SKF-86002 di-HCl is an orally bioactive p38 MAPK inhibitor (antagonist) with anti-inflammatory and anti-arthritic activities and may be utilized in pain relief research. SKF-86002 di-HCl inhibits lipopolysaccharide (LPS)-stimulated production of IL-1 and TNF-α by human monocytes. SKF-86002 di-HCl inhibits lipoxygenase- and cyclooxygenase-mediated arachidonic acid metabolism.

Physicochemical Properties

Molecular Formula	C16H12FN3S.2CLH
Molecular Weight	370.27
Exact Mass	369.026
CAS #	116339-68-5
Related CAS #	SKF-86002;72873-74-6
PubChem CID	10339107
Appearance	Typically exists as solid at room temperature
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	2
Heavy Atom Count	23
Complexity	355
Defined Atom Stereocenter Count	0
SMILES	Cl.Cl.FC1=CC=C(C2N=C3SCCN3C=2C2=CC=NC=C2)C=C1
InChi Key	GQQCNUNCYVXBTF-UHFFFAOYSA-N
InChi Code	InChI=1S/C16H12FN3S.2ClH/c17-13-3-1-11(2-4-13)14-15(12-5-7-18-8-6-12)20-9-10-21-16(20)19-14;;/h1-8H,9-10H2;2*1H
Chemical Name	6-(4-fluorophenyl)-5-pyridin-4-yl-2,3-dihydroimidazo[2,1-b][1,3]thiazole;dihydrochloride
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	UV irradiation-induced stress activation prevents apoptosis; SKF-86002 dihydrochloride (10 μM; 1 hour)[1]. In undifferentiated HL-60 cells, SKF-86002 dihydrochloride does not prevent UV-induced apoptosis[1]. SKF-86002 dihydrochloride (10 μM; 72 hours) had no effect on CD23 mRNA levels but inhibits IL-4-induced monocyte or U937 cell CD23 surface expression and protein formation[4].
ln Vivo	There is antiarthritic efficacy in SKF-86002 dihydrochloride (10-90 mg/kg; po; daily; for 22 days)[5].
Cell Assay	Western Blot Analysis[4] Cell Types: U937 cells Tested Concentrations: 10 μM Incubation Duration: 72 hrs (hours) Experimental Results: diminished CD23 levels on IL-4-treated U937 cells.
Animal Protocol	Animal/Disease Models: Lewis rats, with adjuvant-induced arthritis (AA)[5] Doses: 10 mg/kg , 30 mg/kg, 90 mg/kg Route of Administration: Oral administration, daily, for 22 days Experimental Results: Dramatically diminished hindleg volumes after injection of adjuvant.
References	[1]. p38 mitogen-activated protein kinase-dependent and -independent intracellular signal transduction pathways leading to apoptosis in human neutrophils. J Biol Chem. 1998 Apr 3;273(14):8389-97. [2]. SK&F 86002: a structurally novel anti-inflammatory agent that inhibits lipoxygenase- and cyclooxygenase-mediated metabolism of arachidonic acid. Biochem Pharmacol. 1987 Oct 15;36(20):3463-70. [3]. A protein kinase involved in the regulation of inflammatory cytokine biosynthesis. Nature. 1994;372(6508):739-746. [4]. Inhibitors of the p38 mitogen-activated kinase modulate IL-4 induction of low affinity IgE receptor (CD23) in human monocytes. J Immunol. 1998 Dec 1;161(11):6005-13. [5]. Pharmacologic characterization of the antiinflammatory properties of a new dual inhibitor of lipoxygenase and cyclooxygenase. Agents Actions. 1987 Feb;20(1-2):113-23.

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	2.7007 mL	13.5037 mL	27.0073 mL
	5 mM	0.5401 mL	2.7007 mL	5.4015 mL
	10 mM	0.2701 mL	1.3504 mL	2.7007 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.