RWJ-56110 

RWJ-56110 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 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 (HY-108566). RWJ-56110 inhibits angiogenesis and blocks the formation of new vessels in vivo. RWJ-56110 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 (HY-108566)^[1].
RWJ-56110 is fully inhibits thrombin-induced RASMC proliferation with an IC₅₀ value of 3.5 μM. RWJ-56110 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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

790.73

C₄₁H₄₃Cl₂F₂N₇O₃

252889-88-6

O=C(N[C@H](C(NCC1=CC=CC=C1)=O)CCN)[C@@H](NC(NC2=CC3=C(C=C2)C(CN4CCCC4)=CN3CC5=C(Cl)C=CC=C5Cl)=O)CC6=CC=C(F)C(F)=C6

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Please store the product under the recommended conditions in the Certificate of Analysis.

• [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.  [Content Brief]

  [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.  [Content Brief]