DNA Methyltransferase Inhibitor

(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.

SW155246 is a DNA methyltransferase (DNMT1) selective inhibitor with IC₅₀s of 1.2 and 38 μM for hDNMT1 and mDNMT3A, respectively. SW155246 can be used for the research of cancer and other diseases.

6-Thioguanine (Standard) is the analytical standard of 6-Thioguanine. This product is intended for research and analytical applications. 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.

GSK3735967 is an selective, reversible, non-nucleoside inhibitor of DNMT1 with an IC₅₀ value of 40 nM. GSK3735967 contains a planar dicyanopyridine core that can specifically embed DNMT1 bound hemimethylated CpG dinucleotides. GSK3735967 has three binding sites, one of which can bind to histone H4K20me3.

O6BTG-octylglucoside is a potent O⁶-methylguanine-DNAmethyl-transferase (MGMT) inhibitor, with IC₅₀s of 32 nM in vitro (cell extracts) and 10 nM in HeLa S3 cells.

RSC133 is a dual inhibitor of DNA methyltransferase 1 and histone deacetylase 1 inhibitor. RSC133 promotes cell proliferation, up-regulates H₃K₉ histone acetylation, down-regulates p53, p21, p16/INK4A, and ablates pro-senescence phenotypes.

Levetiracetam (Standard) is the analytical standard of Levetiracetam. This product is intended for research and analytical applications. 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.

CBHcy is an inhibitor for betaine-homocysteine S-methyltransferase (BGMT), with an IC₅₀ of 0.09 μM. CBHcy upregulates the plasma total homocysteine and causes transient hyperhomocysteinemia in mice model.

Benzyl selenocyanate is a chemopreventive agent for various chemically induced tumors in animal models at both the initiation and postinitiation stages. Benzyl selenocyanate is an inhibitor of DNA (cytosine-5)-methyltransferase (Mtase), with an with an IC₅₀ of 8.4 µM.

AA-CW236 is a MGMT (O6-methylguanine DNA methyltransferase) inhibitor. AA-CW236 targets MGMT active site Cys145 for covalent modification.

(S)-GSK-3685032 is the isomer of GSK-3685032 (HY-139664), and can be used as an experimental control. 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.

Hydralazine-d₅ (hydrochloride) is deuterium-labeled Hydralazine (hydrochloride) (HY-B0464). 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.

DNMT2-IN-2 is a selective DNA methyltransferase 2 (DNMT2) inhibitor with a K_D value of 3.04 μM. DNMT2-IN-2 targets to a cryptic allosteric binding site of DNMT2. DNMT2-IN-2 reduces m₅C levels in MOLM-13 tRNA and synergizes with Doxorubicin (HY-15142A) to impair cell viability. DNMT2-IN-2 can be used for cancer research, such as cervical cancer and leukemia.

Levetiracetam-d6 (ring-d6) can be used as internal standard for the determination of Levetiracetam (HY-B0106) content in whole blood.

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

MC3343, a DNMT inhibitor (EC₅₀ of 5.7 μM) and a strong DNA binder, affects tumor proliferation by blocking OS cells in G1 or G2/M phases and induces osteoblastic differentiation through the specific re-expression of genes regulating this physiological process.

Panduratin A is an orally active natural compound with multiple pharmacological activities. By specifically inhibiting the NF-κB signaling pathway, Panduratin A exerts potent anti-inflammatory and antioxidant effects in intestinal and vascular inflammation models. Panduratin A exerts a definite protective effect against Colistin (HY-113678)-induced nephrotoxicity by alleviating oxidative stress, improving mitochondrial dysfunction and inhibiting cell apoptosis. Panduratin A activates autophagy via an AMPK-dependent pathway and exhibits anti-tuberculosis activity. Panduratin A exerts antiviral effects by inhibiting the methyltransferase (DNA Methyltransferase) of SARS-CoV-2.

TDI-015051 is a highly selective, orally active antiviral agent that targets the coronavirus NSP14 guanine-N7 methyltransferase. TDI-015051 binds to substrates in a non-competitive manner and forms a stable ternary complex, precisely blocking the capping and methylation processes of viral mRNA. TDI-015051 potently inhibits a variety of coronaviruses (including SARS-CoV-2 and MERS). By impairing viral replication and translation and inducing a moderate type I interferon-mediated immune response, it significantly reduces pulmonary viral load and exhibits a synergistic effect with Nirmatrelvir (HY-138687). In addition, TDI-015051 does not inhibit non-coronavirus methyltransferases, and the drug-resistant mutations it induces impair viral fitness, demonstrating excellent antiviral properties and safety. TDI-015051 can be used for research on COVID-19 and the replication mechanism of coronaviruses.The IC₅₀ values of TDI-015051 against SARS-CoV-2, α-hCoV-NL63, α-hCoV-229E, β-hCoV-MERS are 0.15 nM, 1.7 nM, 2.6 nM and 3.6 nM, respectively, and the K_a value against SARS-CoV-2 is 0.061 nM.

6-Methyl-5-azacytidine is a potent DNMT inhibitor.

METTL1-WDR4-IN-1 (Compound 1) TFA is a selective competitive inhibitor of the methyltransferase complex METTL1-WDR4 (IC₅₀=144 μM). METTL1-WDR4-IN-1 TFA inhibits the m⁷G methyltransferase activity of the METTL1-WDR4 complex, blocking the m⁷G modification of PKM mRNA, reducing PKM2 protein expression, disrupting the METTL1/PKM2/H3K9la positive feedback loop, and simultaneously inhibiting PKM2 nuclear translocation-mediated CD155 transcriptional activation. METTL1-WDR4-IN-1 TFA can inhibit tumor cell proliferation, weaken glycolytic metabolism, reverse tumor immune evasion (restoring NK cell and CD8⁺ T cell function), and regulate RNA epigenetic modification and the tumor immune microenvironment. METTL1-WDR4-IN-1 TFA can be used in immunotherapy research for cancers such as colorectal cancer, and is particularly suitable for use in combination with PKM2 inhibitors to enhance anti-tumor treatment efficacy.