PGAM1 inhibitor KH3 is a potent, allosteric small molecule inhibitor of phosphoglycerate mutase 1 (PGAM1) with IC50 of 105 nM.
KH3 binds to PGAM1 with Kd of 890 nM.
KH3 effectively suppresses pancreatic cancer cell proliferation (SW1990, PANC-1, AsPC-1, and MIA PaCa-2) with EC50 ranging from 0.27 to 0.70 uM, the primary pancreatic cancer cells are slightly more sensitive to KH3 with EC50 ranging from 0.22 to 0.43 uM.
KH3 inhibits PDAC cell growth by reducing glycolysis and mitochondrial respiration via targeting PGAM1.
KH3 targets similar signaling pathways in PANC-1 PDAC cells compared to PGAM1 knockdown.
KH3 attenuates PDAC growth in patient-derived xenograft (PDX) models.
