IRAK4-IN-7 (CA-4948 analog; AU-4948) is a novel, potent, selective, and orally bioactive small molecule inhibitor of IRAK4 (interleukin-1 receptor-associated kinase 4) which has the potential to be used as a therapeutic agent for hematological cancers with dysregulated TLR/MYD88/IRAK4 signaling. It is an analog of Emavusertib (CA-4948). CA-4948 has high in vivo activity in a TLR4-induced cytokine release model. CA-4948 exhibits favorable DMPK properties, oral bioavailability, and is well tolerated in mice. Furthermore, CA-4948 was previously shown to exhibit dose-dependent efficacy in ABC-DLBCL MYD88-L265P xenograft tumor models using cell lines OCI-LY3 and OCI-LY10. IRAK4 kinase activity is required for toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) signaling in a variety of myeloid and lymphoid cell types. Recruitment of IRAK4 to these receptors and its subsequent activation is facilitated by the MYD88 adaptor protein, which is mutated in ~22% of DLBCL cases.

Physicochemical Properties

Molecular Formula	C21H19N7O3
Molecular Weight	417.420663118362
Exact Mass	417.154
CAS #	1801343-74-7
Related CAS #	1801344-14-8;2376399-42-5 (HCl);1801343-74-7 (CA4948-Analog);
PubChem CID	118224238
Appearance	Light brown to brown solid powder
LogP	1.5
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	9
Rotatable Bond Count	4
Heavy Atom Count	31
Complexity	620
Defined Atom Stereocenter Count	0
SMILES	O1CCN(C2=NC3=C(C=C(C=N3)NC(C3C=CC=C(C4C=NC(=CC=4)N)N=3)=O)O2)CC1
InChi Key	RWIMETUXCNDSLE-UHFFFAOYSA-N
InChi Code	InChI=1S/C21H19N7O3/c22-18-5-4-13(11-23-18)15-2-1-3-16(26-15)20(29)25-14-10-17-19(24-12-14)27-21(31-17)28-6-8-30-9-7-28/h1-5,10-12H,6-9H2,(H2,22,23)(H,25,29)
Chemical Name	6''-amino-N-(2-morpholinooxazolo[4,5-b]pyridin-6-yl)-[2,3''-bipyridine]-6-carboxamide
Synonyms	AU-4948; CA-4948 analog; CA 4948;AU 4948; AU4948; CA4948
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 Vivo	IRAK4-IN-7 can be utilized to treat inflammatory illnesses and cancer because of its anti-inflammatory and anti-cancer properties [1].
References	[1]. Bicyclic heterocyclyl derivatives as irak4 inhibitors. WO2015104688A1.
Additional Infomation	See also: Emavusertib (annotation moved to).

Solubility Data

Solubility (In Vitro)

DMSO: >30 mg/mL Water:N/A Ethanol:N/A

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 1.39 mg/mL (3.33 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 13.9 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.3957 mL	11.9783 mL	23.9567 mL
	5 mM	0.4791 mL	2.3957 mL	4.7913 mL
	10 mM	0.2396 mL	1.1978 mL	2.3957 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.