HPGDS inhibitor 3 is an orally bioactive and potent inhibitor of peripherally restricted hematopoietic prostaglandin D synthase (H-PGDS) with IC50 of 9.4 nM and EC50 of 42 nM. HPGDS inhibitor 3 has good selectivity, good pharmacokinetic parameters in mice, rats and dogs, and no central nervous system toxicity. HPGDS inhibitor 3 has anti~inflammatory activity.

Physicochemical Properties

Molecular Formula	C21H27N3O2
Molecular Weight	353.457985162735
Exact Mass	353.21
CAS #	2255311-93-2
PubChem CID	137362953
Appearance	Typically exists as solid at room temperature
LogP	2.8
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	4
Heavy Atom Count	26
Complexity	511
Defined Atom Stereocenter Count	0
InChi Key	VEKOTFOGNGVLSE-UHFFFAOYSA-N
InChi Code	InChI=1S/C21H27N3O2/c1-21(2,26)16-6-8-17(9-7-16)23-20(25)15-11-14-5-10-18(13-3-4-13)24-19(14)22-12-15/h5,10-13,16-17,26H,3-4,6-9H2,1-2H3,(H,23,25)
Chemical Name	7-cyclopropyl-N-[4-(2-hydroxypropan-2-yl)cyclohexyl]-1,8-naphthyridine-3-carboxamide
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 Vivo	In mice, rats, and dogs, HPGDS Inhibitor 3 (Compound 1y) (1-3 mg/kg; PO and IV; single) has very low brain exposure bioavailability, a similar steady-state volume of distribution, a longer terminal half-life, and a lower IV clearance [1]. In addition to inhibiting LPS-induced increases in PGD2 in plasma and skeletal muscle in a dose-dependent manner, HPGDS inhibitor 3 (0.003-1 mg/kg; oral; single dose) attenuated PGD2 release to baseline levels [1]. HPGDS Inhibitor 3 (PO; single; 0.003–1 mg/kg) [1]. The HPGDS inhibitor 3 (1, 3 and 10 mg/kg; oral; once daily for 16 days) sped up the time it took for the injured limb's muscle to fully recover functionally and greatly improved it [1]. Rats responded well to HPGDS inhibitor 3 (10, 30, and 100 mg/kg; orally; once daily for 7 or 4 days) at 30 mg/kg/day, but not well to 100 mg/kg/day; dogs responded well to 30 mg/kg/day but not to 75 mg/kg/day [1]. HPGDS inhibitor 3's pharmacokinetic characteristics in rats, mice, and dogs [1]. 2.9 5.1 6.2 CL (mL/min/kg) 9.0 4.5 1.9 Vss (L/kg) 1.6 1.6 1.0 F (%) 71 100 92 Brain-blood ratio 0.06; Mouse IV, 1 mg/kg PO, 3 mg/kg Rat IV, 0.4 mg/kg PO, 2.4 mg/kg Dog IV, 0.5 mg/kg PO, 1 mg/kg T1/2 (h)
Animal Protocol	Animal/Disease Models: Male C57BL/6J mice (mouse mast cell degranulation model of inflammation) [1] Doses: 0.003, 0.01, 0.03, 0.1, 0.3 and 1.0 mg/kg Route of Administration: po (po (oral gavage)) Single (1 hour after anesthesia, intraperitoneal (ip) injection of 0.2 mL PBS or 48/80 (0.75 mg/mL)) Experimental Results: PGD2 release is attenuated to baseline levels in a dose-dependent manner with an ED50 of 0.009 mg/kg (blood EC50 = 3.4 nM) in this acute inflammation model. Animal/Disease Models: Male C57BL6/N mice (12 weeks, n=6) [1] Doses: 0.003, 0.01, 0.03, 0.1, 0.3 and 1.0 mg/kg Route of Administration: PO; single dose (intraperitoneal (ip) injection after 1 hour) PBS or 20ng/kg LPS) Experimental Results: Inhibited LPS-induced increases in PGD2 in plasma and skeletal muscle in a dose-dependent manner. Animal/Disease Models: Male C57Bl/6 mice (10-12 weeks, n=7-8; chronic eccentric contraction-induced muscle injury model) [1] Doses: 1, 3 and 10 mg/kg Route of Administration: po (po (oral gavage)) every one time/day for 16 days. Experimental Results: It Dramatically enhanced the functional recovery of the injured
References	[1]. The exploration of aza-quinolines as hematopoietic prostaglandin D synthase (H-PGDS) inhibitors with low brain exposure. Bioorg Med Chem. 2020;28(23):115791.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.8292 mL	14.1459 mL	28.2917 mL
	5 mM	0.5658 mL	2.8292 mL	5.6583 mL
	10 mM	0.2829 mL	1.4146 mL	2.8292 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.