The PFKFB3 inhibitor 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one diminished the activation of the ERK pathway by downregulating lactate levels, and subsequently attenuated the increased spectrin breakdown product levels in the PASMCs of hypoxic mice and MCT-PAH rats.159 The ASK1 inhibitor GS-444217 was tested in MCT- and Su/Hx-PAH rats. Here, MAP3K5 is linked to pulmonary arterial hypertension.