ML-9 is a selective inhibitor of MYLK and CaMK that acts by delaying MYLK phosphorylation through binding at or near the ATP binding site. This naphthalenesulfonamide derivative has been shown to inhibit insulin-stimulated 2-deoxyglucose transport (IC50 = 27 μM), PP-1 activation in adipocytes, PKA, Akt1 (PKB) and Rsk (S6 kinase). ML-9 was also observed to disrupt microfilament bundles with accompanying decrease in P32 incorporation in rat astrocytes. Carbachol illicited cationic currents were inhibitied with ML-9 (IC50 = 7.8 uM) in HEK293 cells. ML-9 has also demonstrated to inhibit natural killer cell lytic acitivity by regulating microfilament contraction as well as catecholamine secretion in intact and permeabilized chromaffin cells. In addition, agonist-induced Ca2+ entry into endothelial cells was completely abolished in the presence of ML-9. ML-9 was found to be a new type of vascular relaxant. ML-9 produced the relaxation of vascular strips contracted by high K+. The relaxation induced by this compound was not affected by treatment with adrenergic and cholinergic blocking agents. Thus, the ML-9-induced relaxation is not due to a block of membrane receptor-associated mechanisms; rather it has an effect on more basic and common events in smooth muscle contraction. Moreover, ML-9 inhibited the Ca2+-induced contraction in chemically skinned vascular smooth muscle cells, suggesting that ML-9 is not a “calcium channel blocker.”

1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7) is an inhibitor of cAMP-dependent, cGMP-dependent, and Ca2+-phospholipid-dependent (protein kinase C) protein kinases at roughly equal concentrations. It is widely used to study protein kinase signaling both in vitro and in vivo.

Ingenol is an extremely weak PKC (protein kinase C) activator, with potent anticancer activity. Ingenol derivatives have received constant and multidisciplinary attention on account of their pleiotropic pattern of biological activity. This includes activation of PKC (protein kinase C), tumor-promotion, anticancer, and anti-HIV properties, and the possibility of dissecting co-cancerogenic and clinically useful activities has been demonstrated. Certain ingenol esters show powerful anticancer activity, and a structure-activity relationship model to discriminate between their apoptotic and non-apoptotic properties has been developed.

Ingenol is an extremely weak PKC (protein kinase C) activator, with potent anticancer activity. Ingenol derivatives have received constant and multidisciplinary attention on account of their pleiotropic pattern of biological activity. This includes activation of PKC (protein kinase C), tumor-promotion, anticancer, and anti-HIV properties, and the possibility of dissecting co-cancerogenic and clinically useful activities has been demonstrated. Certain ingenol esters show powerful anticancer activity, and a structure-activity relationship model to discriminate between their apoptotic and non-apoptotic properties has been developed.