heat shock proteins

Heat shock protein (Hsp) inhibitor II is the active form of Hsp inhibitor I and a benzylidene lactam compound that prevents the synthesis of inducible Hsps, such as Hsp105, Hsp72, and Hsp40. Hsp inhibitor II decreases Hsp72 synthesis in vivo and reduces thermotolerance of tumors in SCC VII tumor-containing mice. At 100 μM, it inhibits the development of thermotolerance in COLO 320 DM cells. Inhibition of Hsp70 with Hsp inhibitor II in combination with amphotericin B increases susceptibility of AmB-susceptible (MICs = 0.058 versus 0.27 μg/ml for combined and AmB alone, respectively) and AmB-resistant (MICs = 21.33 versus >32 μg/ml for combined and AmB alone, respectively) strains of A. fumigatus.

Luminespib (VER-52296) is a novel HSP90 inhibitor with IC50 values of 7.8 nM for HSP90α and 21 nM for HSP90β in a cell-free assay.

Ethoxyquin (Santoflex) is an antioxidant used in animal feeds.

Paeoniflorin (Peoniflorin) is a herbal constituent extracted from the root of Paeonia albiflora Pall.

2-hexyl-4-Pentynoic Acid, a valproic acid (VPA) derivatives, is a potent and robust HDACs inhibitor with IC50 value of 13 μM.

Palmitic acid (Cetylic acid) is a natural product, a common saturated fatty acid found in animals, plants and microorganisms. Palmitic acid has antitumor activity.

Novobiocin Sodium (Albamycinsodium) binds to DNA gyrase and blocks adenosine triphosphatase (ATPase) activity. Novobiocin sodium is an antibiotic compound derived from Streptomyces niveus. It has a chemical structure similar to coumarin.

Teprenone (Geranylgeranylacetone) is a anti-ulcer drug, and works as an inducer of heat shock proteins (HSPs).

Tamoxifen is an antineoplastic nonsteroidal selective estrogen receptor modulator (SERM).

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

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.

Arimoclomol (BRX-220 free base), a co-inducer of heat shock proteins (HSP), is utilized in studies on the treatment of amyotrophic lateral sclerosis (ALS).

Calenduloside E (Silphioside F) exhibits hypoglycemic activities by suppressing the transfer of glucose from the stomach to the small intestine and by inhibiting glucose transport at the brush border of the small intestine in oral glucose-loaded rats.

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.

Grp94 Inhibitor-1 is a potent and selective inhibitor of Grp94 with an IC50 of 2 nM.

Ganetespib (STA-9090) is a synthetic small-molecule inhibitor of heat shock protein 90 (Hsp90), exhibiting 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.

VER-50589 is a potent HSP90 inhibitor.

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.

Col003 is a selective and potent inhibitor of Hsp47, competitively binding to the collagen-binding site on Hsp47 (IC50: 1.8 μM). It is useful for researching fibrosis.

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).

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

Pimitespib (TAS-116) is an ATP-competitive and highly specific HSP90α HSP90β inhibitor with inhibition constants (Kis) of 34.7 nM and 21.3 nM, respectively.

NPX800 is an inhibitor of heat shock factor 1 (HSF1) and can be used in studies about the treatment of cancer.

KNK437 (Heat Shock Protein Inhibitor I), a pan-HSP inhibitor, suppresses the synthesis of inducible HSPs(HSP105, HSP72, and HSP40).

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.

DDO-5936 is a potent and specific inhibitor of the protein-protein interaction (PPI) between HSP90 and Cdc37.

HSP70-IN-1 is a heat shock protein (HSP) inhibitor that suppresses the growth of Kasumi-1 cells with an IC50 of 2.3 μM.

Alvespimycin hydrochloride (BMS 826476) is a potent HSP90 inhibitor with IC50 of 62 nM. Phase 2.

SD-169 (SD 169) is a selective and ATP competitive the MAP kinases p38α and p38β inhibitor.

VER-49009 (CCT 129397) is a potent Hsp90 inhibitor(IC50 of 25 nM and Kd of 78 nM).

VER-82576 (NVP-BEP800), a synthetic HSP90β inhibitor (IC50: 58 nM), exhibits >70-fold selectivity against Hsp90 family members Trap-1 and Grp94.

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.

YUM70 is a potent and selective inhibitor of glucose-regulated protein 78 (GRP78), with an IC50 of 1.5 μM for inhibiting GRP78 ATPase activity of the full-length protein. It induces endoplasmic reticulum (ER) stress-mediated apoptosis in pancreatic cancer.

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

HM03 is a potent and selective inhibitor of HSPA5 and exhibits anticancer activity.

KRIBB11 is an inhibitor of Heat Shock Factor (HSF) [inhibitor].

Feretoside is a natural product extracted from the barks of E. ulmoides. Feretoside shows inducible activity on the heat shock factor 1 (HSF1).

DTHIB robustly inhibits the HSF1 cancer gene signature and prostate cancer cell proliferation.

Delphinidin-3-O-galactoside chloride has anti-obesity and hypolipidemic effects. Delphinidin-3-O-galactoside (D3G) is a water-soluble anthocyanin with antioxidant activity. D3G is capable of masking the EGCG-induced cytotoxicity and ER stress, presumably

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

Dihydroberberine has anti-atherosclerotic, anti-inflammatory, hypolipidemic and antitumor activities. It inhibits human ether-a-go-go-related gene (hERG) channels and remarkably reduces Hsp90 expression and its interaction with hERG.

Apoptozole (Apoptosis Activator VII) inhibits the ATPase domain of Hsc70 and Hsp70, inducing apoptosis.

NDNA4 (compound 17) is a selective Hsp90α inhibitor (IC50: 0.34 μM) with permanent charge and low membrane permeability. It demonstrates minimal cytotoxicity against Ovcar-8 and MCF-10A cell lines (IC50 >100 μM) and maintains hERG channel maturation without triggering a heat shock response or degrading Hsp90α-dependent client proteins [1].

Flavokawain 1i, a derivative of chalcones flavokawain A, flavokawain B, and flavokawain C, exhibits anticancer and antiviral properties. At a concentration of 30 µM, it suppresses the growth of gefitinib-resistant H1975 non-small cell lung cancer (NSCLC) cells by 36% and modulates the protein expression by reducing the levels of heat shock protein 90 (Hsp90) client proteins, including EGFR, c-Met, HER2, Akt, and cyclin-dependent kinase 4 (Cdk4), while increasing the levels of Hsp70, indicative of Hsp90 inhibition. Additionally, intramuscular injection of flavokawain 1i lowers viral loads in pigs afflicted with porcine reproductive and respiratory syndrome virus (PRRSV).

ML346 is a novel activator of Hsp70.

JG-98 is an allosteric Hsp70 inhibitor, displays high active against the breast cancer cell lines MDA-MB-231 and MCF-7 (EC50s: 0.4 0.7 μM).

Rocaglamide (Roc-A), isolated from the genus Aglaia, can be used to treat coughs, injuries, asthma, and inflammatory skin diseases. It is a potent inhibitor of NF-κB activation in T-cells.