INCB38579 is an orally bioactive, highly brain-penetrating and selective histamine H4 receptor (HH4R) antagonist (hH4R IC50=4.8 nM, mH4R IC50=42 nM, rH4R IC50=32 nM). INCB38579 has anti~inflammatory and anti-pruritic activities.

Physicochemical Properties

Molecular Formula	C25H34N6O
Molecular Weight	434.577064990997
Exact Mass	434.279
CAS #	1246207-65-7
PubChem CID	59496762
Appearance	Off-white to light yellow solid powder
LogP	3.2
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	4
Heavy Atom Count	32
Complexity	632
Defined Atom Stereocenter Count	0
SMILES	C(=O)(N1CCC2=C(C1)C=C(C1C=C(N3CCN(C)CC3)N=C(N)N=1)C=C2)CC1CCCC1
InChi Key	LZOCXAJJOQPLKB-UHFFFAOYSA-N
InChi Code	InChI=1S/C25H34N6O/c1-29-10-12-30(13-11-29)23-16-22(27-25(26)28-23)20-7-6-19-8-9-31(17-21(19)15-20)24(32)14-18-4-2-3-5-18/h6-7,15-16,18H,2-5,8-14,17H2,1H3,(H2,26,27,28)
Chemical Name	1-[7-[2-amino-6-(4-methylpiperazin-1-yl)pyrimidin-4-yl]-3,4-dihydro-1H-isoquinolin-2-yl]-2-cyclopentylethanone
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	Histamine binding to recombinant codont-bearing histamine H4 receptors is inhibited by INCB38579 (0.1 nM-10 μM; 1.5 hours) [1]. The human eosinophil migration produced by histamine is blocked by INCB38579 (0.1 nM-10 μM; 20 min). Human eosinophil movement is inhibited and histamine-induced alterations in cell shape are blocked in a dose-dependent manner by NCB38579 (0-30 nM; 1.5 h) [1].
ln Vivo	INCB38579, a bacteriostatic histamine-mediated anesthetic pruritus treatment (chamber gavage; 100 mg/kg; once) [1]. In this acute model of narcotic pain, mice Formalin-induced pain function and fluorescence adsorption are used to study INCB38579 (chamber gavage; 100 mg/kg; once) [1].
Cell Assay	Cell Viability Assay [1] Cell Types: HEK293 cells Tested Concentrations: 0.1 nM-10 μM Incubation Duration: 1.5 hrs (hours) Experimental Results: Shows IC50 values for human, mouse and rat histamine H4 receptors of 4.8, 42 and 21 nM, respectively. Cell viability assay[1] Cell Types: human monocytes, mouse bone marrow cells and human eosinophils Tested Concentrations: 0.1 nM-10 μM Incubation Duration: 20 minutes Experimental Results: IC50 of human monocytes and mouse bone marrow cells respectively are 13.2 and 77 nM, respectively. The IC50 value of purified human eosinophils was shown to be approximately 20-30 nM. Cell viability assay [1] Cell Types: HEK293 Cell Tested Concentrations: 0-30 nM Incubation Duration: 1.5 hrs (hours) Experimental Results: IC50 values for human, mouse and rat histamine H4 receptors were 4.8, 42 and 21 nM respectively.
Animal Protocol	Animal/Disease Models: Female. Itching caused by histamine in CD-1 mice [1] Doses: 100 mg/kg Route of Administration: po (oral gavage); 100 mg/kg; one-time Experimental Results:Dramatically diminished scratching times (P<0.05). Animal/Disease Models: SD (SD (Sprague-Dawley)) rats injected with carrageenan [1] Doses: 100 mg/kg Route of Administration: po (oral gavage); 100 mg/kg; Experimental Results: Increased paw withdrawal threshold from baseline of 61 g to approx. 100 g, achieving approximately 60% of the maximum possible effect. Animal/Disease Models: Male SD (SD (Sprague-Dawley)) rats and male ICR mice were injected with formalin in the hind paws [1] Doses: 3, 10, 30 and 100 mg/kg Route of Administration: po (oral gavage); 3, 10, 30 and 100 mg/kg; Experimental Results: In the mouse formalin test, 10 to 100 mg/kg in the first phase response and 30 to 100 mg/kg in the second phase response demonstrated significant dose-dependent antidote. pain effect. In the rat formalin test, a dose-dependent and statistically significant phase 1 response was observed at 10 to 100 mg/kg.
References	[1]. INCB38579, a novel and potent histamine H₄ receptor small molecule antagonist with anti-inflammatory pain and anti-pruritic functions. Eur J Pharmacol. 2012 Jan 30;675(1-3):47-56.

Solubility Data

Solubility (In Vitro)

DMSO : ~230 mg/mL (~529.25 mM)

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	2.3011 mL	11.5054 mL	23.0107 mL
	5 mM	0.4602 mL	2.3011 mL	4.6021 mL
	10 mM	0.2301 mL	1.1505 mL	2.3011 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.