HPGDS Inhibitor I (also known as H-PGDS inhibitor 1) is a novel, orally bioavailable, potent and selective inhibitor of Hematopoietic Prostaglandin D Synthase (HPGDS) with IC50 Value of 0.7 nM. HPGDS Inhibitor I demonstrated equal potency against purified HPGDS from human , rat, dog, and sheep with IC50 in the range of 0.5-2.3 nM. Hematopoietic prostaglandin D synthase (HPGDS) is primarly expressed in mast cells, antigen-presenting cells, and Th-2 cells. HPGDS converts PGH2 into PGD2, a mediator thought to play a pivotal role in airway allergy and inflammatory processes. HPGDS Inhibitor I reduces the antigen-induced response in allergic sheep.

Physicochemical Properties

Molecular Formula	C19H19F4N3O
Molecular Weight	381.37
Exact Mass	381.146
CAS #	1033836-12-2
Related CAS #	1033836-12-2
PubChem CID	24991044
Appearance	White to off-white solid powder
Density	1.3±0.1 g/cm3
Boiling Point	487.2±45.0 °C at 760 mmHg
Flash Point	248.5±28.7 °C
Vapour Pressure	0.0±1.2 mmHg at 25°C
Index of Refraction	1.559
LogP	3.24
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	4
Heavy Atom Count	27
Complexity	494
Defined Atom Stereocenter Count	0
InChi Key	LPUCBGGXXIUBAZ-UHFFFAOYSA-N
InChi Code	InChI=1S/C19H19F4N3O/c20-15-3-1-2-13(10-15)17-5-4-14(11-24-17)18(27)25-16-6-8-26(9-7-16)12-19(21,22)23/h1-5,10-11,16H,6-9,12H2,(H,25,27)
Chemical Name	6-(3-fluorophenyl)-N-[1-(2,2,2-trifluoroethyl)piperidin-4-yl]pyridine-3-carboxamide
Synonyms	HPGDS Inhibitor I; H-PGDS Inhibitor I; Prostaglandin D Synthase (hematopoietic-type) Inhibitor I.
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	With an IC50 of 0.5-2.3 nM, HPGDS inhibitor 1 exhibits equivalent potency against purified HPGDS from humans, rats, dogs, and sheep[1].
ln Vivo	Compound 8, or HPGDS inhibitor 1, has a 76% bioavailability, 4.1-hour half-life in rats, and good PK characteristics[1]. Rats given oral doses of HPGDS inhibitor 1 (compound 8) at doses of 1 mg/kg and 10 mg/kg are sacrificed at different intervals. PGD2 production in the rat spleen is inhibited by oral administration of HPGDS inhibitor 1, and this inhibition is inversely correlated with the plasma concentration of HPGDS inhibitor 1 in a time- and dose-dependent manner[1]. In an in vivo sheep model of asthma, HPGDS inhibitor 1 (compound 8; 1 mg/mL) demonstrates effectiveness[1].
Animal Protocol	1 and 10 mpk Rats and sheep
References	[1]. Discovery of an Oral Potent Selective Inhibitor of Hematopoietic Prostaglandin D Synthase (HPGDS). ACS Med Chem Lett. 2010 Feb 2;1(2):59-63.

Solubility Data

Solubility (In Vitro)

DMSO:10 mM Water:<1 mg/mL Ethanol:

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.56 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 25.0 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	2.6221 mL	13.1106 mL	26.2213 mL
	5 mM	0.5244 mL	2.6221 mL	5.2443 mL
	10 mM	0.2622 mL	1.3111 mL	2.6221 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.