Table 1.

Top 10 hits from two HTS screens for p97 inhibitors

Assay IC50 (μM)*
Cell-based degradation assayATPase activity
Compound no. and IDUbG76V-GFPODD-LucLuc-ODCWTC522A
(1) CID16472035 CID6763522.6 ± 0.356 ± 1445 ± 111.5 ± 0.41.6 ± 0.3
2.3 ± 0.51.6 ± 0.2
(2) CID8868139.0 ± 1.343 ± 22>303 ± 0.82 ± 0.2
13 ± 21.2 ± 0.5
(3) JFD036651.1 ± 0.54.4 ± 1.0NM0.26 ± 0.058 ± 2
(4) CID67631.3 ± 0.53.3 ± 0.9NM3.5 ± 1.3ND
(5) JFD023423.4 ± 1.05.2 ± 1.811 ± 40.2 ± 0.0210 ± 4
(6) CID9343213.6 ± 0.718 ± 8NM1.3 ± 0.212 ± 1
(7) S097565.0 ± 1.017 ± 4NM0.8 ± 0.0820 ± 8
(8) JFD005976.6 ± 1.9NMNM6.1 ± 0.844 ± 12
(9) SEW051827.5 ± 2.9NMNM13 ± 130 ± 5
(10) CID110946810 ± 2NMNM2 ± 0.33 ± 0.2

NM, not measured due to interference with luciferase activity.

  • *Measurements were carried out in triplicate and the result expressed as mean ± SE.

  • Compounds with PubChem CID number are hits from the National Institutes of Health Molecular Libraries Small Molecule Repository. All other compounds are from the Maybridge HitFinder collection.

  • IC50 values of the resynthesized hits (SI Methods).