Pantothenate Kinase Inhibitor

Pantothenate Kinase Inhibitor (PANKi) is a reversible inhibitor of pantothenate kinase (PanK; IC₅₀s = 70, 92, and 25 nM for PanK1β, PanK2, and PanK3, respectively), the rate-limiting enzyme in the synthesis of coenzyme A .¹ It binds to the ATP-PanK3 complex with an apparent binding constant of 300 nM and exhibits mixed-type inhibition with respect to ATP and pantothenate. PANKi inhibits CoA biosynthesis in C3A cells (IC₅₀ = 0.9 µM) with no effect on cell viability when used at concentrations up to 8 µM. PANKi (5 µM) synergizes with BSO to induce ferroptosis in PANC-1 cells and sensitizes the cells to imidazole ketone erastin-induced ferroptosis.²

1.Sharma, L.K., Leonardi, R., Lin, W., et al.A high-throughput screen reveals new small-molecule activators and inhibitors of pantothenate kinasesJ. Med. Chem.58(3)1563-1568(2015) 2.Badgley, M.A., Kremer, D.M., Maurer, H.C., et al.Cysteine depletion induces pancreatic tumor ferroptosis in miceScience368(6486)85-89(2020)