As a major outcome, two novel DOAC hits, namely the 1-(pyridin-4-yl)- (1) and 1-amidino- (23) isonipecotanilide derivatives, which proved to inhibit contemporarily thr/AChE and fXa/BChE, respectively, with inhibition constants in the low nanomolar range, deserve investigation in further ex vivo and in vivo animal models of AD and related cognitive impairments. The gene discussed is ACHE; the disease is Alzheimer disease.