Table 1.

Comparing irreversible analogues of 1–10 against GACKIX N627C.^[a]

Compound	Dose-response		Fold inhibition
		${\text{DR}}_{50}$ [mM]	MLL	pKID
1–10a		25	12±1	0.9±0.1
1–10b		150	13±1	1.4±0.2
1–10c		6.8	17±2	1.5±0.2
1–d		4.6	17±2	0.65±0.08
1–e		>500	14±2	0.88±0.09
1–f		>500	5.9±0.6	0.66±0.07

^[a]The ${\text{DR}}_{50}$ values were assessed by measuring the extent of GACKIX N627C labeled by means of Q-TOF LC-MS at various concentrations of compound. The fold inhibition values were obtained by comparing the dissociation constants ($K_{\text{D}}$) for the unlabeled (DMSO) KIX N627C construct with the $K_{\text{D}}$ values for the labeled KIX N627C–1–10 alkylator complex for both the MLL and pKID tracers. The $K_{\text{D}}$ values were measured from fluorescence polarization (FP) experiments that were performed in triplicate and errors reflect the standard deviation (SD) error.