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Substituted indoles as selective protease activated receptor 4 (PAR-4) antagonists: Discovery and SAR of ML354.
TLDR
Using a novel PAC-1 fluorescent αIIbβ3 activation assay this probe molecule antagonist was found to have an IC50 of 140nM for PAR-4 with 71-fold selectivity versus PAR-1 (PAR-1IC50=10μM).
Protease-Activated Receptor (PAR) 1 and PAR4 Differentially Regulate Factor V Expression from Human Platelets
With the recent interest of protease-activated receptors (PAR) 1 and PAR4 as possible targets for the treatment of thrombotic disorders, we compared the efficacy of protease-activated receptor (PAR)1
Synthesis of Indole Derived Protease-Activated Receptor 4 Antagonists and Characterization in Human Platelets
TLDR
Screening and subsequent structure activity relationship analysis yielded several selective PAR4 antagonists as well as possible new scaffolds for future antagonist development.
Development of a Series of (1-Benzyl-3-(6-methoxypyrimidin-3-yl)-5-(trifluoromethoxy)-1H-indol-2-yl)methanols as Selective Protease Activated Receptor 4 (PAR4) Antagonists with in Vivo Utility and
TLDR
A series of highly selective PAR4 antagonists with nanomolar potency and selectivity versus PAR1, derived from the indole-based 3.5-Molecule, maintained an overall favorable in vitro DMPK profile, encouraging rat/mouse in vivo pharmacokinetics (PK) and activity against γ-thrombin.
A Novel and Selective PAR4 Antagonist: ML354
Reactivity of the C2'-oxidized abasic lesion and its relevance to interactions with type I base excision repair enzymes.
TLDR
The inability of endonuclease III to cleave the lesion is due to the absence of appropriately positioned functional groups to take advantage of formation of the covalent intermediate, leaving open the possibility that the C2-AP lesion may be a substrate for other Type I repair enzymes.
Protease-Activated Receptor ( PAR ) 1 and PAR 4 Differentially Regulate Factor V Expression from Human Platelets s
With the recent interest of protease-activated receptors (PAR) 1 and PAR4 as possible targets for the treatment of thrombotic disorders, we compared the efficacy of protease-activated receptor (PAR)1
Figure 5, PAR4 and PAR1 CRC for ML354 (VU0099704)
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