We exemplify the ISISS method by showing how coupling screening for target binding by fluorescence polarization with the reaction of acyl‐hydrazides and aldehydes led to the efficient discovery of a potent and novel acylhydrazone‐based inhibitor of human prolyl hydroxylase 2 (PHD2), a target for anemia treatment, with equivalent in vivo potency to an approved medicine. The gene discussed is EGLN1; the disease is anemia (phenotype).