RWJ-56110 dihydrochloride is a potent, selective, peptide-mimetic inhibitor of PAR-1 activation and internalization (binding IC50=0.44 uM) and shows no effect on PAR-2, PAR-3, or PAR-4. RWJ-56110 dihydrochloride inhibits the aggregation of human platelets induced by both SFLLRN-NH2 (IC50=0.16 μM) and thrombin (IC50=0.34 μM), quite selective relative to U46619 . RWJ-56110 dihydrochloride blocks angiogenesis and blocks the formation of new vessels in vivo. RWJ-56110 dihydrochloride induces cell apoptosis[1][2]. Proteinase-activated receptors (PARs) are a family of G protein-coupled receptors activated by the proteolytic cleavage of their N-terminal extracellular domain, exposing a new amino terminal sequence that functions as a tethered ligand to activate the receptors.RWJ56110 inhibits the aggregation of human platelets induced by both SFLLRN-NH2 (IC50=0.16 μM) and thrombin (IC50=0.34 μM) while being quite selective relative to collagen and the thromboxane mimetic U46619 [1].RWJ-56110 dihydrochloride is fully inhibits thrombin-induced RASMC proliferation with an IC50 value of 3.5 μM. RWJ-56110 dihydrochloride shows blockade of thrombin's action with RASMC calcium mobilization (IC50=0.12 μM), as well as with HMVEC (IC50=0.13 μM) and HASMC calcium mobilization (IC50=0.17 μM)[1].RWJ56110 (0.1-10 μM; 24-96 hours) inhibits endothelial cell growth dose-dependently, with half-maximal inhibitory concentration of RWJ56110 is approximately 10 μM[2].RWJ56110 (0.1-10 μM; 6 hours) inhibits DNA synthesis of endothelial cells in a thymidine incorporation assays. Endothelial cells are in fast-growing state (50-60% confluence), RWJ56110 inhibits cell DNA synthesis in a dose-dependent manner, but when cells that are in the quiescent state (100% confluent), the inhibitory effect of PAR-1 antagonists is much less pronounced[2].RWJ56110 (0.1-10 μM; pretreatment for 15 min) inhibits thrombin-induced Erk1 2 activation in a concentration-dependent manner. However, when endothelial cells are stimulated by FBS (final concentration 4%), it reduces partially the activated levels of Erk1 2[2].RWJ56110 (30 μM; 24 hours) has an inhibitory effect on endothelial cell cycle progression. It reduces the percentage of cells in the S phase, while alterations in the percentages of G1 and G2 M cells are less pronounced[2]. Western Blot Analysis[2] Cell Line: Endothelial cells [1]. Andrade-Gordon, et al.Design, synthesis, and biological characterization of a peptide-mimetic antagonist for a tethered-ligand receptor. oc Natl Acad Sci U S A. 1999 Oct 26;96(22):12257-62. [2]. Panagiota Zania, et al. Blockade of angiogenesis by small molecule antagonists to protease-activated receptor-1: association with endothelial cell growth suppression and induction of apoptosis. J Pharmacol Exp Ther. 2006 Jul;318(1):246-54.
The leguminous shrub,Leucaena leucocephala(Leucaena) is wide‐spread in tropical and subtropical agricultural systems and provides a ready source of protein for livestock. However, the presence of mimosine, a non‐protein, amino acid comprising about 12% of the dry matter in growing tips ofLeucaena, is toxic to animals. Mimosine is degraded rapidly in the rumen to produce 3,4‐dihydroxypyridine (3,4‐DHP) and 2,3‐dihydroxypyridine (2,3‐DHP), both of which remain toxic to animals[1]. 3,4-DHP, as a derivative of the plant amino acid mimosine, is goitrogenic in cattle, sheep, and mice. In contrast to established antithyroid compounds, such as methimazole (MMI) and propylthiouracil (PTU), 3,4-DHP has no SH-group. 3,4-DHP with various concentrations inhibited incorporation of125I into protein in human thyroid slices. It also suppressed the activation of lymphocytes by PHA (phytohaemagglutinin) and PWM (pokeweed mitogen). Suppression with 3,4-DHP was seen at 100 and 1000 μmol L (P< 0.001 vs both PHA and PWM). Those, together with a very low murine bone marrow toxicity, probably related to the absence of an SH-group, make 3,4-DHP a potential antithyroid drug[2].
GPI-15427 is a potent PARP-1 inhibitor capable of crossing the blood-brain barrier, which can significantly increased the antitumor activity of the methylating agent TMZ against malignant melanoma, glioblastoma multiforme, or lymphoma growing at the CNS site. GPI-15427 acts as a potent inhibitor of the enzyme, being capable of inhibiting the activity of purified PARP-1 at nanomolar concentrations. GPI-15427 induced significant sensitization to radiotherapy, representing a promising new treatment in the management of HNSCC.
PD-128763 is a selective inhibitor of poly(ADP-ribose) polymerase. PD-128763 has an IC50 value against the purified enzyme approximately 50X lower than 3-aminobenzamide (3-AB), a widely used specific inhibitor of the enzyme. Exposure of exponentially growing cells to a noncytotoxic concentration (0.5 mM) of PD 128763 for 2 h immediately following X irradiation increased their radiation sensitivity, modifying both the shoulder and the slope of the survival curve. When recovery from sublethal damage and potentially lethal damage was examined in exponential and plateau-phase cells, respectively, postirradiation incubation with 0.5 mM PD 128763 was found not only to inhibit both these processes fully, but also to enhance further the level of radiation-induced cell killing. This is in contrast to the slight effect seen with the less potent inhibitor, 3-AB. The results presented suggest that the mechanism of radiosensitization by PD 128763 is related to the potent inhibition of pol......
9(Z),11(E),13(Z)-Octadecatrienoic acid methyl ester, an isomer of 9(Z),11(E),13(E)-octadecatrienoic acid methyl ester and the methyl ester derivative of 9(Z),11(E),13(Z)-octadecatrienoic acid, serves as a standard for quantifying 9(Z),11(E),13(Z)-octadecatrienoic acid in wild growing pomegranate (P. granatum) seed oil [Matreya, LLC. Catalog No. 1240].
Prehelminthosporol is a phytotoxin, it may play an important role in pathogenesis by killing or weakening plant cells in advance of the growing hyphae and facilitating nutrient uptake and further growth of the fungus in plant tissue.
Quinupristin is a streptogramin antibiotic. Streptogramins, a class of antibiotics, is effective in the treatment of vancomycin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus, which are two of the most rapidly growing strains of mul