HSP90 Inhibitor

CCT018159 is an ATP-competitive HSP90β inhibitor, with an IC₅₀ of 3.2 μM against human HSP90β ATPase and 6.6 μM against yeast HSP90β ATPase. CCT018159 induces cell cycle arrest and apoptosis in tumor cells, and inhibits invasion and angiogenesis. CCT018159 is applicable to cancer-related research.

Chetomin, an active component of Chaetomium globosum, is a heat shock protein 90/hypoxia-inducible factor 1 alpha (Hsp90/HIF1α) pathway inhibitor. Chetomin is a potent, nontoxic non-small cell lung cancer cancer stem cells (NSCLC CSC)-targeting molecule.

Ethoxyquin is an antioxidant which has been used in animal feed for many years and also an inhibitor of heat shock protein 90 (Hsp90).

VER-82576 (NVP-BEP800) is a potent, orally available and selective Hsp90 inhibitor, with an IC₅₀ of 58 nM for Hsp90β; VER-82576 also slightly blocks Grp94 and Trap-1, with IC₅₀s of 4.1 and 5.5 μM, respectively.

Cucurbitacin D is the active ingredient in Trichosanthes kirilowii and can disrupt the interaction between Hsp90 and two co-chaperones, Cdc37 and p23. Cucurbitacin D is an inflammasome activator. Cucurbitacin D induces cell cycle arrest and cell apoptosis, exhibiting anti-tumor and anti-inflammatory effects.

Debio 0932 (CUDC-305) is an orally active HSP90 inhibitor, with IC₅₀s of 100 and 103 nM for HSP90α and HSP90β, respectively.

NMS-E973 is a potent and selective inhibitor of HSP90. NMS-E973 binds to the ATP binding site of Hsp90α with a DC₅₀ of <10 nM. NMS-E973 is able to cross the blood-brain barrier (BBB). Antitumor efficacy.

VER-49009 is a Hsp90 inhibitor, with an IC₅₀ of 25 nM and a K_d of 78 nM.

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

Geldanamycin-FITC, a Geldanamycin fluorescent probe, can be used in a fluorescence polarization assay for HSP90 inhibitors. Geldanamycin-FITC also can be used for detection of cell surface HSP90 (Ex/Em = 488/515 nm).

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

VER-50589 is a Hsp90 inhibitor, with an IC₅₀ of 21 nM and a K_d of 4.5 nM.

NCT-58 is a potent inhibitor of C-terminal HSP90. NCT-58 does not induce the heat shock response (HSR) due to its targeting of the C-terminal region and 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.

Icapamespib (PU-HZ151; PU-AD) is a selective, orally active inhibitor of Epichaperomes assembled by HSP90 with slow dissociation kinetics. Icapamespib can cross the blood-brain barrier (BBB) ??and induce epichaperome disassembly by non-covalently binding to HSP90, restoring the normal protein-protein interaction network. Icapamespib can specifically disrupt disease-related abnormal protein interaction networks, reduce neurotoxic protein aggregation and tumor cell survival signals. Icapamespib can be used in the research of neurodegenerative diseases such as Alzheimer's disease, as well as cancers such as glioblastoma and metastatic breast cancer.

Regaloside C is an anti-inflammatory agent and antioxidant that scavenges ABTS and DPPH free radicals. Regaloside C targets multiple molecules including TNF-α, MMP-2, ERα, AKT1, TLR4 and HSP90-α. Regaloside C is applicable to research related to inflammatory diseases.

DN401 is a potent TRAP1 inhibitor with an IC₅₀ of 79 nM. DN401 shows a weak inhibition of Hsp90 (IC₅₀ of 698 nM). DN401 inactivates mitochondrial TRAP1 and has potent anticancer activities.

Icapamespib (PU-HZ151; PU-AD) hydrochloride is a selective, orally active inhibitor of Epichaperomes assembled by HSP90 with slow dissociation kinetics. Icapamespib hydrochloride can cross the blood-brain barrier (BBB) ??and induce epichaperome disassembly by non-covalently binding to HSP90, restoring the normal protein-protein interaction network. Icapamespib hydrochloride can specifically disrupt disease-related abnormal protein interaction networks, reduce neurotoxic protein aggregation and tumor cell survival signals. Icapamespib hydrochloride can be used in the research of neurodegenerative diseases such as Alzheimer's disease, as well as cancers such as glioblastoma and metastatic breast cancer.

Ursolic acid acetate (Acetylursolic acid) is a triterpenoid compound and an inhibitor of Plasmodium falciparum heat shock protein 90 (PfHsp90) with a K_D of 8.16 μM. Ursolic acid acetate is cytotoxic to KB cells, with an IC₅₀ value of 8.4 μM. Ursolic acid acetate can be used in tumor and antimalarial research.

3-Phenyltoxoflavin, a derivative of Toxoflavin, is an Hsp90 inhibitor, with a K_d of 585 nM for the interaction of Hsp90-TPR2A. 3-Phenyltoxoflavin has anti-cancer activity.

Wighteone (6-Isopentenylgenistein; Erythrinin B) is a prenylated isoflavone that acts as a HSP90/EGFR^L858R/T790M inhibitor and antifungal agent. Wighteone reduces the expression level of HSP90, blocks EGF-induced phosphorylation of EGFR, and thereby inhibits the downstream ERK and AKT signaling pathways. Wighteone induces cell cycle redistribution, inhibits proliferation and triggers apoptosis in cancer cells. Wighteone can be isolated from Erythrina suberosa, and can also be induced to synthesize in Lotus japonicus under specific conditions. Wighteone can be used to study HER2-positive breast cancer, leukemia, non-small cell lung cancer with EGFR^L858R/T790M mutation, and fungal infections.