hsp90 a.1

MAO A HSP90-IN-1 (4-b) is a dual inhibitor of MAO A and HSP90, with IC50 values of 1.77 μM in glioblastoma (GBM) GL26 cells and 0.019 μM against HSP90α. This compound impairs MAO A activity, disrupts HSP90 binding, and downregulates HER2 and phospho-Akt expressions, thus inhibiting GBM growth. Additionally, it reduces PD-L1 expression, thwarting T cell activation and potential tumor immune evasion. MAO A HSP90-IN-1 (4-b) is valuable for research into brain tumor-related diseases [1].

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.

KU-177 is a Hsp90 ATPase homolog 1 (Aha1) inhibitor. By disrupting the interaction between Hsp90 and Aha1, it prevents the proliferation of primary MM and relapsed MM patient samples. It eliminates the proliferation and PI resistance induced by AHSA1 elevation.

Radicicol (Monorden) is an antifungal antibiotic and a potent inhibitor of heat shock protein 90 (Hsp90), which leads to the degradation of Hsp90 by the proteasome by binding to its ATP-binding pocket. In addition, Radicicol inhibits the growth and proliferation of several tumor cell lines. It also has anti-malarial activity and acts as an inhibitor of adipose- and obesity-related proteins (FTO). Radicicol inhibits iNOS gene expression by blocking the p38 kinase signaling pathway and NF-kB/Rel

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

Hsp90-IN-34 (compound HAM-1) is a chemical inhibitor that targets the Aha1-Hsp90 chaperone complex with high affinity (KDapp=23.5 µM). It modulates the ATPase activity of Hsp90 by affecting the interaction between Hsp90 and Aha1.

CYP51 Hsp90-IN-1 (Compound MM4) is a dual inhibitor of CYP51 and Hsp90. This compound exhibits antifungal activity against Candida albicans and effectively suppresses key fungal virulence factors. CYP51 Hsp90-IN-1 shows potential for research in treating invasive candidiasis.

HEMTACWEE1degrader-1 is a WEE1-targeting heterobifunctional chimeric degrader (HEMTAC) facilitated by HSP90, exhibiting an HSP90 enzyme inhibitory activity with an IC50 of 16.76 nM. It enhances the ubiquitination and subsequent degradation of WEE1, effectively blocking the G2/M cell cycle transition. This compound shows anticancer properties in patient-derived xenograft (PDX) models of acute myeloid leukemia (AML). HEMTACWEE1degrader-1 is utilized in AML research.

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

CAY10747 is an inhibitor of the protein-protein interaction between heat shock protein 90 (Hsp90) and cell division cycle 37 (Cdc37) and a derivative of celastrol .1It decreases protein levels of the Hsp90-Cdc37 complex and the Hsp90-Cdc37 clients phosphorylated Akt and Cdk4 in A549 cells when used at a concentration of 5 μM. CAY10747 inhibits proliferation of A549, MCF-7, HOS, and HepG2 cells (IC50s = 0.41, 0.64, 0.9, and 0.94 μM, respectively) and induces apoptosis in A549 cells. 1.Li, N., Xu, M., Wang, B., et al.Discovery of novel celastrol derivatives as Hsp90-Cdc37 interaction disruptors with antitumor activityJ. Med. Chem.62(23)10798-10815(2019)

Aminohexylgeldanamycin (AHGDM), a derivative of Geldanamycin, is a highly effective inhibitor of HSP90. It exhibits considerable antiangiogenic and antitumor properties[1].

DP-1, a Ganetespib degradation product, represents a fragment derived from SDC-TRAP-0063. Ganetespib itself functions as an inhibitor of heat shock protein 90 (HSP90), exhibiting notable anti-tumor properties.

YZ129, a glioblastoma inhibitor, targets the HSP90-calcineurin-NFAT pathway by directly binding to heat shock protein 90 (HSP90) and exhibits an IC 50 of 820 nM on NFAT nuclear translocation. It induces cell-cycle arrest at the G2/M phase in GBM cells, leading to apoptosis and inhibiting tumor cell proliferation and migration [1].

Dimethyl-bisphenol A (DMBPA) is a potent inhibitor of HIF-1α, promoting its degradation by dissociating Hsp90 from HIF-1α and thus decreasing the expression of Vegfa mRNA [1].

HDAC6 HSP90-IN-2 (compound 6e) is a dual inhibitor of HDAC6 and Hsp90 with IC50 values of 105.7 nM and 61 nM, respectively, primarily used in cancer research [1].

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.

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.

HSP90-IN-19 is a potent inhibitor of heat shock protein 90 (Hsp90), exhibiting inhibitory activity with an IC50 of 0.27 μM. It is utilized in the research of viral infections, neurodegenerative diseases, and inflammation [1].

PROTAC HSP90 degrader BP3 potently and selectively degrades HSP90 through a CRBN-dependent mechanism. It effectively diminishes HSP90 protein levels in MCF-7 cells with a half-maximal degradation concentration (DC50) of 0.99 µM. Additionally, this compound impedes the proliferation of breast cancer cells [1].

PDK-IN-1 (compound 7o), a pyruvate dehydrogenase kinase (PDK) inhibitor, exhibits IC50 values of 0.03 and 0.1 μM against PDK1 and HSP90, respectively. This compound effectively targets the PDH PDK axis, significantly reducing tumor mass [1].

HEMTAC CDK4 6 degrader 1 is a PROTAC connected by ligands for HSP90 and CDK4 6 with a ( K_d ) value of 35.7 μM. It induces CDK4 6 degradation in B16F10 melanoma cells, arrests the cell cycle at the G0 G1 phase, and induces apoptosis. HEMTAC CDK4 6 degrader 1 can be used in cancer research [1].

Anticancer agent 136 (compound 22), a C17-triazole analogue of Geldanamycin (GDM), exhibits an IC50 value of 3.38 μM against human dermal fibroblasts (HDF) and binds to Heat shock protein 90 (Hsp90) with a dissociation constant (Kd) of 3.86 μM, demonstrating its apoptosis-inducing capabilities [1].

HSP90-IN-23 (Comp 12-1), a heat shock protein 90 (HSP90) inhibitor, exhibits potent activity with an IC50 of 9 nM, promotes apoptosis in tumor cells, and arrests their cell cycle at the G0 G1 phase, making it applicable for cancer research [1].

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].