HSP (HSP90)

Signaling Pathway Map

Research Area

Inhibitory Selectivity

Isoform-specific Inhibitors

HSP (HSP90) Products

Catalog No. Information Product Use Citations Product Validations
S1141

Tanespimycin (17-AAG)

Tanespimycin (17-AAG, CP127374, NSC-330507, KOS 953) is a potent HSP90 inhibitor with IC50 of 5 nM in a cell-free assay, having a 100-fold higher binding affinity for HSP90 derived from tumour cells than HSP90 from normal cells. Tanespimycin (17-AAG) induces apoptosis, necrosis, autophagy and mitophagy. Phase 3.

S1069

Luminespib (NVP-AUY922)

Luminespib (AUY-922, NVP-AUY922) is a highly potent HSP90 inhibitor for HSP90α/β with IC50 of 13 nM /21 nM in cell-free assays, weaker potency against the HSP90 family members GRP94 and TRAP-1, exhibits the tightest binding of any small-molecule HSP90 ligand. Luminespib (AUY-922, NVP-AUY922) effectively downregulates and destabilizes the IGF-1Rβ protein and results in growth inhibition, autophagy and apoptosis. Phase 2.

S1142

Alvespimycin (17-DMAG) HCl

Alvespimycin (17-DMAG, NSC 707545, BMS 826476, KOS 1022) HCl is a potent HSP90 inhibitor with IC50 of 62 nM in a cell-free assay. Phase 2.

S1159

Ganetespib (STA-9090)

Ganetespib (STA-9090) is an HSP90 inhibitor with IC50 of 4 nM in OSA 8 cells, induces apoptosis of OSA cells while normal osteoblasts are not affected; active metabolite of STA-1474. Phase 3.

S0279New

Dimethylenastron

Dimethylenastron is a potent, specific and reversible inhibitor of kinesin Eg5 (kinesin-5/kinesin spindle protein, KSP) with IC50 of 200 nM. Dimethylenastron induces mitotic arrest and apoptosis and upregulate Hsp70 in human multiple myeloma cells.

S6721New

JG98

JG-98 is an allosteric inhibitor of Hsp70 that binds tightly to a deep pocket that is conserved in members of the Hsp70 family. JG-98 induces classical apoptosis features, including morphological changes consistent with programmed cell death and positive annexin staining. JG-98 exhibits anticancer activity.

S1175

BIIB021

BIIB021 (CNF2024) is an orally available, fully synthetic small-molecule inhibitor of HSP90 with Ki and EC50 of 1.7 nM and 38 nM, respectively. Phase 2.

S1163

Onalespib (AT13387)

Onalespib (AT13387) is a selective potent Hsp90 inhibitor with IC50 of 18 nM in A375 cells, displays a long duration of anti-tumor activity. Phase 2.

S1498

NVP-BEP800

NVP-BEP800 (VER82576) is a novel, fully synthetic HSP90β inhibitor with IC50 of 58 nM, exhibits>70-fold selectivity against Hsp90 family members Grp94 and Trap-1.

S2713

Geldanamycin

Geldanamycin (NSC 122750) is a natural existing HSP90 inhibitor with Kd of 1.2 μM, specifically disrupts glucocorticoid receptor (GR)/HSP association. Geldanamycin attenuates virus infection-induced ALI (acute lung injury)/ARDS (acute respiratory distress syndrome) by reducing the host's inflammatory responses.

S2639

SNX-2112 (PF-04928473)

SNX-2112 (PF-04928473) selectively binds to the ATP pocket of HSP90α and HSP90β with Ka of 30 nM and 30 nM, uniformly more potent than 17-AAG.

S2656

PF-04929113 (SNX-5422)

PF-04929113 (SNX-5422) is a potent and selective HSP90 inhibitor with Kd of 41 nM and induces Her-2 degradation with IC50 of 37 nM. Phase 1/2.

S2685

KW-2478

KW-2478 is a nonansamycin HSP90 inhibitor with IC50 of 3.8 nM. Phase 1.

S7122

XL888

XL888 is an ATP-competitive inhibitor of HSP90 with IC50 of 24 nM. Phase 1.

S2930

Pifithrin-μ

Pifithrin-μ (NSC 303580, PFTμ) is a specific p53 inhibitor by reducing its affinity to Bcl-xL and Bcl-2, and also inhibits HSP70 function and autophagy.

S7282

NMS-E973

NMS-E973 is a potent and selective Hsp90 inhibitor with DC50 of <10 nM for Hsp90 binding, no activiy against a panel of 52 diverse protein kinases.

S8039

PU-H71

PU-H71 is a potent and selective inhibitor of HSP90 with IC50 of 51 nM. Phase 1.

S5369

Ethoxyquin

Ethoxyquin (Santoquin, Santoflex, Quinol) is an antioxidant used as a food preservative. Ethoxyquin is an antioxidant which has been used in animal feed for many years and also an inhibitor of heat shock protein 90 (Hsp90).

S8365

Apoptozole

Apoptozole (Apoptosis Activator VII) is an inhibitor of heat shock protein 70(HSP70) and Hsc70 with dissociation constants Kd of 0.14 μM and 0.21 μM, respectively. It induces caspase-dependent apoptosis.

S8402

KRIBB11

KRIBB11 abolishes the heat shock-induced luciferase activity with an IC50 of 1.2 μM. It is an inhibitor of the transcription factor Heat Shock Factor 1 (HSF1). KRIBB11 induces growth arrest and apoptosis.

S7750

KNK437

KNK437 is a pan-HSP inhibitor, which inhibits the synthesis of inducible HSPs, including HSP105, HSP72, and HSP40.

S7458

VER-49009

VER-49009 (CCT0129397) is a potent HSP90 inhibitor with IC50 of 47 nM for HSP90β.

S7716

TAS-116

TAS-116 is a novel, small-molecule HSP90 inhibitor which inhibits geldanamycin-FITC binding to HSP90 proteins with Ki values of 34.7 nmol/L, 21.3 nmol/L, >50,000 nmol/L, and >50,000 nmol/L for HSP90α, HSP90β, GRP94, and TRAP1, respectively. Furthermore, TAS-116 does not inhibit other ATPases such as HSP70 (IC50 >200 μmol/L).

S7340

CH5138303

CH5138303 is an orally available Hsp90 inhibitor with Kd of 0.48 nM.

S7459

VER-50589

VER-50589 is a potent HSP90 inhibitor with IC50 of 21 nM for HSP90β.

S3604

Triptolide (PG490)

Triptolide (PG490) is a diterpene triepoxide, immunosuppresive agent extracted from the Chinese herb Tripterygium wilfordii. It functions as a NF-κB inhibitor with dual actions by disruption of p65/CBP interaction and by reduction of p65 protein. Triptolide (PG490) abrogates the transactivation function of heat shock transcription factor 1 (HSF1). Triptolide inhibits MDM2 and induces apoptosis through a p53-independent pathway.

S7751

VER155008

VER-155008 is a potent Hsp70 family inhibitor with IC50 of 0.5 μM, 2.6 μM, and 2.6 μM in cell-free assays for HSP70, HSC70, and GRP78, respectively, >100-fold selectivity over HSP90. VER155008 inhibits autophagy and causes reduced levels of HSP90 client proteins.

S0294New

HSF1A

HSF1A is a cell-permeable heat shock transcription factor 1 (HSF1) activator. HSF1A protects cells from stress-induced apoptosis, binds TRiC subunits and inhibits TRiC activity without perturbation of ATP hydrolysis.

S1972

Tamoxifen Citrate

Tamoxifen Citrate (ICI 46474) is an antagonist of the estrogen receptor by competitive inhibition of estrogen binding. Tamoxifen Citrate is also a potent Hsp90 activator and enhances the Hsp90 molecular chaperone ATPase activity. Tamoxifen induces apoptosis and autophagy.

S6568

ML346

ML346 is a Hsp70 activator and a novel modulator of proteostasis for protein conformational diseases.

S1238

Tamoxifen

Tamoxifen (ICI 46474) is an antagonist of the estrogen receptor in breast tissue. Tamoxifen enhances the Hsp90 molecular chaperone ATPase activity. Tamoxifen induces apoptosis.

S1052

Elesclomol (STA-4783)

Elesclomol (STA-4783) is a novel potent oxidative stress inducer that elicits pro-apoptosis events among tumor cells. Phase 3.

S8305

TRC051384

TRC051384 is an inducer of heat shock protein 70 (HSP70) and potent anti-inflammatory agent.

S8299

HA15

HA15 is a molecule that targets specifically BiP/GRP78/HSPA5. HA15 displays anti-cancerous activity on all melanoma cells tested, including cells isolated from patients and cells that developed resistance to BRAF inhibitors.

S5006

Teprenone

Teprenone, an acylic polyisoprenoid, that is known as tetraprenylacetone or geranylgeranylacetone, is an anti-ulcer drug, clinically used for gastritis. Teprenone(Geranylgeranylacetone) is an inducer of heat shock proteins (HSPs) expression.

Catalog No. Information Product Use Citations Product Validations
S1141

Tanespimycin (17-AAG)

Tanespimycin (17-AAG, CP127374, NSC-330507, KOS 953) is a potent HSP90 inhibitor with IC50 of 5 nM in a cell-free assay, having a 100-fold higher binding affinity for HSP90 derived from tumour cells than HSP90 from normal cells. Tanespimycin (17-AAG) induces apoptosis, necrosis, autophagy and mitophagy. Phase 3.

S1069

Luminespib (NVP-AUY922)

Luminespib (AUY-922, NVP-AUY922) is a highly potent HSP90 inhibitor for HSP90α/β with IC50 of 13 nM /21 nM in cell-free assays, weaker potency against the HSP90 family members GRP94 and TRAP-1, exhibits the tightest binding of any small-molecule HSP90 ligand. Luminespib (AUY-922, NVP-AUY922) effectively downregulates and destabilizes the IGF-1Rβ protein and results in growth inhibition, autophagy and apoptosis. Phase 2.

S1142

Alvespimycin (17-DMAG) HCl

Alvespimycin (17-DMAG, NSC 707545, BMS 826476, KOS 1022) HCl is a potent HSP90 inhibitor with IC50 of 62 nM in a cell-free assay. Phase 2.

S1159

Ganetespib (STA-9090)

Ganetespib (STA-9090) is an HSP90 inhibitor with IC50 of 4 nM in OSA 8 cells, induces apoptosis of OSA cells while normal osteoblasts are not affected; active metabolite of STA-1474. Phase 3.

S0279New

Dimethylenastron

Dimethylenastron is a potent, specific and reversible inhibitor of kinesin Eg5 (kinesin-5/kinesin spindle protein, KSP) with IC50 of 200 nM. Dimethylenastron induces mitotic arrest and apoptosis and upregulate Hsp70 in human multiple myeloma cells.

S6721New

JG98

JG-98 is an allosteric inhibitor of Hsp70 that binds tightly to a deep pocket that is conserved in members of the Hsp70 family. JG-98 induces classical apoptosis features, including morphological changes consistent with programmed cell death and positive annexin staining. JG-98 exhibits anticancer activity.

S1175

BIIB021

BIIB021 (CNF2024) is an orally available, fully synthetic small-molecule inhibitor of HSP90 with Ki and EC50 of 1.7 nM and 38 nM, respectively. Phase 2.

S1163

Onalespib (AT13387)

Onalespib (AT13387) is a selective potent Hsp90 inhibitor with IC50 of 18 nM in A375 cells, displays a long duration of anti-tumor activity. Phase 2.

S1498

NVP-BEP800

NVP-BEP800 (VER82576) is a novel, fully synthetic HSP90β inhibitor with IC50 of 58 nM, exhibits>70-fold selectivity against Hsp90 family members Grp94 and Trap-1.

S2713

Geldanamycin

Geldanamycin (NSC 122750) is a natural existing HSP90 inhibitor with Kd of 1.2 μM, specifically disrupts glucocorticoid receptor (GR)/HSP association. Geldanamycin attenuates virus infection-induced ALI (acute lung injury)/ARDS (acute respiratory distress syndrome) by reducing the host's inflammatory responses.

S2639

SNX-2112 (PF-04928473)

SNX-2112 (PF-04928473) selectively binds to the ATP pocket of HSP90α and HSP90β with Ka of 30 nM and 30 nM, uniformly more potent than 17-AAG.

S2656

PF-04929113 (SNX-5422)

PF-04929113 (SNX-5422) is a potent and selective HSP90 inhibitor with Kd of 41 nM and induces Her-2 degradation with IC50 of 37 nM. Phase 1/2.

S2685

KW-2478

KW-2478 is a nonansamycin HSP90 inhibitor with IC50 of 3.8 nM. Phase 1.

S7122

XL888

XL888 is an ATP-competitive inhibitor of HSP90 with IC50 of 24 nM. Phase 1.

S2930

Pifithrin-μ

Pifithrin-μ (NSC 303580, PFTμ) is a specific p53 inhibitor by reducing its affinity to Bcl-xL and Bcl-2, and also inhibits HSP70 function and autophagy.

S7282

NMS-E973

NMS-E973 is a potent and selective Hsp90 inhibitor with DC50 of <10 nM for Hsp90 binding, no activiy against a panel of 52 diverse protein kinases.

S8039

PU-H71

PU-H71 is a potent and selective inhibitor of HSP90 with IC50 of 51 nM. Phase 1.

S5369

Ethoxyquin

Ethoxyquin (Santoquin, Santoflex, Quinol) is an antioxidant used as a food preservative. Ethoxyquin is an antioxidant which has been used in animal feed for many years and also an inhibitor of heat shock protein 90 (Hsp90).

S8365

Apoptozole

Apoptozole (Apoptosis Activator VII) is an inhibitor of heat shock protein 70(HSP70) and Hsc70 with dissociation constants Kd of 0.14 μM and 0.21 μM, respectively. It induces caspase-dependent apoptosis.

S8402

KRIBB11

KRIBB11 abolishes the heat shock-induced luciferase activity with an IC50 of 1.2 μM. It is an inhibitor of the transcription factor Heat Shock Factor 1 (HSF1). KRIBB11 induces growth arrest and apoptosis.

S7750

KNK437

KNK437 is a pan-HSP inhibitor, which inhibits the synthesis of inducible HSPs, including HSP105, HSP72, and HSP40.

S7458

VER-49009

VER-49009 (CCT0129397) is a potent HSP90 inhibitor with IC50 of 47 nM for HSP90β.

S7716

TAS-116

TAS-116 is a novel, small-molecule HSP90 inhibitor which inhibits geldanamycin-FITC binding to HSP90 proteins with Ki values of 34.7 nmol/L, 21.3 nmol/L, >50,000 nmol/L, and >50,000 nmol/L for HSP90α, HSP90β, GRP94, and TRAP1, respectively. Furthermore, TAS-116 does not inhibit other ATPases such as HSP70 (IC50 >200 μmol/L).

S7340

CH5138303

CH5138303 is an orally available Hsp90 inhibitor with Kd of 0.48 nM.

S7459

VER-50589

VER-50589 is a potent HSP90 inhibitor with IC50 of 21 nM for HSP90β.

S3604

Triptolide (PG490)

Triptolide (PG490) is a diterpene triepoxide, immunosuppresive agent extracted from the Chinese herb Tripterygium wilfordii. It functions as a NF-κB inhibitor with dual actions by disruption of p65/CBP interaction and by reduction of p65 protein. Triptolide (PG490) abrogates the transactivation function of heat shock transcription factor 1 (HSF1). Triptolide inhibits MDM2 and induces apoptosis through a p53-independent pathway.

S7751

VER155008

VER-155008 is a potent Hsp70 family inhibitor with IC50 of 0.5 μM, 2.6 μM, and 2.6 μM in cell-free assays for HSP70, HSC70, and GRP78, respectively, >100-fold selectivity over HSP90. VER155008 inhibits autophagy and causes reduced levels of HSP90 client proteins.

Catalog No. Information Product Use Citations Product Validations
S0294New

HSF1A

HSF1A is a cell-permeable heat shock transcription factor 1 (HSF1) activator. HSF1A protects cells from stress-induced apoptosis, binds TRiC subunits and inhibits TRiC activity without perturbation of ATP hydrolysis.

S1972

Tamoxifen Citrate

Tamoxifen Citrate (ICI 46474) is an antagonist of the estrogen receptor by competitive inhibition of estrogen binding. Tamoxifen Citrate is also a potent Hsp90 activator and enhances the Hsp90 molecular chaperone ATPase activity. Tamoxifen induces apoptosis and autophagy.

S6568

ML346

ML346 is a Hsp70 activator and a novel modulator of proteostasis for protein conformational diseases.

S1238

Tamoxifen

Tamoxifen (ICI 46474) is an antagonist of the estrogen receptor in breast tissue. Tamoxifen enhances the Hsp90 molecular chaperone ATPase activity. Tamoxifen induces apoptosis.

Catalog No. Information Product Use Citations Product Validations
S1052

Elesclomol (STA-4783)

Elesclomol (STA-4783) is a novel potent oxidative stress inducer that elicits pro-apoptosis events among tumor cells. Phase 3.

S8305

TRC051384

TRC051384 is an inducer of heat shock protein 70 (HSP70) and potent anti-inflammatory agent.

S8299

HA15

HA15 is a molecule that targets specifically BiP/GRP78/HSPA5. HA15 displays anti-cancerous activity on all melanoma cells tested, including cells isolated from patients and cells that developed resistance to BRAF inhibitors.

Catalog No. Information Product Use Citations Product Validations
S5006

Teprenone

Teprenone, an acylic polyisoprenoid, that is known as tetraprenylacetone or geranylgeranylacetone, is an anti-ulcer drug, clinically used for gastritis. Teprenone(Geranylgeranylacetone) is an inducer of heat shock proteins (HSPs) expression.

Tags: HSP90 inhibition | HSP90 activity | HSP90 inhibitor cancer | HSP90 activation | HSP90 phosphorylation | HSP90 inhibitors in clinical trials | HSP70 assay | HSP70 phosphorylation | HSP90 inhibitor review