hsp90 inhibitor

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.

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.

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

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.

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).

TRAP1-IN-1 (compound 35) is a potent, selective TRAP1 inhibitor affecting the mitochondrial variant of Hsp90. It exhibits over 250-fold greater selectivity for TRAP1 compared to Grp94, destabilizes TRAP1 tetramers, and promotes the degradation of TRAP1 client proteins. Additionally, TRAP1-IN-1 impedes mitochondrial complex I activity involved in oxidative phosphorylation OXPHOS, compromises the mitochondrial membrane potential, and augments glycolytic metabolism [1].

PU-H54 is a purine-based inhibitor of Grp94. It is a Grp94-selective resorcinol-based inhibitor isolated through probing of the exclusive binding region of S2 subpocket in Grp94.

Gamitrinib TPP is a mitochondrial targeted HSP90 inhibitor exhibiting potent anti-cancer activity. Additionally, Gamitrinib TPP functions as a mitochondrial matrix inhibitor by targeting Gamitrinib (GA).

AT-533 is a potent inhibitor of Hsp90 and HSV. AT-533 blocks the HIF-1α/VEGF/VEGFR-2 signaling pathway, leading to suppress tumor growth and angiogenesis. AT-533 also inhibits the activation of the downstream pathways, including Erk1/2, FAK, Akt/mTOR/p70S6K,. AT-533 inhibits the cell migration, invasion, and the tube formation of human umbilical vein endothelial cells (HUVECs).

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

Aminohexylgeldanamycin (AHGDM) hydrochloride is a Geldanamycin derivative and a powerful inhibitor of HSP90. It exhibits significant antiangiogenic and antitumor properties.

NCT-58 is a potent C-terminal HSP90 inhibitor. NCT-58 does not induce the heat shock response (HSR). NCT-58 elicits anti-tumor activity via the simultaneous downregulation of HER family members as well as inhibition of Akt phosphorylation. NCT-58 kills Trastuzumab-resistant breast cancer stem-like cells. NCT-58 induces apoptosis in HER2-positive breast cancer cells.

BX-2819 is an Hsp90 inhibitor that exhibits potent antiproliferative activity with an IC50 of 41 nM . It effectively suppresses the growth of NCI-N87 and HT-29 tumor cells in nude mice[1].

H2-Gamendazole is a novel compound for spermatogenesis inhibition and cancer therapy as an inhibitor of heat shock proteins and/or elongation factor 1 alpha, and is an Hsp90 regulator.

MPC-0767, a potent, selective, and orally active hsp90 inhibitor, is the L-alanine ester prodrug of MPC-3100, exhibiting enhanced chemical stability.

Gamitrinib TPP hexafluorophosphate is a potent HSP90 inhibitor that specifically targets the mitochondria, demonstrating notable anti-cancer activity. It functions by inhibiting the mitochondrial matrix, making it an effective compound in cancer treatment.

Zelavespib (PU-H71) hydrochloride is a potent inhibitor of Hsp90, exhibiting an IC50 value of 51 nM in MDA-MB-468 cells.

Radicicol is an antifungal antibiotic, impairs mitochondrial replication by targeting P. falciparum topoisomerase VIB. Radicicol is an inhibitor of Hsp90 (IC50: 1 μM). Radicicol binds to the ATPase domain of Hsp90 and prevents maturation of Hsp90 clients,

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].

High affinity, potent and selective Hsp90 inhibitor

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.

Monorden diacetate a Hsp90 Inhibitor. Monorden diacetate is a Promising Lead Compound for the Development of Novel Fungicides.

DDO-5936 is a potent and specific HSP90-Cdc37 PPI inhibitor.

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.

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

17-GMB-APA-GA, a potent HSP90 inhibitor, is an ADC cytotoxin commonly employed for studying latent T. gondii infection.

Vibsanin A, an activator of protein kinase C (PKC) and an inhibitor of HSP90, demonstrates anti-proliferative effects on human cancer cell lines.

3-Phenyltoxoflavin (Phenyltoxoflavin) is an inhibitor of HSP90 (Kd = 585 nM) with anti-cancer activity.

BIIB021 (CNF2024) is an orally-available, fully synthetic inhibitor of HSP90(Ki=1.7 nM, EC50=38 nM).

Retaspimycin Hydrochloride is a potent and water-soluble Hsp90 inhibitor(Hsp90 and Grp9 with EC50s of 119 nM).

Shepherdin is a synthetic peptide mirroring amino acids 79-87 of human survivin, acting as an inhibitor of the survivin-heat shock protein 90 (Hsp90) interaction. It specifically targets the N-terminal domain of Hsp90, blocking the survivin-Hsp90 interaction in human reticulocyte extracts at a 150 µM concentration. Conjugates of Shepherdin with cell-permeable peptides, such as penetratin or the HIV Tat sequence, exhibit anticancer properties both in vitro and in vivo.

NSC145366 is an inhibitor of Hsp90 activities which targets the Hsp90 C-terminal domain to induce allosteric inhibition and selective client downregulation. NSC145366 increases Hsp90 oligomerization resulting in allosteric inhibition of NTD ATPase activity (IC50=119μM) but does not compete with NTD or CTD-ATP binding.

CH5164840 is a potent and selective HSP90 inhibitor. CH5164840 showed remarkable antitumor activity against NSCLC cell lines and xenograft models. CH5164840 has potent antitumor activity and is highly effective in combination with erlotinib against NSCLC tumors with EGFR overexpression and mutations.

Shepherdin 79-87, comprising amino acids 79 to 87 of Shepherdin, acts as a peptidomimetic antagonist targeting the Hsp90-Survivin complex, exhibiting anticancer properties.