hsp

HSP-117 free base is a novel tachykinin NK1-receptor antagonist.

HSP-117 dihydrochloride is a novel tachykinin NK1-receptor antagonist.

Hsp70-derived octapeptide acetate (Hsp70-derived octapeptide acetate) is a group of tetratricopeptide repeat (TPR)-containing proteins has been shown to interact with the C-terminal domain of the 70 kDa heat-shock cognate protein (hsc70). In the present study, the effect of the TPR-containing proteins, including the C-terminus of hsc70-interacting protein (CHIP), TPR1 and human glutamine-rich TPR-containing protein (hSGT), on refolding of luciferase by DnaJ and hsc70 was investigated.

HSP70/SIRT2-IN-2 (Compounds 1a), a dual inhibitor of SIRT2 and HSP70, exhibits an IC50 of 45.1±5.0 μM against SIRT2 and demonstrates antitumor activity [1].

HSP90-IN-27, also known as compound 19, is an inhibitor of HSP90 [1].

HSP70/SIRT2-IN-1 (Compound 2a) serves as a dual inhibitor targeting both SIRT2 and HSP70, exhibiting an IC50 of 17.3±2.0 μM against SIRT2. This compound possesses antitumor activity [1].

HSP47 inhibitor III suppressed collagen type I expression in human and mouse cells and suppressed the viability and migration of lung fibroblasts.

HSP70-IN-1 is a heat shock protein (HSP) inhibitor and inhibits the growth of Kasumi-1 cells (IC50: 2.3 μM).

HSP90-IN-29 (Compound 13), a benzoxazole derivative, serves as a potent and selective HSP-90 inhibitor, exhibiting a low IC50 value of 30 nM. This compound demonstrates significant antitumor activity [1].

HSP27 inhibitor J2 (J2) (J2) is a HSP27 inhibitor, inhibits a production of HSP27 giant polymers, thereby having an effect of inhibiting a chaperone function of the HSP27 and reducing a cell protection function.

NVP-HSP990 (HSP990) is an effective and specific HSP90α/β inhibitor (IC50: 0.6 /0.8 nM).

Hsp90-IN-16 is an HSP90 inhibitor that acts effectively and highly selectively on HER2-positive cancer cells.Hsp90-IN-16 inhibits the proliferation of HCC1954 breast cancer cells with an IC50 value of 6 μM.Hsp90-IN-16 inhibits HSP90 client proteins, including a key oncogenic receptor HER2/neu, induced apoptosis in cancer cells.

HSP90-IN-23 (Comp 12-1), a heat shock protein 90 (HSP90) inhibitor, exhibits potent activity with an IC50 of 9nM. It promotes apoptosis in tumor cells and arrests their cell cycle at the G0/G1 phase, making it applicable for cancer research [1].

HSP90-IN-18 is a potent inhibitor of heat shock protein 90 (Hsp90), demonstrating significant inhibitory activity with an IC50 value of 0.39 μM. It is applicable in the research of viral infections, neurodegenerative diseases, and inflammation.

Hsp90-IN-15 is an Hsp90 inhibitor with anticancer effects. Hsp90-IN-15 blocks the cell cycle in S phase, induces apoptosis and reduces Hsp90 expression in Hela cells.

HSP90-IN-14 (compound 4) is an effective Hsp90 inhibitor (Kd=0.26 μM). In MDCK cells, HSP90-IN-14 showed anti-influenza virus activity, the EC50 against influenza A/H3N2, A/H1N1 and B virus was 2.6, 3.9 and 17 μM, respectively.

HDAC6/HSP90-IN-1 is a potent and selective dual inhibitor of HDAC6 (IC50: 4.3 nM) and HSP90 (IC50: 46.8 nM).HDAC6/HSP90-IN-1 downregulates PD-L1 expression in INF-γ-treated H1975 lung cancer cells.HDAC6/HSP90-IN-1 exhibits tumor growth inhibition in H1975 xenograft mice.HDAC6/HSP90-IN-1 is a potent and selective dual inhibitor of HDAC6 (IC50: 4.3 nM) and HSP90 (IC50: 46.8 nM). 1 exhibited tumor growth inhibition in H1975 xenograft mice.

Vibsanin A analog C (VAC) is an anti-cancer compound, which shows anti-proliferative effect on various cancer cell lines, and the anti-proliferative activity is the strongest among vibsanin A analogues. VAC fluctuated the amount of HSP90-related proteins in cells and showed an inhibitory effect on HSP90-mediated luciferase refolding in vitro.

Hsp90-IN-17 (Example 5) hydrochloride, an HSP90 inhibitor, has potential applications in the research of proliferative conditions including cancer and neurodegenerative diseases.

HSP90-IN-20, a potent inhibitor of HSP90, exhibits an IC50 of ≤10 μM, indicating its potential application in cancer research.

HDAC/HSP90-IN-3 is a selective and potent dual inhibitor of fungal Hsp90 (IC50: 0.83 μM) and HDAC (IC50: 0.91 μM), exhibiting antifungal effects against azole-resistant Candida albicans. HDAC/HSP90-IN-3 exhibits inhibitory effects on important virulence factors and is able to downregulate the resistance genes ERG11 and CDR1.

HSP90-IN-11 is a potent inhibitor of HSP90 and induces significant accumulation of the sub-G1 population. HSP90-IN-11 has a potent HSP90α inhibitory effect comparable to that of AUY-922 (Luminespib). In CRC and NSCLC cells, HSP90-IN-11 exhibited significant anti-proliferative activity in the double-digit nM range.HSP90-IN-11 was able to rapidly degrade client proteins EGFR and Akt in NSCLC cells.

HSP90-IN-25 (compound 4a) is an inhibitor targeting HSP90, specifically impeding its ATPase function [1].

MAO A/HSP90-IN-2 (compound 4-C), a dual inhibitor of HSP90 and MAO A, exhibits IC50 values of 0.016 μM for MAO A and 4.58 μM for HSP90. This compound not only enhances HSP70 expression but also diminishes HER2 and phospho-Akt levels, and downregulates IFN-γ-induced PD-L1 expression in GL26 cells. Demonstrating efficacy against Temozolomide-sensitive and -resistant GBM cells, colon cancer, leukemia, non-small cell lung cancer, and other malignancies, MAO A/HSP90-IN-2 may also impede tumor immune evasion [1].

HSP90-IN-13 (compound 5k) is a potent broad-spectrum inhibitor of HSP90 with an IC50 of 25.07 nM. HSP90-IN-13 has multitargeted activity against EGFR, VEGFR-2 and Topoisomerase-2. HSP90-IN-13 blocks the MCF-7 cell cycle in G2/M HSP90-IN-13 blocks the MCF-7 cell cycle in G2/M phase and induces apoptosis through a mitochondria-mediated pathway.

HSP90-IN-9 is a selective and potent HSP90 inhibitor.HSP90-IN-9 exhibits a dose-dependent fungicidal effect.HSP90-IN-9 in combination with FLC inhibits fungal biofilm formation and fungal morphological changes.HSP90-IN-9 downregulates ERG11, CDR1 and CDR2 gene expression and restores resistance to FLC. HSP90-IN-9 downregulates ERG11, CDR1 and CDR2 gene expression and restores FLC resistance.

HSP90-IN-22 (Compound 35) is an Hsp90 inhibitor exhibiting antiproliferative activity, with IC50 values of 3.65 μM in MCF7 breast cancer cells and 2.71 μM in SKBr3 breast cancer cells.

Compound X10g (PROTAC Hsp90α degrader 1) is a selective agent targeting Hsp90α for degradation and is utilized in breast cancer research. It demonstrates inhibitory effects on the proliferation of breast cancer cell lines, MDA-MB-231, MDA-MB-468, MCF-7, and MX-1, with respective IC50 values of 51.48 μM, 16.46 μM, 8.93 μM, and 11.95 μM [1].

PROTAC HSP90 degrader BP3 potently and selectively degrades HSP90 through a CRBN-dependent mechanism. It effectively diminishes HSP90 protein levels in MCF-7 cells with a half-maximal degradation concentration (DC50) of 0.99 µM. Additionally, this compound impedes the proliferation of breast cancer cells [1].

HSP70-IN-3, a potent inhibitor of HSP70 with IC50 values of 1.1 μM in ASZ001 cells and 1.9 μM in C3H10T1/2 cells, exhibits anti-Hedgehog (Hh) signaling and anti-proliferative activities. Furthermore, it reduces the expression of the oncogenic transcription factor GLI1 [1].

HDAC6/HSP90-IN-2 (compound 6e) is a dual inhibitor targeting HDAC6 and Hsp90, exhibiting IC50 values of 105.7 nM and 61 nM, respectively. It is primarily utilized in cancer research [1].

MAO A/HSP90-IN-1 (4-b) is a dual inhibitor of MAO A and HSP90, exhibiting IC50 values of 1.77 μM in glioblastoma (GBM) GL26 cells and 0.019 μM against HSP90α. This compound impairs the activities of MAO A, disrupts HSP90 binding, and downregulates both HER2 and phospho-Akt expressions, thereby inhibiting GBM growth. Additionally, it diminishes PD-L1 expression, thereby thwarting T cell activation and potential tumor immune evasion. MAO A/HSP90-IN-1 (4-b) is valuable for research into brain tumor-related diseases [1].

Aha1/Hsp90-IN-1 (Compound 17) is an inhibitor of the Aha1/Hsp90 complex and has an inhibitory effect on tau protein aggregation.Aha1/Hsp90-IN-1 disrupts the Aha1/Hsp90 interaction (IC50: 3.32 μM).

HSP90/mTOR-IN-1 is an effective and orally administrable inhibitor targeting both Hsp90 and mTOR, displaying IC50 values of 69 nM and 29 nM, respectively. This compound inhibits the proliferation of SW780 cells by overly activating the PI3K/AKT/mTOR pathway and induces apoptosis and autophagy through its selective inhibition of Hsp90 and mTOR. Additionally, HSP90/mTOR-IN-1 exhibits significant anti-tumor activity in vivo and is applicable in bladder cancer research.

HSP90-IN-19 is a potent inhibitor of heat shock protein 90 (Hsp90), exhibiting inhibitory activity with an IC50 of 0.27 μM. It is utilized in the research of viral infections, neurodegenerative diseases, and inflammation [1].

Hsp90-IN-17 (Example 5) is an inhibitor of HSP90, applicable in researching proliferative diseases, including cancer and neurodegenerative conditions.

HDAC/HSP90-IN-4 significantly inhibited HDAC and HSP90 activity, with compound 20 (HDACIC50= 194 nM; HSP90αIC50= 153 nM) and compound 26 ((HDACIC50= 360 nM; HSP90αIC50= 77 nM) having the strongest HDAC and HSP90α inhibition. effect. Both compounds induced HSP90 expression and down-regulated HSP90 client proteins, which play an important role in the regulation of cancer cell survival and invasion.

HSP90-IN-10 is a potent inhibitor of HSP90. HSP90-IN-10 exhibits potent anti-proliferative effects on HCC1954 breast cancer cells (IC50: 6 μM). hSP90-IN-10 induces apoptosis without inhibiting the growth of normal epithelial cells.

Pramiverine is a long-acting choline dissolving agent used for gastrointestinal spasms.

Luminespib (VER-52296) is a new-type inhibitor of HSP90 (IC50s: 7.8/21 nM for HSP90α/β in cell free assay).

Azadiradione (AZD) (AZD) from the methanolic extract of seeds of Azadirachta indica

Arimoclomol (BRX-220 free base) is a co-inducer of heat shock proteins (HSP) and can be used in studies about the treatment of amyotrophic lateral sclerosis (ALS).

Hsp90-Cdc37-IN-1 is an Hsp90-Cdc37 interaction disruptor (IC50: 140 nM) that inhibit cell migration and reverse drug resistance.

A group of tetratricopeptide repeat (TPR)-containing proteins has been shown to interact with the C-terminal domain of the 70 kDa heat-shock cognate protein (hsc70). In the present study, the effect of the TPR-containing proteins, including the C-terminus

Grp94 Inhibitor-1 is a potent, selective Grp94 inhibitor (IC50 : 2 nM).

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

VER-50589 is a potent HSP90 inhibitor.

Onalespib (AT13387) is a synthetic, orally bioavailable, small-molecule inhibitor of heat shock protein 90 (Hsp90) with potential antineoplastic activity. Onalespib selectively binds to Hsp90, thereby inhibiting its chaperone function and promoting the degradation of oncogenic signaling proteins involved in tumor cell proliferation and survival. Hsp90, a chaperone protein upregulated in a variety of tumor cells, regulates the folding, stability and degradation of many oncogenic signaling proteins.

Ganetespib (STA-9090) is a synthetic small-molecule inhibitor of heat shock protein 90 (Hsp90) with potential antineoplastic activity.

Geldanamycin, an HSP90 inhibitor (Kd: 1.2 μM), specifically disrupts glucocorticoid receptor (GR)/HSP association.