DNA Methyltransferase Inhibitor

GSK-3484862 GMP is GSK-3484862 (HY-135146) produced by using GMP guidelines. GMP small molecules works appropriately as an auxiliary reagent for cell therapy manufacture. 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.

RU-0415529 is an orally active inhibitor for SARS-CoV-2 nonstructural protein 14 (NSP14) with an IC₅₀ of 356 nM. RU-0415529 binds to the SAH-stabilized cap binding pocket, inhibits viral RNA methylation and the viral replication. RU-0415529 exhibits anti-infectious activity in mouse models.

DNMT/HDAC-IN-2 (Compound Y7) is a DNMT and HDAC inhibitor with IC₅₀ values for DNMT1, HDAC1, and HDAC6 of 365, 0.2, and 8.91 nM respectively. DNMT/HDAC-IN-2 inhibits the proliferation of breast cancer cells. DNMT/HDAC-IN-2 significantly reduces tumor growth in xenografts and transgenic breast cancer mouse models. DNMT/HDAC-IN-2 can be used for the study of breast cancer.

USP7-IN-18 is a naphthalene derivative. USP7-IN-18 is a selective USP7 inhibitor (IC₅₀ : 130.9 nM), with no or very weak inhibition of the other 8 DUBs including USP47. USP7-IN-18 specifically binds to the catalytic domain of USP7, blocking its deubiquitinase activity. USP7-IN-18 causes degradation of the oncogenic proteins MDM2 and DNMT1, and also degrades the novel target PCLAF. USP7-IN-18 activates the p53-p21 pathway. USP7-IN-18 exerts anti-tumor effects in colon cancer animal models and reshapes the tumor immune microenvironment. USP7-IN-18 achieves both direct cytotoxic and immune-synergistic anti-tumor actions.

DNMT2-IN-1 (compound 80) is a potent and selective DNMT2 (DNA methyltransferase 2) inhibitor with an IC₅₀ value of 1.2 μM, and has the potential for mental and metabolic disorders or cancer research.

ZIKV-IN-3 (compound 5a), an andrographolide derivatives, is a potent ZIKV NS5 methyl transferase (MTase) inhibitor with an IC₅₀ value of 18.34 μM. ZIKV-IN-3 inhibits ZIKV replication and infection. ZIKV-IN-3 can be used in research of Zika virus (ZIKV).

(4aS,8aR)-NPD-001 is a potent and allosteric inhibitor of DNMT3A. (4aS,8aR)-NPD-001 inhibits DNMT3A activity by disrupting protein-protein interactions. (4aS,8aR)-NPD-001 induces apoptosis of acute myeloid leukemia (AML) cell lines. (4aS,8aR)-NPD-001 induces differentiation of distinct AML cell lines including cells with mutated DNMT3A R882.

p53 Activator 13 (compound 11) is a 6mA methyltransferase CamA inhibitor and a p53 activator. p53 Activator 13 intercalates into CamA-bound DNA via the minor groove, causing a conformational shift that moves the catalytic domain away from the DNA and elicits DNA damage response via p53 activation. p53 Activator 13 can be utilized in cancer research.

MGMT-IN-1 (Compound 2) is a light-activated MGMT inhibitor. MGMT-IN-1 can effectively enhance the cytotoxicity of Temozolomide (TMZ) (HY-17364) only under light conditions, significantly increasing the DNA damage caused by TMZ. MGMT-IN-1 can be used for the study of chordoma.

ZIKV-IN-2 (compound 3a) is a potent ZIKV NS5 methyl transferase (MTase) inhibitor with an IC₅₀ value of 38.86 μM. ZIKV-IN-2 inhibits ZIKV replication and infection. ZIKV-IN-2 can be used in research of Zika virus (ZIKV).

DNMT3A-IN-4 is a DNMT3A inhibitor with an IC₅₀ of 33.4 μM against human DNMT3A. DNMT3A-IN-4 inhibits the proliferation of colorectal cancer cells and can be used for the research of colorectal cancer.

RG108 (GMP) is RG108 (HY-13642) produced by using GMP guidelines. GMP small molecules works appropriately as an auxiliary reagent for cell therapy manufacture. 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.

DNMT-IN-5 is a stable and efficient DNA methyltransferase (DNMT) inhibitor with high stability and high activity with an IC₅₀ of 0.78 nM. DNMT-IN-5 exhibits sub-micromolar DNMT3A inhibitory activity, upregulates the expression of DNMT-targeted genes, impairs cell proliferation, and triggers a critical cell cycle arrest. DNMT-IN-5 can be used for the study of p53-depleted colorectal cancer.

Hedgehog IN-11 is an orally active Hedgehog inhibitor. Hedgehog IN-11 downregulates the expression of O6-methylguanine-DNA methyltransferase (MGMT) to impair the Temozolomide (TMZ) (HY-17364) resistance by inhibiting the Hedgehog pathway. Hedgehog IN-11 shows improved inhibition of cell migration and invasion, and induced cell apoptosis in TMZ-resistant GBM cell lines. Hedgehog IN-11 is predicted by computer simulation to have good blood-brain barrier penetration. Hedgehog IN-11 can be used for the study of glioblastoma (GBM).

DNMT-IN-1 is a potent DNMT inhibitor with an EC₅₀ value of 3.2 µM. DNMT-IN-1 shows antiproliferative active.

GSK3830052 is a selective DNA methyltransferase 1 (DNMT1) inhibitor. GSK3830052 can be used to study cancer, sickle cell disease, β-thalassemia, and other diseases associated with DNMT1 inhibition.

Dihydro-5-azacytidine acetate (DHAC), the nucleoside analog, is incorporated into DNA and inhibits DNA methylation. Dihydro-5-azacytidine acetate has an antitumor activity.

DNMT-IN-4 (Compound 4d) is a DNMT inhibitor with an IC₅₀ of 5.78 µM. DNMT-IN-4 can induce apoptosis and has anticancer activity.

2′-Deoxy-5-nitrocytidine is a DNA Methyltransferase inhibitor extracted from patent CN108498529A. 2′-Deoxy-5-nitrocytidine can be used for the research of cancer.

Dihydro-5-azacytidine (DHAC), the nucleoside analog, is incorporated into DNA and inhibits DNA methylation. Dihydro-5-azacytidine has an antitumor activity.