Protease-activated (Thrombin) Family Related Drug Discovery Products
Creative Biolabs has the assays you can rely on for high throughput screening, lead optimization, characterizing and discovering targets, and uncovering the complexity of disease pathways. We can offer membrane protein in vitro assay kits that save valuable laboratory time and is ideal for high throughput screening.
Membrane protein stable cell lines are widely used in many areas of biomedical research. Creative Biolabs can offer membrane protein stable cell lines to stablish in vitro models for High Throughput Screening.
Creative Biolabs offers high-quality, innovative tools to help research groups accelerate membrane protein drug discovery. They can be found by targets. If there is no product that meets your needs, please contact us.
Protease-activated receptors (PARs) belong to the family of GPCRs. Proteases specifically cleave the amino terminal sequence of these receptors, exposing a new N-terminal region that functions as a tethered ligand. This ligand then binds intramolecularly to activate the receptor. Although they are found everywhere in the body, the neurological system, vascular, immunological, and intestinal epithelial cells express PARs most frequently. As a result, a number of vital biological processes involved in physiology and illness are controlled by their activations.
Fig.1. Mechanisms of protease-activated receptors activation.1,2
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Protease-Activated Receptors (thrombin) GPCR Assays 
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Overview of Protease-activated (Thrombin) Family
- F2R (PAR1)
By producing RNA from thrombin-responsive cells from humans and hamsters in Xenopus oocytes, the gene for PAR1 was successfully cloned. Clones that encoded a 425 residue protein with 7 typical hydrophobic GPCR domains were discovered. Human PAR1's inferred sequence included an amino-terminal signal sequence, a 75-residue extracellular amino-terminal domain, and a putative thrombin cleavage site in the amino-tail.
- F2RL1 (PAR2)
Using degenerate primers targeting the second and sixth transmembrane domains of the bovine neurokinin 2 receptor, PAR2 was discovered by screening a mouse genomic library. A 395 residue protein with typical GPCR properties and ~30% amino acid identity to human PAR1 was identified to be encoded by a clone. A potential trypsin cleavage site was present at the amino terminus of 46 residues that was extracellular.
- F2RL2 (PAR3)
The discovery that platelets from PAR1-deficient mice responded to thrombin whereas fibroblasts did not suggested the existence of additional receptors for thrombin. In order to filter RNA from rat platelets, PAR3 was subsequently cloned using degenerate primers to conserved regions of PAR1 and PAR2. After being cloned in both human and murine forms, it was discovered that human PAR3 has ~28% of its sequence homology with human PAR1 and PAR2. Similar to PAR1 and PAR2, PAR3 is a conventional GPCR with an extracellular amino terminus thrombin cleavage site.
- F2RL3 (PAR4)
Human PAR4 is a 385-amino acid protein. It may be cleaved by thrombin and trypsin at its extracellular amino-terminal domain. Although PAR4 and the other human PARs share 33% of their amino- and carboxy-terminal domains, there are some noticeable distinctions.
Protease-activated (Thrombin) Family Drug Discovery
It has been established that PARs have a significant role in the control of the physiological functions of the intestine as well as the two major illnesses that affect the organ, inflammatory bowel disorders and colorectal cancer. As a result, the creation of therapeutic drugs is attracted to these G-protein coupled receptors. Though effective PAR antagonist development is still in its early stages, attempts to develop selective receptor inhibitors are now prioritized over targeting their ligands.
References
- Sébert, Morgane, et al. "Protease-activated receptors in the intestine: focus on inflammation and cancer." Frontiers in Endocrinology 10 (2019): 717.
- Distributed under Open Access License CC BY 4.0. The original image was modified by extracting and using part a&b and the title was changed to " Mechanisms of protease-activated receptors activation.".
