For both SHIN1/2 and AGF347, inhibition of both SHMT1 and SHMT2 was essential to their anti-tumor effects, as this prevents metabolic compensation for the loss of SHMT2 activity by reversal of the SHMT1 reaction and the synthesis of glycine and 5,10-methylene THF [150,153,161]. Here, SHMT1 is linked to neoplasm.