Table 1.
Inhibition of HSP90 alleviated various diseases by regulating PCD.
| Inhibitors | PCD | Mechanism | Disease | Reference |
|---|---|---|---|---|
| DHQ3 | necroptosis | Activating the cascade of RIP1-RIP3-MLKL to inducing necroptosis. | breast cancer | [58] |
| FW-04-806 | apoptosis | Down-regulating HSP90 clients (HER2, Akt, RAF-1) and their phosphorylated forms (P-HER2, P-Akt); Inducing apoptosis. | breast cancer | [36] |
| C0818 | apoptosis | Degrading the clients of HSP90; Inducing caspase-dependent apoptosis. | liver cancer | [144] |
| NVPAUG922 | apoptosis | Increasing the expression of LC3II; Inducing autophagy flux. | pancreatic cancer | [145] |
| SNX-2112 | apoptosis, autophagy | Down-regulating Bcl-2 and Bcl-XL, up-regulating Bid, cleavage- caspase-9, caspase-7, caspase-3 and PARP, and activating Caspase-8; Activating mitochondria mediated and death receptor-mediated apoptosis pathways. | melanoma | [115] |
| Gedunin | apoptosis | Adding sensitivity of A549 cells to apoptosis; Inhibitng the interaction between HSP90/Beclin-1/Bcl-2, leading to the down-regulation of autophagy (Beclin-1, ATG5-12 complex, and LC3) and anti-apoptotic protein Bcl-2. | lung cancer | [19] |
| 17-AAG | apoptosis | Down-regulating c-FLIPL to promoting apoptosis. | lung cancer | [39] |
| CUDC-305 | apoptosis | Inducing the degradation of receptor tyrosine kinases and downstream signaling molecules in the PI3K/AKT and RAF/MEK/ERK pathways. | lung cancer | [25] |
| Ganetespib | apoptosis | Target autophagy by destabilizing ATG7; Mediating autophagy by destabilizing ATG7. | non-small cell lung cancer | [112] |
| FS-108 | apoptosis | Affecting the drug resistance related proteins and their downstream Akt and Erk. | non-small cell lung cancer | [60] |
| 17-AAG | apoptosis | Inhibiting the NF-κB pathway. | chronic lymphocytic leukemia | [146] |
| 17-DMAG | apoptosis | Inhibiting mTOR pathway; Promoting the transformation from LC3 I to LC3 II. | myeloma | [108] |
| shHSP90 | apoptosis | Inhibiting the AKT/GSK3β/β-catenin signaling pathway and drug resistance of cancer cells. | ovarian carcinoma | [47] |
| Radicicol | apoptosis | Activating the caspase-8 and bid-dependent pathways and mitochondria-mediated apoptosis. | ovarian carcinoma | [98] |
| Curcumin | apoptosis | Inhibiting the toxic effect of MPP on SH-SY5Y cells; Reducing apoptosis. | parkinson’s disease | [23] |
| 17-AAG | necroptosis | Decreasing the activation of RIP1/RIP3/MLKL. | heat failure | [118] |
| GA | necroptosis | Decreasing the Hsp90 expression to promoting instability of RIP1. | ischemic injury | [40] |
| HSP90i | apoptosis | Reducing infarct size; Reducing Bax/Bcl-2 ratio. | ex vivo heart perfusion system | [147] |
| GA | apoptosis | Decreasing the expression of MLK3; Down-regulating the activation of JNK. | ischemic injury | [83] |
| 17AAG | apoptosis | Inhibiting IRE-1 to promoting the expression of HAX-1. | ischemic injury | [79] |
| GA | apoptosis | Decreasing infarct size, the expression of TNF-α, and apoptosis. | ischemic injury | [80] |
| GA | apoptosis | Decreasing the expression and activation of MLK3 and FasL; | ischemic injury | [48] |
| siHSP90 | apoptosis | Up-regulating Bcl-1 and down-regulating caspase-3 and Bax. | ischemic injury | [81] |
| 17AAG | necroptosis | Blocking the interaction of RIP1 and RIP3; Reducing the phosphorylation of RIP3. | acute respiratory distress syndrome | [120] |
HSP90 inhibitors acted on the degradation and activation of clients related to PCD, then promoting the treatment of disease.