CXCR2-IN-1 is a novel CNS (central nervous system) penetrant antagonist of CXCR2 with a pIC50 of 9.3. It was discovered by structure-activity relationship exploration of the historical biarylurea series. CXCR2-IN-1 demonstrated good developability potentials, a favorable PK profile, and nanomolar potency. More significantly, it demonstrated effectiveness in a model of cuprizone-induced demyelination when taken orally twice daily, supporting the idea that CXCR2 could be a useful target for therapy in the treatment of demyelinating illnesses like multiple sclerosis.

Physicochemical Properties

Molecular Formula	C₁₉H₂₀CL₂FN₃O₄S
Molecular Weight	476.35
Exact Mass	475.053
CAS #	1873376-49-8
Related CAS #	1873376-49-8
PubChem CID	127020968
Appearance	White to off-white solid powder
Density	1.5±0.1 g/cm3
Boiling Point	538.1±50.0 °C at 760 mmHg
Flash Point	279.2±30.1 °C
Vapour Pressure	0.0±1.5 mmHg at 25°C
Index of Refraction	1.647
LogP	4.64
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	4
Heavy Atom Count	30
Complexity	702
Defined Atom Stereocenter Count	0
SMILES	ClC1C([H])=C([H])C(=C(C=1S(C1([H])C([H])([H])C([H])([H])N(C([H])([H])[H])C([H])([H])C1([H])[H])(=O)=O)O[H])N([H])C(N([H])C1C([H])=C([H])C([H])=C(C=1Cl)F)=O
InChi Key	BJYOBCUGMDKPBM-UHFFFAOYSA-N
InChi Code	InChI=1S/C19H20Cl2FN3O4S/c1-25-9-7-11(8-10-25)30(28,29)18-12(20)5-6-15(17(18)26)24-19(27)23-14-4-2-3-13(22)16(14)21/h2-6,11,26H,7-10H2,1H3,(H2,23,24,27)
Chemical Name	1-(2-chloro-3-fluorophenyl)-3-[4-chloro-2-hydroxy-3-(1-methylpiperidin-4-yl)sulfonylphenyl]urea
Synonyms	CXCR2-IN-1; CXCR2-IN 1; CXCR2 IN-1; CXCR2 IN 1
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

Targets	CXCR2 ( pIC50 = 9.3 )
ln Vitro	In vitro activity: CXCR2-IN-1 (compound 22) exhibits a favorable central nervous system penetration property (Br/Bl>0.45)[1]. CXCR2 has a significant impact on the recruitment and activation of neutrophils at inflammatory sites.
ln Vivo	CXCR2-IN-1 demonstrates effectiveness when administered orally in a cuprizone-induced demyelination model, supporting the idea that CXCR2 could be a useful target for therapy in the treatment of demyelinating conditions like multiple sclerosis[1].
Animal Protocol	Mice: Oral administration of CXCR2-IN-1 at doses of 30 and 100 mg/kg twice daily for nine consecutive days follows mice's five-week feeding of cuprizone, which causes demyelinating lesions in the central nervous system[1].
References	[1]. Discovery of CNS Penetrant CXCR2 Antagonists for the Potential Treatment of CNS Demyelinating Disorders. ACS Med Chem Lett. 2016 Feb 8;7(4):397-402.

Solubility Data

Solubility (In Vitro)

DMSO: ~5.4 mg/mL (~11.3 mM) Water: <1 mg/mL Ethanol: <1 mg/mL

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	2.0993 mL	10.4965 mL	20.9930 mL
	5 mM	0.4199 mL	2.0993 mL	4.1986 mL
	10 mM	0.2099 mL	1.0496 mL	2.0993 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.