IRAK inhibitor 1 is a potent IRAK-4 inhibitor with IC50 of 216 nM, is poorly active against JNK-1 and JNK-2 with IC50 of 3.801 μM, and >10 μM, respectively.

Physicochemical Properties

Molecular Formula	C17H19N5
Molecular Weight	293.36626
Exact Mass	293.164
CAS #	1042224-63-4
PubChem CID	44449078
Appearance	Light yellow to yellow solid powder
LogP	2.962
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	3
Heavy Atom Count	22
Complexity	357
Defined Atom Stereocenter Count	0
InChi Key	HUYUPQNBDBTPQQ-UHFFFAOYSA-N
InChi Code	InChI=1S/C17H19N5/c1-2-11-22-15(12-19-17(22)6-1)14-4-3-5-16(21-14)20-13-7-9-18-10-8-13/h1-6,11-13,18H,7-10H2,(H,20,21)
Chemical Name	6-imidazo[1,2-a]pyridin-3-yl-N-piperidin-4-ylpyridin-2-amine
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

Although less effective against JNK-1 and JNK-2, IRAK inhibitor 1 exhibits considerable activity in the IRAK-4 enzyme assay [1]. A recent addition to the IRAK family, IRAK-4 has special functional characteristics. The closest human homologue to Pelle is IRAK-4. Overexpression of IRAK-4 can activate the NF-κB and mitogen-activated protein (MAP) kinase pathways. Endogenous IRAK-4 interacts with IRAK-1 and TRAF6 in an IL-1-dependent manner. Most remarkably, IRAK-4 depends on its kinase activity to activate NF-κB, unlike other IRAKs. Moreover, IRAK-4 has the ability to phosphorylate IRAK-1, and dominant-negative IRAK-4 overexpression prevents IL-1-induced IRAK-1 activation and modification, suggesting that IRAK-4 is a key component of Toll/IL Early signaling by the -1 receptor (upstream of IRAK-1). Like other IRAKs, IRAK-4 can activate the NF-κB and MAPK signal transduction pathways. It also shares the same domain structure. It is not functionally redundant with IRAK-1, but it associates quickly and momentarily in an IL-1-dependent way with TRAF6 and IRAK-1. To activate NF-κB, IRAK-4, an active protein kinase, must have kinase activity. Upstream of IRAK-1, IRAK-4 may act as an IRAK-1 activator [2].

References

[1]. IRAK-4 inhibitors. Part II: A structure-based assessment of imidazo[1,2-a]pyridine binding. Bioorg Med Chem Lett. 2008 Jun 1;18(11):3291-5. [2]. IRAK-4: a novel member of the IRAK family with the properties of an IRAK-kinase. Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5567-72.

Solubility Data

Solubility (In Vitro)

DMSO : ~16.67 mg/mL (~56.82 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 1.67 mg/mL (5.69 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 16.7 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: ≥ 1.67 mg/mL (5.69 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 16.7 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: ≥ 1.67 mg/mL (5.69 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 16.7 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	3.4087 mL	17.0433 mL	34.0866 mL
	5 mM	0.6817 mL	3.4087 mL	6.8173 mL
	10 mM	0.3409 mL	1.7043 mL	3.4087 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.