From: Targeting the Hsp90-Cdc37-client protein interaction to disrupt Hsp90 chaperone machinery
The potential approaches to disrupt the Hsp90-Cdc37-client protein interaction | Related mechanisms | References |
---|---|---|
Targeting Cdc37 | ||
 siRNAs or shRNA | Silencing Cdc37 | |
Targeting Cdc37-client interaction | ||
 4,5,6,7-Tetrabromobenzotriazole | CK2 inhibitors, suppressing Cdc37 phosphorylation at Ser13 site | [59] |
 PP5 mutation | Suppressing Cdc37 dephosphorylation | [48] |
 Vemurafenib | B-raf inhibitor. Antagonize Cdc37 interaction with kinases | [67] |
 Lapatinib | EGFR/HER2 inhibitor. Antagonize Cdc37 interaction with kinases | [67] |
Targeting Hsp90-Cdc37 interaction | ||
 Celastrol | Blocking the critical interaction of Hsp90 at Glu33 and Cdc37 at Arg167 | |
 Sulforaphane | Disrupting the formation of Hsp90-Cdc37 complex by direct modification of specific amino acids residues of Hsp90 | [70] |
 FW-04-804 | Binding sites at Gln133 and Glu47/Arg46 of Hsp90 | |
 Withaferin A | Blocking several H-bond between Hsp90-Cdc37 interaction, like Ser113 (Hsp90)-Gln208 (Cdc37) bond and Gln133 (Hsp90)-Arg166 (Cdc37) bond | |
 Kongensin A | Covalently binds to a cysteine 420 in the middle domain of Hsp90 and dissociates Hsp90 from Cdc37 | |
 Platycodin D | H-bond connection with Hsp90 at Arg32 and Phe200 and Cdc37 at Asp169 and Asp170 | |
 Pep-1 | Cdc37-derived peptides, bound to Hsp90 N-terminal domain and inhibited Hsp90 ATPase activity | [80] |