T3729

Ethyl gallate (gallic acid ethyl ester) obviously decreases cell proliferation in MDA-MB-231 and MCF-7 cells in a dose- and time-dependent manner, exhibits cytotoxicity in a dose-dependent manner. Ethyl gallate can inhibit the abilities of invasion of breast cancer in vitro by inhibiting the mRNA levels of MMP-9/MMP-2, phosphorylation of Akt and protein expression of NF-κB and inhibits hydrogen peroxide signaling, may represent an alternative class of vasopressors for use in septic shock. Also, Ethyl gallate suppresses proliferation and invasion in human breast cancer cells by modulating the PI3K/Akt pathway, which may contribute to inhibiting their downstream targets such as NF-κB p-65, Bcl-2/Bax, and mRNA levels of MMP-2 and MMP-9 in breast cancer cells, could be used as potential antioxidants with safe therapeutic application in cancer chemotherapy.

Lyso-globotriaosylceramide is a form of globotriaosylceramide that is lacking the fatty acyl group. It binds to Shiga toxin 1 (Stx1) in the presence of cholesterol and phosphatidylcholine but does not bind Stx2. It also reduces viability and aggregation of human neutrophils induced by phorbol 12-myristate 13-acetate when used at concentrations of 50 and 1 μM, respectively. Lyso-globotriaosylceramide accumulates in the brain, heart, kidney, liver, lung, and spleen in a mouse model of Fabry disease, a lysosomal storage disorder characterized by a deficiency in the enzyme α-galactosidase A. It also accumulates in the urine, kidney, and plasma of patients with Fabry disease. Lyso-globotriaosylceramide levels decrease in response to administration of the α-galactosidase inhibitor 1-deoxygalactonojirimycin in a transgenic mouse model of Fabry disease. Decreases in plasma and urine concentrations of lyso-globotriaosylceramide have been used as a biomarker for efficacy of enzyme replacement therapy (ERT) and other therapies in the treatment of Fabry disease.

TLR4 inhibitor. Inhibits LPS-induced NF-κB activation in HEK293 cells (IC50 = 2.4 μg/mL). Also inhibits LPS-induced cytokine production and procoagulant effects in PBMCs and HUVECs. Prolongs survival in a mouse septic shock model.

GoSlo-SR-5-69 is a potent high-conductance calcium-activated potassium channel (BK channel) agonist, with an EC50 of 251 nM. GoSlo-SR-5-69 significantly shifts the voltage required for half-maximal activation in a negative direction (ΔV1/2 = −104 mV), thereby enhancing channel open probability. Widely used in studies of neuronal excitability, vasodilation, smooth muscle regulation, and ion channel pharmacology, it elucidates BK channel function under physiological and pathological conditions.

TREK1 and TREK2 channel activator (EC50 = 0.76 μM in Rb efflux assay in TREK1-expressing CHO cells). Exhibits selectivity for TREK1/2 over TRAAK, TASK3 and a range of other potassium channels. Hyperpolarizes membrane potential of dorsal root ganglion neurons and depresses neuronal activity in vitro. Loucif et al (2018) GI-530159, a novel, selective, mechanosensitive two-pore-domain potassium (K2P) channel opener, reduces rat dorsal root ganglion neuron excitability. Br.J.Pharmacol. 175 2272 PMID:29150838

Spinacine has been isolated from spinach and the roots of Panax ginseng. This conformationally constrained amino acid is a structural element in certain biologically active compounds as glucagon antagonists and angiotensin II receptor antagonists. Spinacine can be inserted as a His replacement with a locked imidazole moiety for elucidating the role of the lateral heterocycle in the activity of a peptide.

L-Palmitoylcarnitine chloride (Palmitoyl-L-carnitine chloride) is a fatty acid metabolite with antithrombotic properties that protects mice from ischemic stroke by counteracting intracerebral thrombosis in the tMCAO model.L-Palmitoylcarnitine chloride (Palmitoyl-L-carnitine chloride) is a fatty acid metabolite with antithrombotic properties. Palmitoylcarnitine chloride inhibits the Na/K pump in the heart and inhibits FeCl 3-induced arterial thrombosis Attenuates intracerebral thrombosis and inflammation in a mouse model of transient middle cerebral artery occlusion (tMCAO).