HSP Inhibitor

AR/AR-V7 degrader-1 is an orally active AR and AR-V7 degrader. AR/AR-V7 degrader-1 disrupts the interaction between AR/AR-V7 and HSP90, leading to their ubiquitination and degradation in castration-resistant prostate cancer cells. AR/AR-V7 degrader-1 regulates the expression of cell cycle-related proteins in prostate cancer cells (downregulates CDK4, CDK6, Cyclin D1, Cyclin E1; upregulates P21) and induces G0/G1 phase arrest. AR/AR-V7 degrader-1 inhibits the proliferation and migration of prostate cancer cells. AR/AR-V7 degrader-1 suppresses the growth of castration-resistant prostate cancer tumors in nude mice and induces the degradation of AR and AR-V7 in tumor tissues. AR/AR-V7 degrader-1 is applicable to the research of castration-resistant prostate cancer.

HSP90-IN-11 is a HSP90 inhibitor with an IC₅₀ of 27.8 nM. HSP90-IN-11 inhibits the activity of HSP90, which in turn induces rapid degradation of EGFR and Akt proteins in non-small cell lung cancer (NSCLC) cells. HSP90-IN-11 induces accumulation of the G1 subphase cell population in NSCLC cells, activates caspase-3, caspase-8, caspase-9 and PARP, thereby triggering apoptosis. HSP90-IN-11 exhibits antiproliferative activity in colorectal cancer and NSCLC cells. HSP90-IN-11 can be used for the research of colorectal cancer and non-small cell lung cancer.

Hsp90-in-35 is an inhibitor of Hsp90, with an IC₅₀ between 0.05 and 0.5 μM. HSP90-IN-35 has antitumor activity. HSP90-IN-35 can be used to synthesize KRAS G12C degrader-1 (PROTAC) (HY-153881).

BX-2819 is a Hsp90 inhibitor with an IC₅₀ value of 41 nM. BX-2819 inhibits the proliferation of cancer cells. BX-2819 can significantly inhibit the growth of NCI-N87 and HT-29 tumors in nude mice.

Apidaecin IA acetate is a basic peptide. Apidaecin IA acetate inhibits the enzymatic activity of DnaK. Apidaecin IA acetate induces bacterial cell death. Apidaecin IA acetate can be used in research related to peritonitis and bacterial infections.

Hsp90-Cdc37-IN-2 (Compound 41) is an inhibitor for the interaction between heat shock protein 90 (Hsp90) and cyclin 37 (Cdc37). Hsp90-Cdc37-IN-2 inhibits the proliferation of cancer cell A549, MCF-7, HOS and HepG2 with IC₅₀ of 0.41-0.94 μM. Hsp90-Cdc37-IN-2 decreases the mitochondrial membrane potential, induces apoptosis, and arrest cell cycle at G0/G1 phase in A549.

EZH2/HSP90-IN-29 is a dual inhibitor for EZH2 and HSP90, with IC₅₀s of 6.29 nM and 60.1 nM, for EZH2 and HSP90, respectively. EZH2/HSP90-IN-29 increases apoptosis/necrosis-related gene expression, induces cell cycle arrest at M phase and inhibits reactive oxygen species (ROS) catabolism pathway. EZH2/HSP90-IN-29 is able to cross the blood-brain-barrier (BBB).

SM253 is an Hsp90 inhibitor that inhibits Hsp90-dependent protein folding. SM253 blocks chaperone function by binding to the N-middle linker region and the C-terminal M domain, reducing co-chaperone and client protein binding and activation. SM253 induces cancer cell apoptosis, activates caspase 3/7, causes cell cycle arrest and reduces cell proliferation, while decreasing Hsp90 client proteins such as AR, FKBP51, PSA, Cdk4, AKT, ERK, and p23, and reducing Hsp27/Hsp70 expression without inducing heat shock proteins. SM253 causes dose-dependent fibronectin loss in cells expressing LRP1. SM253 can be used for research on colon cancer, pancreatic cancer, and prostate cancer.

CH5164840 (16) shows high binding affinity for N-terminal Hsp90a (K_d = 0.52 nM) and strong anti-proliferative activity against human cancer cell lines (HCT116 IC₅₀ = 0.15 μM, NCI-N87 IC₅₀ = 0.066 μM). CH5164840 (16) is orally active (t_1/2 = 2.64 h) with potent antitumor efficacy.

VWK147 is a second-generation HSP90 C-terminal domain (CTD) inhibitor. VWK147 targets the CTD dimerization interface, prevents HSP90 CTD dimerization, disrupts co-chaperone PPID binding to HSP90 CTD, and inhibits HSP90 chaperone function dependent on dimerization. VWK147 reduces protein levels of HSP90 client proteins ULK1, RIPK1, and CDK4 without inducing a heat shock response. VWK147 induces cell death, including apoptosis, in Cisplatin (HY-17394)-sensitive and -resistant urothelial carcinoma cells. VWK147 induces LC3-II accumulation, inhibits autophagosome-lysosome fusion to block canonical autophagy, and induces non-canonical LC3 lipidation independent of ULK1 and PIK3C3 complexes. VWK147 can be used for the research of urothelial carcinoma.

HA15-Biotin is a chemical probe that consists of HA15 and biotin attached on the amide part of HA15. HA15-Biotin exhibits similar levels of activity to HA15. HA15-Biotin can be used for proteomic analysis.

17-Demethoxy-reblastatin (17-DR) is an inhibitor for heat shock protein 90 (Hsp90), with an IC₅₀ of 1.82 μM for yeast Hsp90 ATPase. 17-Demethoxy-reblastatin inhibits the proliferation of cancer cell HepG2 and SMMC7721, reduces the colony formation, and induces apoptosis through mitochondria and caspase mediated pathway.

NDNA3 (compound 14) is a selective inhibitor of Hsp90α (IC₅₀: 0.51 μM). NDNA3 is a permanently charged analog with low membrane permeability and low toxicity to Ovcar-8 (IC₅₀: 12.66 μM) and MCF-10A (IC₅₀: 11.72 μM) cells. NDNA3 prevents disruption of hERG channel maturation without generating a heat shock response or causing degradation of Hsp90α-dependent client proteins.

HSP90-IN-19 is an effective heat shock protein 90 (Hsp90) inhibitor. HSP90-IN-19 has effective Hsp90 inhibitory activity with an IC₅₀ value of 0.27 μM. HSP90-IN-19 can be used for the research of viral infection, neurodegenerative disease, and inflammation.

Radicicol 6-oxime (KF25706) is an Hsp90 inhibitor with an EC₅₀ of 5.5 nM against human Hsp90. Radicicol 6-oxime binds to Hsp90 and disrupts its chaperone function, leading to destabilization and depletion of Hsp90-associated signaling molecules. Radicicol 6-oxime depletes Hsp90-associated signaling proteins such as Raf-1, v-src, p185erbB2, Cdk4, and mutant p53, thereby inhibiting K-ras and v-src signaling pathways. Radicicol 6-oxime exhibits antiproliferative activity against various tumor cells. Radicicol 6-oxime inhibits tumor growth in mouse tumor xenograft models. Radicicol 6-oxime can be used for research on breast cancer, colon cancer, and vulvar epidermoid carcinoma.

Anti-Human/Mouse GRP78 Antibody (N88) is an anti-human/mouse GRP78 IgG1 monoclonal antibody. Anti-Human/Mouse GRP78 Antibody (N88) can activate the Akt signaling pathway. Anti-Human/Mouse GRP78 Antibody (N88) can inhibit the expression of inflammatory factors and plasminogen activator inhibitors induced by TLR agonists. Anti-Human/Mouse GRP78 Antibody (N88) can be used for research on inflammation conditions. Anti-Human/Mouse GRP78 Antibody (N88) can be used for immunoprecipitation.

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.

Hsp90-IN-48 is an orally active Hsp90 inhibitor with an IC₅₀ of 19.4 nM. Hsp90-IN-48 improves tumor-cell uptake and intracellular active-component release, and suppresses tumor metastasis. Hsp90-IN-48 induces G2/M phase cell cycle arrest and tumor cell apoptosis whlie simultaneously inhibits Top1/Top2 activity. Hsp90-IN-48 inhibits tumor growth and can be used for colon cancer research.

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.

HSP90/LSD1-IN-1 (compound 6) is a HSP90/LSD1 dual inhibitor. HSP90/LSD1-IN-1 inhibits the proliferation of prostate cancer cell lines PC-3 and DU145, with GI₅₀ values ​​of 0.24 and 0.30 μM, respectively.