Activators & Inhibitors

Activity: DNA hypomethylation agent . Function/Pharmacology: Specific inhibitor of DNA methyltransferase1. Incorporates into DNA and covalently reacts with and inhibits DNA methyltransferases. Induces demethylation and reactivation of silenced genes2. Increases stem cell reprogramming efficiency3. Induces cardiac differentiation of human mesenchymal stem cells by activating ERK4. Induces apoptosis in multiple myeloma cells via ATR-mediated DNA double strand breaks5. Cell permeable. Chemical Name: 4-Amino-1-ß-D-ribofuranosyl-1,3,5-triazin-2(1H)-one

Activity: DNA synthesis and transcription disruptor . Function/Pharmacology: A nucleoside analog that interferes with DNA synthesis and transcription, particularly in tumor cells.1,2 It Cellular enzymes convert it to its nucleotide form, Ara-CTP, which disrupts DNA and RNA synthesis when polymerases attempt to incorporate it.3,4 For the same reasons, it is also employed as an antiviral.5 It inhibits proliferation of a variety of leukemic cell lines (IC50s 16-72 nM), but is used primarily against acute myeloid leukemia (AML).6,7 Chemical Name: 4-Amino-1-β-D-arabinofuranosyl-2(1H)-pyrimidinone

Activity: Thymidylate synthase inhibitor . Function/Pharmacology: 5-Fluorouracil (5-FU) is a clinically useful anticancer agent that acts via irreversible inhibition of thymidylate synthase. The active metabolites of 5-FU are 5-Fluorodeoxyuridylate (5-FdUMP), 5-Fluorodeoxyuridine triphosphate (5-FdUTP) and 5-Fluorouridine triphosphate (5-FUTP). The primary cytotoxic effect of 5-FU is believed to be inhibition of thymidylate synthase by 5-FdUMP. Secondary effects include incorporation of 5-FdUTP into DNA resulting in DNA strand breaks and incorporation of 5-FUTP into RNA causing abnormal RNA processing.1 Chemical Name: 5-Fluoro-1H,3H-pyrimidine-2,4-dione

Activity: Proapoptotic antiproliferative agent . Function/Pharmacology: Inhibitor of ribozyme self-cleavage in mammalian cells.1 Induces apoptosis in HCT-116 colorectal carcinoma cells causing diverse gene expression patterns suggesting that mechanisms besides global inhibition of RNA synthesis and processing contribute to 5-fluorouridine cytotoxicity.2 Cell permeable and active in vivo. Chemical Name: 1-(β-D-Ribofuranosyl)-5-fluorouracil

Activity: Antiviral guanosine ribonucleoside analog . Function/Pharmacology: Ribavirin is a clinically useful antiviral medication for Hepatitis C, viral hemorrhagic fevers and other RNA and DNA viruses. The exact mechanism of its antiviral activity is uncertain. Various proposals include inhibition of viral polymerase1, RNA mutagenesis2, and inosine monophosphate dehydrogenase (IMPDH) inhibition3. Chemical Name: 1-(β-D-Ribofuranosyl)-1H-1,2,4-triazole-3-carboxamide

Activity: Anticancer agent / downregulates DNMT1 . Function/Pharmacology: After incorporation into DNA, it disrupts cytosine methylation by DNA methyltransferases in vitro and acts as a DNA demethylating agent in vivo.1 It reactivates epigenetically silenced genes in acute lymphoblastic leukemia cells by facilitating proteasome-mediated degradation of DNA methyltransferase (DNMT1).2 Incorporates into DNA and induces double strand breaks which destabilize DNA structure resulting in cytotoxicity.3 Selectively kills BRCA2-defective tumors and overcomes PARP inhibitor resistance in a xenograft model.4 Anticancer and immunosuppressive activity. Chemical Name: 2-Amino-6-mercaptopurine

Activity: Thymidylate synthase inhibitor; Anti-cancer agent . Function/Pharmacology: An analog of thymidine which inhibits thymidylate synthase possesses antiviral and anticancer activity.1,2 After phosphorylation by thymidine kinase, it is incorporated into DNA where it induces DNA-damage and interferes with repair enzymes.3 Enhances frame shift insertion and deletion in CRISPR genome editing in pluripotent stem cells.4 Chemical Name: 2’-Deoxy-5-trifluoromethyluridine

Activity: Aminopeptidase inhibitor . Function/Pharmacology: Inhibits leucine aminopeptidase and aminopeptidases B and N. Inhibits leukotriene A4 hydrolase. Displays immunostimulant activity via activation of macrophages and T lymphocytes. Displays antitumor activity. Chemical Name: [(2S,3R)-3-Amino-2-hydroxy-4-phenylbutanoyl]-L-leucine HCl

Activity: Autophagy inducer . Function/Pharmacology: Induces autophagy via an mTOR-independent pathway. Enhances clearance of β-amyloid protein in cell lines and primary neuronal culture models.1-3 May be a useful lead compound for the development of new therapeutics for neurodegenerative diseases.4 Induces the release of articular cartilage vesicles from healthy articular chondrocytes in a dose- and time-dependent manner.5 Promotes reprogramming of fibroblasts to neural stem-like cells.6 Cell permeable.. Chemical Name: 6-Bromo-4-allylaminoquinazoline