Activators & Inhibitors

ABT-888 (Veliparib) is a potent inhibitor of both PARP-1 and PARP-2. In the MX-1 breast xenograft model (BRCA1 deletion and BRCA2 mutation), ABT-888 potentiated cisplatin, carboplatin, and cyclophosphamide, causing regression of established tumors, whereas with comparable doses of cytotoxic agents alone, only modest tumor inhibition was exhibited.

Trichostatin A (TSA) is an antifungal antibiotic with cytostatic and differentiating properties in mammalian cell culture.

EX 527 is a potent and selective SIRT1 class III histone deacetylase enzyme inhibitor. It is Selective inhibitor of SIRT1 that does not class I/II inhibit histone deacetylase (HDAC) or other sirtuin deacetylase family members. EX 527 has been used a powerful tool for studying the relationship between SIRT1 and cell regulation.

Curcumin, also known as diferuloylmethane, natural yellow 3, or C.I. 75300, is the principal curcuminoid of the popular Indian spice turmeric, which is a small molecule, selective HAT inhibitor. It has shown to promote degradation of p300 and inhibits the acetyltransferases activity of purified p300 using either histone H3 or p53 as a substrate.

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.