Table 1. Affinity of Triazine and Pyrimidine Core-Containing Molecules to PI3K and PI3K-Related Kinases.

	binding constant Kd [nM]a
compd	PI3Kα	PI3Kβ	PI3Kγ	PI3Kδ	mTOR	PI3KC2β	VPS34	PI4KCβ	DNAPK	mTOR/PI3Kα
1	1.5	11	25	25	12	820	230	40000	1600	8.0
2	1.2	3.5	11	3.5	61	540	130	27000	>30000	51
3	1.0	3.5	24	76	0.94	0.46	5100	>30000	>30000	0.94
4	3.5	36	130	260	19	2100	200	40000	1800	5.4
5	0.76	2.1	7.7	3.3	48	40	nd	40000	1300	63
6	0.62	3.8	2.6	3.3	3.3	580	250	>30000	9800	5.3
	IC50, kinase assay [nM]b
compd	PI3Kα	PI3Kβ	PI3Kγ	PI3Kδ	mTOR	α542K/545K/1047Rc		VPS34	DNAPK	mTOR/PI3Kα
1	33	661	708	451	89	63/136/36		8486	8567	2.6
4	45	607	778	110	94	111/216/87		2581	6917	13

^aDissociation constants (K_d) were determined using ScanMax technology (DiscoveRx) ²⁶with 11-point 3-fold serial dilutions of the indicated compounds. K_d is the mean value from experiments performed in duplicate and calculated from standard dose–response curves using the Hill equation depicted in Experimental Section (n ≥ 2). A TreeSpot representation of a full kinase panel and kinase residual binding values are shown in Supporting Information Figure S1 and Table S2 for all above compounds except compound 2.

^bProkinase activity assays of the indicated enzymes and PI3Kα mutants.

^cInhibition of PI3Kα E542K, E545K, and H2047R mutant activities are indicated. For these values, the wild type PI3Kα reference IC₅₀ values were 122 nM for 1 and 142 nM for 4.