p97, an abundant hexameric ATPase of the AAA family, is involved in homotypic membrane fusion. It is thought to disassemble SNARE complexes formed during the process of membrane fusion. Two structures have been reported: a crystal structure of the N-terminal and D1 ATPase domains of murine p97 at 2.9 A resolution, and a cryoelectron microscopy structure of full-length rat p97 at 18 A resolution. Together, these structures show that the D1 and D2 hexamers pack in a tail-to-tail arrangement, and that the N domain is flexible. A comparison with NSF D2 (ATP complex) reveals possible conformational changes induced by ATP hydrolysis.
||NMS-873 is a potent, selective allosteric VCP/p97 inhibitor with IC50 value of 30 nM.
||ML241 hydrochloride is a potent p97 inhibitor, inhibiting p97 ATPase with IC50 value of 100 nM.
||ML240 is a selective, ATP-competitive p97 inhibitor with IC50 values of 100 nM.
||NMS-859 is a potent and specific small molecule covalent inhibitor of the ATPase VCP/p97 (IC50 ~0.37 μM), identified by high-throughput screening.
||DBeQ(JRF-12) is a selective, potent, reversible, and ATP-competitive p97 inhibitor with IC50 of 1.5 μM.