with IC₅₀s of 25 μM and 40 μM for Plpros and recombinant human USP2, respectively.

MY-1B is a covalent inhibitor of the RNA Methyltransferase NSUN2 (IC₅₀: 1.3 μM). MY-1B stereoselectively ligands active-site cysteine residues (C271) of NSUN2. MY-1B can stereoselectively and covalently bind to PSME1, disrupting the proteasome regulatory complex and downregulating the presentation of specific MHC-I subtypes.

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.

EGR-1-IN-1 is a EGR-1 inhibitor with an IC₅₀ of 1.86 μM. EGR-1-IN-1 binds to the zinc finger DNA-binding domain of EGR-1 and promotes the dissociation of the EGR-1-DNA complex. EGR-1-IN-1 reduces the mRNA expression levels of EGR-1-regulated inflammatory genes induced by TNFα. EGR-1-IN-1 alleviates atopic dermatitis-like lesions in the ear skin of mice. EGR-1-IN-1 serves as a lead compound for the development of targeted compounds for inflammatory skin diseases. EGR-1-IN-1 can be used in studies related to atopic dermatitis.

Bobcat339 hydrochloride is a potent and selective cytosine-based inhibitor of TET enzyme, with the IC₅₀s of 33 μM and 73 μM for TET1 and TET2, respectively. Bobcat339 hydrochloride is useful to the field of epigenetics and serves as a starting point for new therapeutics that target DNA methylation and gene transcription.

Levetiracetam, an antiepileptic agent, binds the synaptic vesicle protein SV2A. Levetiracetam enhances Temozolomide effect on glioblastoma stem cell proliferation and apoptosis. Levetiracetam modulates HDAC levels ultimately silencing MGMT, thus increasing Temozolomide effectiveness. A chemosensitizer agent.

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.

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.

METTL16-IN-1 is a potent METTL16 inhibitor with an IC₅₀ value of 1.7 μM and a K_d value of 1.35 μM. Mettl16-in-1 inhibits the binding interaction of U6 snRNA deletion and METTL16 MTD with an IC₅₀ value of 2.5 μM. METTL16-IN-1 has antitumor activity.

Hydralazine hydrochloride is an orally active, blood-brain barrier-permeable DNA methyltransferase inhibitor with vasodilatory, arterial smooth muscle relaxant and hypotensive activities. Hydralazine hydrochloride reactivates silenced tumor suppressor genes via mediating DNA demethylation, while exerting neuroprotective and anti-inflammatory properties. Hydralazine hydrochloride inhibits NOS-2 (iNOS) and COX-2, and reduces the production of NO and PGE_E2; meanwhile, Hydralazine hydrochloride scavenges reactive oxygen species and inhibits macrophage activation. Hydralazine hydrochloride alleviates motor dysfunction, neuropathic inflammatory pain, and formalin-induced somatic and emotional pain responses. In addition, Hydralazine hydrochloride directly induces DNA strand breaks and sister chromatid exchange, exhibiting certain mutagenic characteristics. Hydralazine hydrochloride has been widely used in studies on hypertension, various cancers (such as cervical cancer, leukemia), spinal cord injury and the mechanisms of inflammatory pain.