SCH79797

SCH-79797 is a potent and selective PAR1 antagonist. SCH-79797 limits myocardial ischemia/reperfusion injury in rat hearts. SCH 79797 protects against ischemia/reperfusion-induced arrhythmias in the rat hearts. SCH 79797 and its N-methyl analog (SCH 203099) inhibited binding of a high-affinity thrombin receptor-activating peptide ([(3)H]haTRAP, Ala-Phe(p-F)-Arg-ChA-HArg-[(3)H]Tyr-NH(2)) to PAR-1 with IC(50) values of 70 and 45 nM, respectively.

Product information

CAS Number: 245520-69-8

Molecular Weight: 371.48

Formula: C23H25N5

Chemical Name: N3-cyclopropyl-7-{[4-(propan-2-yl)phenyl]methyl}-7H-pyrrolo[3, 2-f]quinazoline-1, 3-diamine

Smiles: CC(C)C1C=CC(CN2C=CC3=C4C(N)=NC(NC5CC5)=NC4=CC=C23)=CC=1

InChiKey: AVXQPEKZIGPIJW-UHFFFAOYSA-N

InChi: InChI=1S/C23H25N5/c1-14(2)16-5-3-15(4-6-16)13-28-12-11-18-20(28)10-9-19-21(18)22(24)27-23(26-19)25-17-7-8-17/h3-6,9-12,14,17H,7-8,13H2,1-2H3,(H3,24,25,26,27)

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: To be determined

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

SCH79797 inhibits high-affinity thrombin receptor-activating peptide ([3H]haTRAP) binding in a competitive manner. SCH79797 inhibits α-thrombin- and haTRAP-induced aggregation of human platelets, but does not inhibit human platelet aggregation induced by the tethered ligand agonist for protease-activated receptor-4 (PAR-4), γ-thrombin, ADP, or collagen. Thrombin produces transient increases in cytosolic free Ca2+ concentration ([Ca2+]i) in hCASMC. SCH79797 effectively inhibits this increase in [Ca2+]i. SCH79797 completely inhibits Thrombin- and TK-stimulated [3H]thymidine incorporation. SCH79797 is able to interfere with the growth of several human and mouse cell lines, in a concentration-dependent manner. The ED50 for growth inhibition iss 75 nM, 81 nM and 116 nM for NIH 3T3, HEK 293 and A375 cells, respectively. In NIH 3T3 cells, SCH79797 inhibits serum-stimulated activation of p44/p42 mitogen-activated protein kinases (MAPK) at low concentrations and induces apoptosis at higher concentrations.

In Vivo:

SCH79797 (2.5-250 μg/kg; intravenous injection; male Sprague Dawley rats) treatment immediately before or during ischemia reduces myocardial necrosis following I/R in the intact rat heart in two rat models of myocardial ischemia/reperfusion (I/R) injury. This response is dose-dependent with the optimal dose being 25 μg/kg.

References:

1. Yang H, Li T, Wei J, Zhang H, He S. Induction of tumor necrosis factor (TNF) release from subtypes of T cells by agonists of proteinase activated receptors. Mediators Inflamm. 2013;2013:165453. doi: 10.1155/2013/165453. Epub 2013 Dec 16. PubMed PMID: 24453410; PubMed Central PMCID: PMC3876890.
2. Gong JH, Cho IH, Shin D, Han SY, Park SH, Kang YH. Inhibition of airway epithelial-to-mesenchymal transition and fibrosis by kaempferol in endotoxin-induced epithelial cells and ovalbumin-sensitized mice. Lab Invest. 2014 Mar;94(3):297-308. doi: 10.1038/labinvest.2013.137. Epub 2013 Dec 30. PubMed PMID: 24378645.

Products are for research use only. Not for human use.