GSK143 is an orally bioactive, selective inhibitor of spleen tyrosine kinase (SYK) with pIC50 of 7.5. GSK143 inhibits Erk phosphorylation (pErk: pIC50=7.1). GSK143 reduces inflammation and prevents immune cell recruitment in the intestinal muscularis of mice.

Physicochemical Properties

Molecular Formula	C17H22N6O2
Molecular Weight	342.39558
Exact Mass	342.18
CAS #	1240390-27-5
Related CAS #	GSK143 dihydrochloride;2341796-81-2
PubChem CID	46865656
Appearance	Typically exists as solid at room temperature
LogP	2.702
Hydrogen Bond Donor Count	4
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	5
Heavy Atom Count	25
Complexity	443
Defined Atom Stereocenter Count	2
SMILES	CC1=CC=C(NC2=NC(N[C@@H]3CCOC[C@@H]3N)=NC=C2C(N)=O)C=C1
InChi Key	KBPYMFSSFLOJPH-UONOGXRCSA-N
InChi Code	InChI=1S/C17H22N6O2/c1-10-2-4-11(5-3-10)21-16-12(15(19)24)8-20-17(23-16)22-14-6-7-25-9-13(14)18/h2-5,8,13-14H,6-7,9,18H2,1H3,(H2,19,24)(H2,20,21,22,23)/t13-,14+/m0/s1
Chemical Name	2-[[(3R,4R)-3-aminooxan-4-yl]amino]-4-(4-methylanilino)pyrimidine-5-carboxamide
Synonyms	GSK-143 GSK 143 GSK143
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	pIC50: 7.5 (SYK) and 7.1 (pErk)[1]
ln Vitro	ZAP-70 (pIC50=4.7), LCK (pIC50=5.3), LYN (pIC50=5.4), JAK1/2/3 (pIC50=5.8/5.8/5.7), Aurora B (pIC50=4.8), hWB (pIC50=6.6), and hERG (pIC50=4.7) are all inhibited by GSK143 (compound 20)[1]. In CLL cells, GSK143 (10–10,000 nM; every 24 hours for three days) exhibits an IC50 of 323 nM. Early signaling processes, such as SYK phosphorylation and calcium flow, are abrogated by GSK 143 (1 μM; 30 mins)[2]. In bone marrow-derived macrophages, GSK143 (0.1–10 μM) decreases cytokine expression in a concentration-dependent manner lasting 30 minutes[3].
ln Vivo	In the intestinal muscularis, GSK143 (0.1–10 mg/kg; orally; 1.5 hours) decreases inflammation and inhibits the recruitment of immune cells[3]. The cutaneous reverse passive Arthus reaction is reduced by GSK143 (3, 10, 30, 100 mg/kg; oral; one hour before ovalbumin challenge) in a dose-dependent manner by around 50% and 70% at 10 mg/kg and 30 mg/kg, respectively[2]. GSK143 in rats has a T1/2 of 4.2 hours, a low clearance of 16 mL/min/kg, a moderate bioavailability of 30%, and a Vss of 4.1 L/kg (iv of 1 mg/kg; po of 3 mg/kg)[1].
Cell Assay	Cell Viability Assay[2] Cell Types: Chronic lymphocytic leukemia (CLL) cells Tested Concentrations: 10, 100, 1000, 10000 nM Incubation Duration: Every 24 h for 3 days Experimental Results: Had an IC50 of 323 nM.
Animal Protocol	Animal/Disease Models: Wild type C57NL/BL6 mice, 10-12 weeks old[3] Doses: 0.1, 1, 3, 10 mg/kg Route of Administration: po (oral gavage) 1.5 hrs (hours) before intestinal manipulation (IM) Experimental Results: decreased inflammation and prevented recruitment of immune cells in the intestinal muscularis. Animal/Disease Models: Male CD rats (175-200 g)[1] Doses: 1 mg/kg of iv; 3 mg/kg of po (pharmacokinetic/PK Analysis) Route of Administration: IV or PO Experimental Results: Had a T1/2 of 4.2 hrs (hours), low clearance (16 mL/min/kg), moderate bioavailability of 30% and a Vss of 4.1 L/kg.
References	[1]. Discovery of GSK143, a Highly Potent, Selective and Orally Efficacious Spleen Tyrosine Kinase Inhibitor. Bioorg Med Chem Lett. 2011 Oct 15;21(20):6188-94. [2]. Highly Selective SYK Inhibitor, GSK143, Abrogates Survival Signals in Chronic Lymphocytic Leukaemia. Br J Haematol. 2018 Sep;182(6):927-930. [3]. Inhibition of Spleen Tyrosine Kinase as Treatment of Postoperative Ileus. Gut. 2013 Nov;62(11):1581-90.
Additional Infomation	See also: Gsk143 (annotation moved to).

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	2.9206 mL	14.6028 mL	29.2056 mL
	5 mM	0.5841 mL	2.9206 mL	5.8411 mL
	10 mM	0.2921 mL	1.4603 mL	2.9206 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.