YM-341619 (AS1617612) is a potent oral STAT6 inhibitor (antagonist) with IC50 of 0.70 nM. YM-341619 can inhibit IL-4-induced Th2 differentiation of mouse spleen T cells (IC50=0.28 nM), but does not affect the differentiation of Th1 cells. YM-341619 is a promising compound for research into allergic diseases, such as allergic asthma.

Physicochemical Properties

Molecular Formula	C22H21F3N6O2
Molecular Weight	458.436354398727
Exact Mass	458.167
CAS #	643082-52-4
PubChem CID	10321901
Appearance	Off-white to light yellow solid powder
LogP	3.4
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	10
Rotatable Bond Count	7
Heavy Atom Count	33
Complexity	635
Defined Atom Stereocenter Count	0
SMILES	N(C1=NC(NC2C=CC(N3CCOCC3)=CC=2)=NC=C1C(=O)N)CC1C(=CC=C(F)C=1F)F
InChi Key	IUUUCMFTTBSFIT-UHFFFAOYSA-N
InChi Code	InChI=1S/C22H21F3N6O2/c23-17-5-6-18(24)19(25)15(17)11-27-21-16(20(26)32)12-28-22(30-21)29-13-1-3-14(4-2-13)31-7-9-33-10-8-31/h1-6,12H,7-11H2,(H2,26,32)(H2,27,28,29,30)
Chemical Name	2-(4-morpholin-4-ylanilino)-4-[(2,3,6-trifluorophenyl)methylamino]pyrimidine-5-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

Targets	STAT6 0.70 nM (IC50)
ln Vitro	YM-341619 (0.1-100 nM; pretreatment 30 min before IL-4) suppresses IL-4-increased STAT6 luciferase gene activity in a concentration-dependent manner with an IC50 value of 1.5 nM in FW4 cells[2]. In T cells grown with IL-4, YM-341619 (0.1–10 nM; pretreatment 30 min before IL–4) concentration-dependently reduces IL–4 production and GATA-3 mRNA expression. Furthermore, it has no effect on T cells grown with IL-12 on the expression of T-bet (a Th1 transcription factor) mRNA or the generation of IFN-γ[2].
ln Vivo	The CLtot, t1/2, and Vd values of YM-341619 (intravenous injection; 1 mg/kg) are 36.1 mL/min/kg, 1.0 hour, and 3117 mL/kg, respectively. Additionally, in 8-week-old female balb/c mice, it displays Cmax, Tmax, AUC, and F% values of 80 ng/mL, 0.5h, 114 ng h/mL, and 25%, respectively[1]. The IgE level is dose-dependently suppressed by YM-341619 (oral administration; 0.003-0.03 mg/kg), but not the IgG2a level. YM-341619's ED50 value for the inhibition of IgE production is 0.026 mg/kg. In DNP-sensitized rats, YM-341619 tends to reduce IL-4 and IL-13 production in a dose-dependent way (both 57%), while it has no effect on IFN-γ production[2].
Cell Assay	RT-PCR[2] Cell Types: T cells Tested Concentrations: 0.1 nM, 1 nM, 10 nM Incubation Duration:Pretreatment 30 min before IL-4, then IL-4 treated for 16 hrs (hours) Experimental Results: diminished IL-4 and GATA-3 mRNA expression.
Animal Protocol	Animal/Disease Models: DNP-Ascaris-sensitized rats[1] Doses: 0.003- 0.03 mg/kg Route of Administration: Oral administration; 0.003-0.03 mg/kg Experimental Results: Suppressed IL-4 and IL-13 production in splenocytes derived from DNP-ascaris-sensitized rats without reducing IFN-γ production.
References	[1]. Identification of 4-benzylamino-2-[(4-morpholin-4-ylphenyl)amino]pyrimidine-5-carboxamide derivatives as potent and orally bioavailable STAT6 inhibitors. Bioorg Med Chem. 2008 Jul 1;16(13):6509-21. 9.15. [2]. YM-341619 suppresses the differentiation of spleen T cells into Th2 cells in vitro, eosinophilia, and airway hyperresponsiveness in rat allergic models. Eur J Pharmacol. 2008 Aug 20;590(1-3):409-16.

Solubility Data

Solubility (In Vitro)

DMSO: 50 mg/mL (109.07 mM)

Solubility (In Vivo)

Solubility in Formulation 1: 2.5 mg/mL (5.45 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.45 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (5.45 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.1813 mL	10.9066 mL	21.8131 mL
	5 mM	0.4363 mL	2.1813 mL	4.3626 mL
	10 mM	0.2181 mL	1.0907 mL	2.1813 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.