Monoketone analogs of curcumin form a new class of FA pathway inhibitors. A) Identification of 4H-TTD in an independent screen for FA pathway inhibitors. Each compound of row E of the NCI Challenge Set library plate was tested at 0.5 mM in Xenopus extracts for inhibition of xFANCD2-ub and xMRE11-P. Arrow indicates the active compound. The chemical structure of 4H-TTD is shown. B) Comparison of xFANCD2-Ub inhibition activity of 4H-TTD, EF24 and curcumin in Xenopus extracts. xFANCD2-Ub IC50 were determined as in Fig. 1A. C) 4H-TTD inhibits the FA pathway in HeLa cells. IC50 was determined as in Fig. 4A. D) 4H-TTD is more toxic to 309ATM KO than 334ATM WT cells.