Enzyme Modulators

ATP-competitive inhibitor of Met and VEGFR2

Inhibitor of histone deacetylases

Inhibitor of mutant B-rafV600E protein that results in decreased proliferation of cancer cells with this mutation. Treatment of metastatic melanoma in patients harboring the V600E mutation, had improved disease outcome. This antitumor activity is enhanced when combined with MEK inhibitor trametinib.

GSK-126 is a potent inhibitor of histone lysine methyl transferase 2, which is encoded by the enhancer of zeste homolog 2 gene (EZH2). The EZH2 protein regulates cell cycle as it represses the Polycomb-Repressive Complex 2 (PRC2), allowing cells to divide actively. GSK-126 inhibits the EZH2 by targeting the catalytic domain (SET) of the enzyme and therefore blocks the PCR2 repression mechanism, resulting in cell proliferation arrest. The compound has shown therapeutic potential for a variety of cancers.

A reversible and selective inhibitor of thrombin that rapidly binds to the catalytic site directly. Inhibits both soluble and bound forms of thrombin. Used for prophylaxis and treatment of heparin-induced thrombocytopenia type II.

Irreversible ErbB receptor tyrosine kinase inhibitor

Tadalafil analogue; PDE 5 inhibitor

Activator of soluble guanylyl cyclase (sGC) which stimulates cGMP production and is effective in cells under oxidative stress. Ataciguat stimulates the heme-free form of the sGC enzyme via the sGC N-terminus of β1-subunit. Ataciguat can promote vasorelaxation and hypotension by restoring or potentiating the nitric oxide (NO) signalling pathway.

Ranolazine is a group P2 drug that reverses the pathogenic mechanism of myocardial infarction. It is used to treat chronic angina. It decreases myocardial wall tension and improves coronary blood flow. It inhibits the ryanodine receptor, which is responsible for regulating the release of intracellular calcium in cardiac and skeletal muscle cells. Furthermore, it is also effective at preventing atrial fibrillation and has been studied as monotherapy as well as in combination with other medications used to treat irregular heartbeat.

Inhibitor of CPT1 and CPT2 enzymes; inhibitor of mTORC1 kinase; anti-fungal

Potent inhibitor of c-Met catalytic activity. Selective over other tyrosine and serine-threonine kinases (600-fold selectivity). Ability to block constitutive or HGF-stimulated phosphorylation of c-Met demonstrated in vitro. JNJ 38877605 reduces radiation-induced invasion, apoptosis and proliferation of cancer cells in vitro.

Inhibitor of B-Raf kinase mutant