Table 3.
Preclinical studies of targeting HSP90
| Compound | Structure | Activity | Mechanism (Sites) |
|---|---|---|---|
| Geldanamycin |  |
Kd = 1215 nM | Pan-HSP90 inhibitor (NTD) |
| Radicicol |  |
Kd = 19 nM | Pan-HSP90 inhibitor (NTD) |
| HP-4 |  |
aIC50 = 18 nM | Pan-HSP90 inhibitor (NTD) |
| PU-3 |  |
bIC50 = 15–20 μM | Pan-HSP90 inhibitor (NTD) |
| SNX-2112 |  |
aIC50 = 3.0 nM | Pan-HSP90 inhibitor (NTD) |
| Compound 30 f |  |
bIC50 = 5.3 nM | Pan-HSP90 inhibitor (NTD) |
| XL888 derivative |  |
aIC50 = 57 nM | Pan-HSP90 inhibitor (NTD) |
| Capsaicin |  |
/ | Pan-HSP90 inhibitor (NTD) |
| Novobiocin |  |
cIC50 = 256 μM (MCF-7 cells) | Pan-HSP90 inhibitor (CTD) |
| Noviose sugar surrogates |  |
cIC50 = 560 nM (SKBr3 cells) | Pan-HSP90 inhibitor (CTD) |
| TVS21 derivative |  |
cIC50 = 3.1 μM (MCF-7 cells) | Pan-HSP90 inhibitor (CTD) |
| Compound 2n |  |
cIC50 = 9.5 μM (SKBr3 cells) | Pan-HSP90 inhibitor (CTD) |
| Deguelin |  |
cIC50 = 110 nM (H1299 cells) | Pan-HSP90 inhibitor (CTD) |
| HVH-2930 |  |
Kd = 97 µM | Pan-HSP90 inhibitor (CTD) |
| Penisuloxazin A |  |
/ | Pan-HSP90 inhibitor (CTD) |
| Enniatin A |  |
/ | Pan-HSP90 inhibitor (MD) |
| Diptoindonesin G |  |
Kd = 0.13 μM | Pan-HSP90 inhibitor (MD) |
| DN401 |  |
TRAP-1: Kd = 79 nM; HSP90α/β: Kd = 698 nM |
TRAP-1 selective inhibitor (NTD) |
| SMTIN-P01 |  |
/ | TRAP-1 selective inhibitor (NTD) |
| NECA |  |
GRP94: Kd = 0.53 μM; HSP90α: Kd = 46 μM |
GRP94 selective inhibitor (NTD) |
| PU-H39 |  |
GRP94: aIC50 = 2.4 μM; HSP90α/β: aIC50 = > 500 μM |
GRP94 selective inhibitor (NTD) |
| BnIm |  |
GRP94: aIC50 = 1.2 μM; HSSP90α: aIC50 = 1.4 μM |
GRP94 selective inhibitor (NTD) |
| KUNG65 |  |
GRP94: Kd = 0.54 μM; HSP90α: Kd = 39 μM |
GRP94 selective inhibitor (NTD) |
| ACO1 |  |
GRP94: Kd = 0.44 μM; HSSP90α: Kd = > 100 μM |
GRP94 selective inhibitor (NTD) |
| DDO-5813 |  |
GRP94: aIC50 = 2.0 nM; HSP90α: aIC50 = > 100 μM |
GRP94 selective inhibitor (NTD) |
| EC144 |  |
HSP90: Ki = 0.20 nM; TRAP1: Ki = 255 nM; GRP94: Ki = 61 nM |
HSP90α/β selective inhibitor (NTD) |
| Compound 31 |  |
HSSP90α/β: Ki = 5.0 nM; GRP94: Ki > 10 μM; TRAP1: Ki > 10 μM |
HSP90α/β selective inhibitor (NTD) |
| Gambogic acid |  |
HSP90β: Kd = 33 nM; HSSP90α: Kd = 195 nM |
HSP90β selective inhibitor (MD) |
| Corylin |  |
HSP90β: Kd = 24.7 nM | HSP90β selective inhibitor (MD) |
| KUNB31 |  |
HSP90β: Kd = 0.18 nM GRP94: Kd = 8.5 μM HSP90α: Kd = 9.6 μM |
HSP90β selective inhibitor (NTD) |
| KUNA-111 |  |
HSP90α: aIC50 = 0.25 μM; HSP90β: aIC50 = 3.8 μM | HSP90α selective inhibitor (NTD) |
| KUNA-115 |  |
HSP90α: aIC50 = 0.84 μM; HS90β: aIC50 = >50 μM |
HSP90α selective inhibitor (NTD) |
| NDNA4 |  |
eHSP90α: bIC50 = 0.34 μM | eHSP90 selective inhibitor (NTD) |
| DMAG-N-oxide |  |
/ | eHSP90 selective inhibitor (NTD) |
| STA-12-7191 |  |
/ | eHSP90 selective inhibitor (NTD) |
| Celastrol A |  |
cIC50 = 3.0 μM (Panc-1 cells) |
HSP90-CDC37 PPIs Inhibitor (NTD) |
| Pep-1 | KHFGMLRRWDD | Kd = 7.1 μM |
HSP90-CDC37 PPIs Inhibitor (NTD) |
| DDO-59120 | EKYEKQIK | Kd = 6.9 μM |
HSP90-CDC37 PPIs Inhibitor (NTD) |
| DDO-5936 |  |
HSP90: Kd = 7.4 μM |
HSP90-CDC37 PPIs Inhibitor (NTD) |
| DCZ3112 |  |
cIC50 = 7.9 μM (SK-BR-3 cells); cIC50 = 4.6 μM (BT-474 cells) |
HSP90-CDC37 PPIs Inhibitor (/) |
| HAM-1 |  |
Kd = 24 μM |
HSP90-Aha1PPIs Inhibitor (NTD) |
| CP9 |  |
/ |
HSP90-p23 PPIs Inhibitor (NTD) |
| Cucurbitacin D |  |
cIC50 = 0.60 μM (MCF-7 cells) | HSP90-p23 PPIs Inhibitor (/) |
| Y-632 |  |
/ |
HSP90-HOP PPIs Inhibitor (/) |
| SM145 |  |
/ |
HSP90-FKBPs PPIs Inhibitor (NTD, MD) |
| RNK05028 |  |
/ | Multi-specific molecules (NTD) |
| HEMTAC 26 |  |
CDK4/6: DC50 = 26/19 nM | Multi-specific molecules (NTD) |
| BP3 |  |
cIC50 = 0.60 μM (MCF-7 cells) | Multi-specific molecules (NTD) |
| X10g |  |
HSP90β: DC50 = 0.3 μM | Multi-specific molecules (NTD) |
| lw13 |  |
/ | Multi-specific molecules (NTD) |
Kd target binding affinity, Ki target binding affinity, aIC50 ATPase inhibitor activity, bIC50 competitive binding activity, cIC50 anti-proliferative activity, DC50 protein degradation activity, “/ “indicates no clear reports