hsp90

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

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

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-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].

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.

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].

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.

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].

MDK-0757 is a novel inhibitor of heat shock protein 90 (Hsp90).

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

IPI-493 (17-amino17demethoxy) is a novel HSP90 inhibitor with antitumor activity.

Quercetin, a flavonoid natural product, is a SIRT1 activator. It is also a PI3K inhibitor, inhibiting PI3Kγ, PI3Kδ, and PI3Kβ with IC50 values of 2.4, 3.0, and 5.4 μM, respectively. Recognized as a heat shock protein inhibitor, Quercetin can significantly reduce exosome release in TII models by downregulating Hsp70 or Hsp90.

PF-04929113 Mesylate (SNX-5422 Mesylate), a prodrug of SNX-2112, is an orally available Hsp90 inhibitor (Kd: 41 nM) and also induces Her-2 degradation (IC50: 37 nM).

DP-1 hydrochloride is a degradation product of SDC-TRAP-0063, a fragment of Ganetespib, a heat shock protein 90 (HSP90) inhibitor with antitumor activity.

Novobiocin is an orally active and potent antibiotic.Novobiocin is a DNA gyrase inhibitor and heat shock protein 90 (Hsp90) antagonist with inhibitory effects on gyrase and Hsp90. Novobiocin has anti-positive activity and can be used to study highly resistant pneumococcal infections.

PU-H71 HCl (Zelavespib HCl) is a novel Hsp90 inhibitor, a novel purine-based analog, and a radiosensitizer that may be a promising agent for CIRT. PU-H71 HCL shows antitumor activity in many preclinical models of malignancy. PU-H71 HCL has an inhibitory effect on the protein expression levels of Rad51 and Ku70, which may be associated with the double chain break repair in the homologous recombination pathway and non-homologous end-joining pathway.

DN401 is a potent TRAP1 and Hsp90 Inhibitor( IC50 = 79 nM for TRAP1, IC50 = 698 nM for Hsp90) with potent anticancer activity.

Shepherdin 79-87 acetate is a peptidomimetic antagonist of the complex between Hsp90 and survivin, another key regulator of tumor cell viability.

SNX0723 is a potent Hsp90 Inhibitor with anti-Plasmodium activity. SNX0723 shows high binding affinity for HsHsp90 and PfHsp90 with Kis of 4.4 and 47 nM, respectively. SNX0723 inhibits liver-stage P. berghei ANKA parasites with the EC50 of 3.3 μM.

Debio 0932 is an orally active inhibitor of HSP90 (IC50s: 100 and 103 nM for HSP90α and HSP90β, respectively).

HS-27 is a fluorescently-tethered inhibitor of Hsp90 with SNX-5422 tethered via a PEG linker to a fluorescein isothiocyanate or FITC. HS-27 can be used in see-and-treat paradigms.

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.

KW-2478 is a non-ansamycin HSP90 inhibitor with IC50 of 3.8 nM.

SNX2112 (PF 04928473) is an orally active Hsp90 inhibitor, with a Kd of 16 nM.

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.

Tanespimycin (KOS 953) (17-AAG) is an inhibitor of Hsp90 that selectively inhibits BT474 tumor cell Hsp90 (IC50: 5 nM).