The compound (S)-1-(5-((2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-7-yl)sulfonyl)-3,4,5,6-tetrahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-3-hydroxy-2-phenylpropan-1-one, or a pharmaceutically acceptable salt thereof, is useful to increase the affinity of hemoglobin for oxygen. Methods and compositions for the treatment of a hemoglobinopathies are provided herein, including certain pharmaceutical compositions for activating PKR.