Table 1.

Promiscuous compounds from virtual and high-throughput screening

Structure	Type of screen	IC50 (μM) versus target	Experimental evidence for promiscuity	Reference
	Virtual screen	5 β-Lactamase	• Decreased inhibition with detergent	23, 24
			• Decreased inhibition with increased enzyme concentration
			• Inhibition of diverse enzymes
			• Time-dependent inhibition
			• Particles observed by DLS
a	Virtual screen	5 PMM/PGMb	• Decreased inhibition with detergent	28
			• Decreased inhibition with increased enzyme concentration
			• Time-dependent inhibition
			• Particles observed by DLS
	Virtual screen	25 Edema factor	• Decreased inhibition with increased enzyme concentration	29
			• Time-dependent inhibition
	Cell-based HTS	NDc EF-CaM	• Inhibition of diverse enzymes	31
	FRET-based HTS	7.4 Coronavirus proteinase	• Decreased inhibition with BSA	30
	Phase II clinical triald	1.6 PTP1b	• Decreased inhibition with detergent	32
			• Decreased inhibition with increased enzyme concentration
			• Time-dependent inhibition

^aDisperse Blue.

^bPMM/PGM, phosphomannomutase/phosphoglucomutase.

^cNot determined, compound observed to inhibit edema toxin-induced change in cellular morphology.

^dThe compound, ertiprotafib, had been studied in phase II trials prior to evaluation for promiscuity.³²