AZ8838 is a potent, competitive, allosteric, orally bioactive PAR2 non-peptide small molecule antagonist (inhibitor) with pKi of 6.4 for hPAR2.

Physicochemical Properties

Molecular Formula	C13H15FN2O
Molecular Weight	234.269406557083
Exact Mass	234.116
CAS #	2100285-41-2
Related CAS #	2100285-41-2 (S-isomer);2100283-63-2 (Racemate);2151021-59-7 (R-isomer);
PubChem CID	126961334
Appearance	Off-white to light yellow solid powder
LogP	2.3
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	4
Heavy Atom Count	17
Complexity	240
Defined Atom Stereocenter Count	1
SMILES	FC1C=CC([C@H](C2=NC=CN2)O)=C(C=1)CCC
InChi Key	IDFPQEHZYBXIFO-LBPRGKRZSA-N
InChi Code	InChI=1S/C13H15FN2O/c1-2-3-9-8-10(14)4-5-11(9)12(17)13-15-6-7-16-13/h4-8,12,17H,2-3H2,1H3,(H,15,16)/t12-/m0/s1
Chemical Name	(S)-(4-fluoro-2-propylphenyl)-(1H-imidazol-2-yl)methanol
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
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	AZ8838 is kept in a closed pocket [1]. In Ca2+ assay, AZ8838 is a strong antagonist of SLIGRL-NH2, having a pIC50 of 5.70 ± 0.02[1]. AZ8838 shown efficacy in suppressing IP1 synthesis (pIC50 = 5.84 ± 0.02) [1]. AZ8838 inhibits peptide-induced ERK1/2 phosphorylation (pIC50 = 5.7 ± 0.1) and β-arrestin-2 recruitment (pIC50 = 6.1 ± 0.1) [1].
ln Vivo	A PAR2 agonist-induced rat paw edema model has demonstrated anti-inflammatory effects with AZ8838 (10 mg/kg; oral; 2 hours ago) [1].
Animal Protocol	Animal/Disease Models: Wistar rat, acute edema model induced by PAR2 agonist 2f-LIGRLO-NH2 [1] Doses: 10 mg/kg Route of Administration: Oral administration, once, 2 hrs (hrs (hours)) ago Experimental Results: demonstrated a 60% reduction in foot swelling . Inhibition of 2f-LIGRLO-NH2 induces activated mast cells, inhibition of 2f-LIGRLO-NH2 reduces tryptase-positive (AA1+ve) intact mast cells in the paw, and blocks histamine release.
References	[1]. Protease-activated receptor-2 ligands reveal orthosteric and allosteric mechanisms of receptor inhibition. Commun Biol. 2020 Dec 17;3(1):782. [2]. Structural insight into allosteric modulation of protease-activated receptor 2. Nature. 2017;545(7652):112-115.

Solubility Data

Solubility (In Vitro)

DMSO : ~200 mg/mL (~853.72 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 5 mg/mL (21.34 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 5 mg/mL (21.34 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. Solubility in Formulation 3: ≥ 5 mg/mL (21.34 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	4.2686 mL	21.3429 mL	42.6858 mL
	5 mM	0.8537 mL	4.2686 mL	8.5372 mL
	10 mM	0.4269 mL	2.1343 mL	4.2686 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.