HSP70 Inhibitor

EV206 is a Hsp70 binder and apoptosis inducer that binds to the N-terminal domain of Hsp70, promotes Hsp70 degradation via the ubiquitin-proteasome system, and reduces Hsp70 protein stability. EV206 induces apoptotic cell death, inhibits colony formation, and downregulates the expression of cancer stem cell-related markers in non-small cell lung cancer cells. EV206 inhibits the growth of H460 xenograft tumors in nude mice and can be used for the research of non-small cell lung cancer.

HSP70-IN-8 (Compound 1b) is a HSP70 inhibitor and Alpinetin (HY-N0625A) derivative. HSP70-IN-8 inhibits the expression of HSP70 protein.HSP70-IN-8 exhibits excellent anti-liver cancer activity.

Hsp70/FoxM1-IN-1 (Compound 7d) is a potent heat shock protein 70 (Hsp70) and Forkhead box M1 (FoxM1) dual inhibitor. Hsp70/FoxM1-IN-1 demonstrates significant antiproliferative and pro-apoptotic effects in multiple solid tumor models (e.g., breast, colorectal cancer), particularly for tumors co-overexpressing Hsp70/FoxM1.

Ly101-4B is an apoptosis inducer and multi-target inhibitor with antiproliferative, antitumor and cycytotoxic effects. Ly101-4B reduces HSF1 expression, inhibits microRNA-214 synthesis, downregulates HSP27, HSP70 and HSP90 expression, while suppressing E2F-dependent transcriptional activity and downregulating its target genes. Ly101-4B induces caspase 3/7-mediated apoptosis by reducing DNA synthesis, inhibiting the cell cycle and G1/S phase transition, without affecting RNA synthesis or inducing necrosis. Ly101-4B is selective for pancreatic ductal adenocarcinoma cells with different genotypes and varying degrees of E2F dependence. Ly101-4B can be used in research related to epithelial ovarian cancer and pancreatic ductal adenocarcinoma.

A17 peptide is a Hsp70-targeting peptide. A17 peptide binds to the ATP-binding domains of Hsp70. A17 peptide specifically inhibits the chaperone activity, thereby increasing the cells' sensitivity to apoptosis induced by chemotherapeutic agents, such as Cisplatin (HY-17394). A17 peptide can be used for anticancer chemotherapy research, such multiple myeloma.

HIF-2α-IN-17 is a selective hypoxia-inducible factor 2α (HIF2α) inhibitor that binds to the PAS-B domain of HIF2α. HIF-2α-IN-17 disrupts the interaction between HIF2α and the molecular chaperone Hsp70, leading to proteasomal degradation of HIF2α. HIF-2α-IN-17 exhibits antitumor activity and induces apoptosis in cancer cells. HIF-2α-IN-17 is applicable for research on cancers such as clear cell renal cell carcinoma.

Versipelostatin is a GRP78/Bip molecular chaperone down-regulator and can be isolated from the culture broth of Streptomyces versipellis 4083-SVS6.

YM-08 (Compounds 7a) is a brain-penetrant inhibitors of SIRT2,with the IC₅₀ of 19.9 μM. YM-08 also is inhibitor of Hsp70.

HDAC/HSP90-IN-1 (compound 20) is a potent dual inhibitor of HDAC (IC₅₀ = 194 nM) and HSP90 (HSP90α IC₅₀ = 153 nM). HDAC/HSP90-IN-1 induces HSP70 expression, downregulates HSP90 client proteins, and promotes acetylation of α-tubulin and histone H3 in cancer cells. HDAC/HSP90-IN-1 reduces PD-L1 expression in IFN-γ treated H1975 cells. HDAC/HSP90-IN-1 can be used for cancer research, such as lung and colon cancer.

DMT003096 is a HSP70 inhibitor. HSP70 has been reported to be upregulated in various cancers including breast, lung, colon, and cervix.

STA-1474 is an orally active and highly selective HSP90 inhibitor, as well as a phosphate prodrug of the HSP90 inhibitor STA-9090 (HY-15205). STA-1474 disrupts the chaperone function of HSP90 and promotes the degradation of client proteins. STA-1474 inhibits the phosphorylation of Met, Akt and STAT3, thereby blocking related signaling pathways. STA-1474 induces apoptosis and inhibits proliferation of osteosarcoma cells, and triggers the up-regulation of HSP70 and HSP90. STA-1474 induces tumor regression and caspase-3 activation in mouse osteosarcoma xenograft models. STA-1474 can be used in the research of osteosarcoma.

HSP70-IN-6 (JL-15) is an inhibitor of Hsp70-Bim protein-protein interaction, with an IC₅₀ value of 0.07 μM against Hsp70-Bim PPI, an IC₅₀ of 4.89 μM and a K_d of 0.123 μM for BimBH3-stimulated Hsp70 ATPase activity. HSP70-IN-6 selectively blocks the binding of Hsp70-Bim without affecting the Hsp70-Bag3 interaction, and inhibits BimBH3-stimulated Hsp70 ATPase activity but has no impact on basal ATPase activity. HSP70-IN-6 induces apoptosis (apoptosis) in chronic myeloid leukemia cells in an Hsp70-Bim-dependent manner. HSP70-IN-6 can be used in research related to chronic myeloid leukemia.

HDAC/HSP90-IN-2 (compound 26) is a potent dual inhibitor of HDAC (IC₅₀ = 360 nM) and HSP90 (HSP90α IC₅₀ = 77 nM). HDAC/HSP90-IN-2 induces HSP70 expression, downregulates HSP90 client proteins, and promotes acetylation of α-tubulin and histone H3 in cancer cells. HDAC/HSP90-IN-2 reduces PD-L1 expression in IFN-γ treated H1975 cells. HDAC/HSP90-IN-2 can be used for cancer research, such as lung and colon cancer.

HSP70-IN-7 is a nonselective HSP70 inhibitor with K_ds of 4.71, 2.16 and 2.93μM against HSP70, GRP75, and GRP78. HSP70-IN-7 exhibits selective toxicity against breast cancer cells, induces cell apoptosis and effectively suppresses the properties of breast cancer stem cells (BCSCs). HSP70-IN-7 can be used for the study of breast cancer.

GRP78-IN-1 exhibits several interactions with GRP78 residues with binding energy of -8.07 kcal/mol. GRP78-IN-1 shows the potent cytotoxic, anti-proliferative in cancer cells. GRP78-IN-1 exhibits promising apoptosis in breast cancer cells and stalls wound healing properties.

HSP70/SIRT2-IN-1 (Compounds 2a) is a dual inhibitor for SIRT2 and HSP70, with IC₅₀ of 17.3±2.0 μM for SIRT2. HSP70/SIRT2-IN-1 has antitumor activity.

YM-1 tosylate is a stable MKT-077 (HY-15096) analog and an orally active Hsp70 inhibitor. YM-1 tosylate induces cell death of HeLa cells and up-regulates the level of p53 and p21 proteins.

HSF1-IN-3 is a heat shock transcription factor 1 (HSF1) inhibitor with a K_d value of 23.8 μM against HSF1-DBD. HSF1-IN-3 inhibits the proliferation of cancer cells and induces their apoptosis, with stronger activity in androgen-dependent prostate cancer cells. HSF1-IN-3 reduces the expression of HSP70 and HSP90, downstream effectors of HSF1, and attenuates HSE-driven transcriptional activity. HSF1-IN-3 can be used in the research of cancers such as prostate cancer and leukemia.

STA-1474 sodium is an orally active and highly selective HSP90 inhibitor, as well as a phosphate prodrug of the HSP90 inhibitor STA-9090 (HY-15205). STA-1474 sodium disrupts the chaperone function of HSP90 and promotes the degradation of client proteins. STA-1474 sodium inhibits the phosphorylation of Met, Akt and STAT3, thereby blocking related signaling pathways. STA-1474 sodium induces apoptosis and inhibits proliferation of osteosarcoma cells, and triggers the up-regulation of HSP70 and HSP90. STA-1474 sodium induces tumor regression and caspase-3 activation in mouse osteosarcoma xenograft models. STA-1474 sodium can be used in the research of osteosarcoma.

EG36 is a selective E. coli DnaK inhibitor that inhibits DnaK ATPase activity at a concentration of 100 μM. EG36 directly binds to the nucleotide-binding domain (NBD) of E. coli DnaK by disrupting the DnaK-DnaJ interaction. EG36 can be used for research on bacterial infectious diseases.