Table 3. PK, Cell Activity, and Kinase Selectivity of Selected Compounds.

Cpd	IRAK4 IC50 (nM)	Cell IC50a (nM)	Kinase Selectivityb	Pappc (×10–6 cm/s)	Solubilityd (μM)	Rat Cle (mL/min/kg)	Rat %Ff
12	18	78	96	12	26	–	–
13	67	292	96	18	23	75	4
16	27	141	99	5	12	88	0
18	11	375	94	7	63	98	0
19	19	187	90	29	21	45	13
26	85	333	96	9	8	43	2
31	93	580	97	15	13	51	42

^aSee Supporting Information for assay protocol.

^bPercent kinases with >100-fold selectivity (n = 111) versus IRAK, IC₅₀, see Supporting Information for additional details.

^cMeasured in LLC-PK1 cells.

^dMeasured kinetic solubility at pH 7.

^eIV dosed at 1 mg/kg as a solution of 1 mg/mL in 20% HPBCD.

^fPO dosed at 10 mg/kg as a suspension of 2 mg/mL in 0.4% methylcellulose. See Supporting Information for full PK parameters for compounds 19 and 31.