Syk-IN-4 is a potent, orally bioactive and selective SYK inhibitor (antagonist) with IC50 of 0.31 nM. SYK has emerged as a potential target in several research areas such as autoimmunity and hematological malignancies.

Physicochemical Properties

Molecular Formula	C21H25N9O
Molecular Weight	419.482902288437
Exact Mass	419.218
CAS #	2932264-95-2
PubChem CID	154573768
Appearance	White to off-white solid powder
LogP	1.9
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	6
Heavy Atom Count	31
Complexity	620
Defined Atom Stereocenter Count	0
InChi Key	IXNQUCOVJRJRGJ-UHFFFAOYSA-N
InChi Code	InChI=1S/C21H25N9O/c1-13-14(11-28(3)4)12-30(26-13)18-8-9-23-21(25-18)24-15-6-7-17-16(10-15)19(20(31)22-2)27-29(17)5/h6-10,12H,11H2,1-5H3,(H,22,31)(H,23,24,25)
Chemical Name	5-[[4-[4-[(dimethylamino)methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-N,1-dimethylindazole-3-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	IC50: 0.31 nM (SYK)[1]
ln Vitro	Syk-IN-4 is a strong inhibitor of hERG with an IC50 of 3.0 μM[1]. Syk-IN-4 suppresses SUDHL-4 and T cell proliferation with GI50s of 0.24 and 2.6 μM, respectively[1].
ln Vivo	When given orally (1 mg/kg), Syk-IN-4 has a moderate oral bioavailability (60%) in male Hans Wistar rats[1]. In male Hans Wistar rats, Syk-IN-4 shows significant plasma clearance (151 mL/min/kg) and huge volumes of distribution (1.0 L/kg, respectively) after intravenous injection (0.5 mg/kg)[1].
References	[1]. Optimization of a Series of Potent, Selective and Orally Bioavailable SYK Inhibitors. Bioorg Med Chem Lett. 2020 Jul 24;127433.

Solubility Data

Solubility (In Vitro)

DMSO: 62.5 mg/mL (148.99 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.96 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% 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 20.8 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: 2.08 mg/mL (4.96 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 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: ≥ 2.08 mg/mL (4.96 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 20.8 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	2.3839 mL	11.9195 mL	23.8390 mL
	5 mM	0.4768 mL	2.3839 mL	4.7678 mL
	10 mM	0.2384 mL	1.1920 mL	2.3839 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.