SCH79797 diHCl is a potent and specific non-peptidyl protease-activated receptor 1 (PAR1) antagonist. SCH79797 diHCl inhibits/disrupts the binding of high-affinity thrombin receptor activating peptide to PAR1 with IC50 of 70 nM and Ki of 35 nM. SCH79797 diHCl inhibits thrombin-induced platelet aggregation with IC50 of 3 μM. SCH79797 diHCl displays antiproliferation and proapoptotic effects and limits myocardial ischemia/reperfusion injury in rat hearts. SCH79797 diHCl also effectively prevents PAR1 activation in vascular smooth muscle cells, endothelial cells, and astrocytes.

Physicochemical Properties

Molecular Formula	C₂₃H₂₇CL₂N₅
Molecular Weight	444.40
Exact Mass	443.164
CAS #	1216720-69-2
Related CAS #	SCH79797;245520-69-8
PubChem CID	45073452
Appearance	White to yellow solid powder
LogP	7.17
Hydrogen Bond Donor Count	4
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	5
Heavy Atom Count	30
Complexity	527
Defined Atom Stereocenter Count	0
Synonyms	SCH79797 diHCl; SCH-79797 diHCl
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	Thrombin receptor activating peptide ([3H]haTRAP) binding with high affinity is competitively inhibited by SCH79797. ADP, collagen, gamma-thrombin, protease-activated receptor 4 (PAR-4), and alpha-thrombin all cause human platelet aggregation, which is inhibited by SCH79797. Cytosolic free Ca2+ concentration ([Ca2+]i) in hCASMCs is temporarily elevated by thrombin. The accumulation of [Ca2+]i is efficiently inhibited by SCH79797. [3H]Thymidine incorporation increased by TK and thrombin is totally inhibited by SCH79797 [1]. A concentration-dependent effect of SCH79797 is observed on the proliferation of several human and animal cell lines. With regard to NIH 3T3, HEK 293 and A375 cells, the corresponding ED50 values were 75 nM, 81 nM and 116 nM. SCH79797 elicits apoptosis in NIH 3T3 cells at higher doses while at lower concentrations inhibiting serum-stimulated p44/p42 mitogen-activated protein kinase (MAPK) activation [2].
ln Vivo	In two models of myocardial ischemia/reperfusion (I/R) injury, SCH79797 (2.5-250 μg/kg; i.v.; male Sprague Dawley rats) given immediately before or during ischemia reduced intact rats Myocardial necrosis after cardiac I/R. The response is dosage-dependent, with the optimal dose being 25 μg/kg[4].
Animal Protocol	Animal/Disease Models: Male Sprague Dawley rats (8 weeks old) with myocardial I/R injury [4] Doses: 2.5 μg/kg, 10 μg/kg, 25 μg/kg, 50 μg/kg, 100 μg/kg and 250 μg/kg Route of Administration: IV Experimental Results: Myocardial necrosis after I/R was diminished in intact rat hearts before or during ischemia.
References	[1]. Inhibition of cellular action of thrombin by N3-cyclopropyl-7-[[4-(1-methylethyl)phenyl]methyl]-7H-pyrrolo[3, 2-f]quinazoline-1,3-diamine (SCH 79797), a nonpeptide thrombin receptor antagonist. Biochem Pharmacol. 2000 Nov 15;60(10):1425-34. [2]. Protease-activated receptor 1-selective antagonist SCH79797 inhibits cell proliferation and induces apoptosis by a protease-activated receptor 1-independent mechanism. Basic Clin Pharmacol Toxicol. 2007 Jul;101(1):63-9. [3]. A novel therapeutic target in various lung diseases: airway proteases and protease-activated receptors. Pharmacol Ther. 2007 Jul;115(1):70-83. [4]. SCH 79797, a selective PAR1 antagonist, limits myocardial ischemia/reperfusion injury in rat hearts. Basic Res Cardiol. 2007 Jul;102(4):350-8.

Solubility Data

Solubility (In Vitro)

DMSO : ~22 mg/mL (~49.50 mM) Ethanol : ~11 mg/mL (~24.75 mM)

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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.2502 mL	11.2511 mL	22.5023 mL
	5 mM	0.4500 mL	2.2502 mL	4.5005 mL
	10 mM	0.2250 mL	1.1251 mL	2.2502 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.