| Size | Price | |
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| 25mg | ||
| 50mg | ||
| 100mg |
| ln Vitro |
The N-terminal extracellular domain of protease-activated receptors (PARs), a family of G-protein-coupled receptors, is cleaved by proteases to reveal a novel amino-terminal region that functions as a tethering ligand to activate the receptor. RWJ56110 exhibits significant selectivity in inhibiting human platelet aggregation produced by SFLLRN-NH2 (IC50=0.16 μM) and thrombin (IC50=0.34 μM), as compared to collagen and the thromboxane mimic U46619 [1]. At an IC50 of 3.5 μM, RWJ-56110 totally prevents thrombin-induced RASMC growth. Research has demonstrated that RWJ-56110 inhibits thrombin via RASMC calcium mobilization (IC50=0.12 μM), HMVEC (IC50=0.13 μM), and HASMC calcium mobilization (IC50=0.17 μM) [1]. RWJ56110 (0.1–10 μM; 24-96 hours) has a dose-dependent inhibitory effect on endothelial cell proliferation, with a half-maximum inhibitory concentration of about 10 μM [2]. Thymidine incorporation assay results show that RWJ56110 (0.1–10 μM; 6 hours) inhibits endothelial cell DNA synthesis. RWJ56110 suppresses cellular DNA synthesis in a dose-dependent manner in endothelial cells in a rapidly expanding state (50–60% confluence), although the inhibitory effect of PAR-1 antagonists is less noticeable in cells in a resting state (100% confluence). Reference [2]. Erk1/2 activation mediated by thrombin is inhibited in a concentration-dependent manner by RWJ56110 (0.1-10 μM; 15 min pretreatment). Nevertheless, the degree of Erk1/2 activation is somewhat decreased when endothelial cells are stimulated with FBS (final concentration 4%) [2]. The endothelial cell cycle progression is inhibited by RWJ56110 (30 μM; 24 h). The percentage of cells in S phase decreases as a result, while the alterations in the G1/M and G1 cell percentages are less noticeable [2].
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| Cell Assay |
Western Blot Analysis [2]
Cell Types: Endothelial cells Tested Concentrations: 0 μM; 3μM; 1μM; 3μM; 10 μM Incubation Duration: 15 minutes of pretreatment Experimental Results: Result in MAPK activation in endothelial cells. Cell cycle analysis [2] Cell Types: endothelial cells Tested Concentrations: 0 μM; 3μM; 1μM; 3μM; 10 μM Incubation Duration: 15 minutes of pretreatment Experimental Results: diminished number of cells in S phase. |
| References |
[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. |
| Molecular Formula |
C41H43CL2F2N7O3
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|---|---|
| Molecular Weight |
790.74
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| Exact Mass |
789.2773
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| CAS # |
252889-88-6
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| Related CAS # |
RWJ-56110 dihydrochloride;2387505-58-8
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| Appearance |
Typically exists as solids (or liquids in special cases) at room temperature
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| SMILES |
O=C(NCC1=CC=CC=C1)[C@@H](NC([C@@H](NC(NC2=CC3=C(C=C2)C(CN4CCCC4)=CN3CC5=C(Cl)C=CC=C5Cl)=O)CC6=CC=C(F)C(F)=C6)=O)CCN
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| InChi Key |
SWPAWRHBFNDXEU-BCRBLDSWSA-N
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| InChi Code |
InChI=1S/C41H43Cl2F2N7O3/c42-32-9-6-10-33(43)31(32)25-52-24-28(23-51-17-4-5-18-51)30-13-12-29(21-38(30)52)48-41(55)50-37(20-27-11-14-34(44)35(45)19-27)40(54)49-36(15-16-46)39(53)47-22-26-7-2-1-3-8-26/h1-3,6-14,19,21,24,36-37H,4-5,15-18,20,22-23,25,46H2,(H,47,53)(H,49,54)(H2,48,50,55)/t36-,37-/m0/s1
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| Chemical Name |
(2S)-4-amino-2-[[(2S)-2-[[1-[(2,6-dichlorophenyl)methyl]-3-(pyrrolidin-1-ylmethyl)indol-6-yl]carbamoylamino]-3-(3,4-difluorophenyl)propanoyl]amino]-N-(phenylmethyl)butanamide
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| Synonyms |
RWJ 56110 RWJ56110RWJ-56110
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.2646 mL | 6.3232 mL | 12.6464 mL | |
| 5 mM | 0.2529 mL | 1.2646 mL | 2.5293 mL | |
| 10 mM | 0.1265 mL | 0.6323 mL | 1.2646 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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