Activators & Inhibitors

Sildenafil citrate, also known as Revatio, acts by inhibiting cGMP specific phosphodiesterase type 5 (PDE5). The molecular structure of sildenafil is similar to that of cGMP and acts as a competitive binding agent of PDE5.

Sitagliptin, also known as MK-0431 and Januvia, is a Dipeptidyl Peptidase IV Inhibitor.

Azacitidine is also known as Vidaza, 5-azacytidine, Mylosar, and Ladakamycin. Azacitidine and its deoxy derivative, decitabine (5-aza-2'deoxycytidine), are used in the treatment of myelodysplastic syndrome. The azacytidine in the DNA forms a stable complex with DNA methyltransferase enzymes, preventing DNMT activity and resulting in hypomethylation of cellular DNA. Likewise, the incorporation of azacytidine into RNA leads to the dissembly of polyribosomes, defective methylation and inhibition of protein production with subsequent cytotoxicity.

Tubastatin A is a potent HDAC6 inhibitor. It demonstrates over 1,000-fold selectivity against all other HDAC isoforms (IC50 >16 µM), excluding HDAC8 (IC50 = 0.9 µM). Tubastatin A induces a-tubulin hyperacetylation at 2.5 µM in primary cortical neuron cultures. In a model of oxidative stress induced by glutathione depletion, it displays dose-dependent neuronal protection of primary cortical neuron cultures at 5-10 µM.

Mocetinostat (MGCD0103) is an HDAC inhibitor. It was shown to induce hyperacetylation of histones resulting in cancer cell selective apoptosis, and cause cell cycle blockade in various human cancer cell lines in a dose-dependent manner. Mocetinostat inhibites growth of human tumor xenografts in nude mice in a dose-dependent manner and its antitumor activity correlates with induction of histone acetylation in tumors.

RVX-028, also known as RVX-000222, is a potent BET bromodomain inhibitor. It preferentially binds to the second bromodomain on BET proteins. It also stimulates apolipoprotein (APO) AI gene expression, which increases apoA-I and HDL-C in vitro. In vivo, RVX-208 enhances cholesterol efflux via different pathways and significantly increases serum apoA-I and HDL-C in monkeys.

Scriptaid, also known as GCK 1026, is a histone deacetylase inhibitor with optimal concentration of 6-8 µM in a cell based assay. Scriptaid is exhibits lower toxicity than trichostatin A. Scriptaid inhibits tumor growth in vitro and in vivo. It also induces cell cycle arrest in colon cancer cells in culture.

Oxamflatin is a potent inhibitor of histone deacetylases. It has the ability to alter expression of genes involved in cell morphology, motility, apoptosis and cell cycle control, reducing the proliferation of cancer cells.

Chidamide is a histone deacetylase inhibitor which increases Histone H3 acetylation levels in LoVo and HT29 colon cancer cells at low concentrations (4 µM). Chidamide affects the activation of oncogenic signaling kinases by dose-dependently reducing phosphorylated Akt, mTOR, p70S6K, Raf and Erk 1/2 protein expression in colon cancer cells. Chidamide also dose-dependently upregulates p21 protein expression, down-regulates CDK4, and induces cell cycle arrest at the G0/G1 phase.