TCS 21311 (NIBR3049) is a potent and selective JAK3 inhibitor (antagonist) with IC50 of 8 nM. Its selectivity is more than 100 times that of JAK1, JAK2 and TYK2. TCS 21311 (NIBR3049) inhibits PKCα, PKCθ and GSK3β with IC50s of 13, 68 and 3 nM respectively.

Physicochemical Properties

Molecular Formula	C27H25F3N4O4
Molecular Weight	526.5162
Exact Mass	526.183
CAS #	1260181-14-3
PubChem CID	50925411
Appearance	White to yellow solid powder
LogP	3.452
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	4
Heavy Atom Count	38
Complexity	1000
Defined Atom Stereocenter Count	0
InChi Key	CLGRAWDGLMENOD-UHFFFAOYSA-N
InChi Code	InChI=1S/C27H25F3N4O4/c1-26(2,38)25(37)34-11-9-33(10-12-34)15-7-8-19(27(28,29)30)17(13-15)21-22(24(36)32-23(21)35)18-14-31-20-6-4-3-5-16(18)20/h3-8,13-14,31,38H,9-12H2,1-2H3,(H,32,35,36)
Chemical Name	3-[5-[4-(2-hydroxy-2-methylpropanoyl)piperazin-1-yl]-2-(trifluoromethyl)phenyl]-4-(1H-indol-3-yl)pyrrole-2,5-dione
Synonyms	NIBR 3049 NIBR-3049 NIBR3049
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	TCS 21311 (NIBR3049) had IC50 values in the enzymatic Jak assay of 1.017, 2.550, and 8.055 μM for JAK1, JAK2, and TYK2, respectively [1]. According to its enzymatic Pkc activity [1], TCS 21311 (NIBR3049) exhibits moderate activity in this cell experiment (IC50=689 nM, Jurkat cells).
References	[1]. Identification of a potent Janus kinase 3 inhibitor with high selectivity within the Janus kinase family.J Med Chem. 2011 Jan 13;54(1):284-8.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~189.93 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (4.75 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 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 (4.75 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 (4.75 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	1.8993 mL	9.4963 mL	18.9926 mL
	5 mM	0.3799 mL	1.8993 mL	3.7985 mL
	10 mM	0.1899 mL	0.9496 mL	1.8993 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.