Gamitrinib is a small molecule mitochondrial Hsp90 inhibitor, selectively targets Hsp90 network in tumor mitochondria; Gamitrinibs were shown to accumulate in the mitochondria of human tumor cell lines and to inhibit Hsp90 activity by acting as ATPase antagonists. Unlike Hsp90 antagonists not targeted to mitochondria, Gamitrinibs exhibited a "mitochondriotoxic" mechanism of action, causing rapid tumor cell death and inhibiting the growth of xenografted human tumor cell lines in mice. Gamitrinib were not toxic to normal cells or tissues and did not affect Hsp90 homeostasis in cellular compartments other than mitochondria.

HS-131 is an imaging probe of Hsp90 activity by linking it to a near-infrared (nIR) dye, HS131 uptake into cells correlated with cell membrane expression of Hsp90 and was used to image molecular subtypes of murine and human breast cancers in vitro and in murine models.

Hsp90 inhibitor 5b is a first-in-class, small molecule inhibitor of the C-terminal (CTD) Hsp90 dimerization with KD of 3.42 uM, IC50 of 1.3 uM against leukemia cell line K562.Hsp90 inhibitor 5b inhibits Hsp90 chaperone function, does not show any interaction with the NTD of Hsp90.Hsp90 inhibitor 5b down-regulated the phospho-BCR-ABL1 and total-BCR-ABL1 levels, as well as the related downstream signaling pathways, additionally reduced the expression of client proteins associated with Hsp90 chaperone activity, involving Akt, Stat5, and c-Myc.Hsp90 inhibitor 5b inhibited leukemic cell lines (K562, KCL22 and HL60) proliferation and induced apoptosis in a caspase 3/7 enzyme-dependent assay.Hsp90 inhibitor 5b is effective against resistant leukemia cells and in the zebrafish xenotransplantation model.

Hsp90α-IN-12h is the first Hsp90α-selective inhibitor with IC50 of 460 nM, exhibit 48-fold selectivity versus other Hsp90 isoforms.In NCI-H522 cells, Hsp90a-dependent substrates are readily degraded in the presence of Hsp90a-selective inhibitor.

KUNB 31 is a potent, isoform-selective Hsp90β inhibitor with Kd of 0.18 uM, displays 50-fold selectivity over Hsp90α and Grp94; exhibits anti-proliferative activity against NCI H23, UC3, and HT-29 cancer cell lines with IC50 of 6.74 µM, 3.01 µM, and 3.72 µM, respectively; specificly induces the degradation of Hsp90β-dependent client proteins (EGFR, HER2, CDK4, CDK6, CXCR4 etc.) in cells.

NPX-800 is a potent, selective, oral heat shock factor 1 (HSF1) pathway inhibitor.

S1g-2 (Hsp70-Bim inhibitor S1g-2) is a selective inhibitor to block interactions of Hsp70-Bim with IC50 of 0.4 uM in FPA assays, > 40-fold selectivity to target Hsp70-Bim over Bcl-2-Bim. S1g-2 induces cell-type-specific apoptosis in CML cells through selectively disrupting the Hsp70-Bim PPI. S1g-2 progressively enhanced lethality along with the increase in BCR-ABL-independent TKI resistance in the K562 cell lines. S1g-2 is more effective in primary samples from BCR-ABL-independent TKI-resistant patients than those from TKI-sensitive patients.

SEW84 (SEW04784) is a first-in-class, specific inhibitor of the Aha1-stimulated Hsp90 (ASH) ATPase activity (IC50=0.3 uM) without inhibiting basal Hsp90 ATPase; SEW84 binds to the C-terminal domain of Aha1 (Kd=1.7 uM) to weaken its asymmetric binding to Hsp90. SEW84 inhibited the GR- and AR-dependent luciferase expression with IC50 of 1.3 uM and 0.7 uM respectively. SEW84 blocks Aha1-dependent Hsp90 chaperoning activities, including the in vitro and in vivo refolding of firefly luciferase, and the transcriptional activity of the androgen receptor in cell-based models of prostate cancer. SEW84 promotes the clearance of phosphorylated tau in cellular and tissue models of neurodegenerative tauopathy.

SU086 is an inhibitor of HSP90, binds to HSP90-alpha and HSP90-beta isoforms, decreases HSP90 protein levels in prostate cancer cells.SU086 is a potent inhibitor of prostate cancer cell growth, migration, and invasion in vitro, significantly inhibited growth of AR-positive CRPC cell lines (C4-2), AR-negative (DU145 and PC-3) CRPC cells, and CRPC cells with expression of AR and AR splice variant, AR-V7 (22Rv1) (IC50 <10 uM).SU086 inhibits prostate cancer growth in preclinical models of prostate cancer in vivo.SU086 strongly enhances the anti-tumor activity of standard of care second-generation anti-androgens enzalutamide and abiraterone and inhibits prostate cancer cell growth in vitro and tumor growth in vivo.

EC144 is a potent and selective inhibitor of heat shock protein 90 (Hsp90) with an IC50 of 1.1 nM. EC144 inhibits tumor growth and causes partial tumor regressions. EC144 has the potential for the research of cancer diseases.

Macbecin is a stable HSP90 inhibitor by binding to the ATP-binding site with an IC50 of 2 μM and a Kd of 0.24 μM. Macbecin exhibits antitumor and cytocidal activities.

KU-177 is a potent inhibitor of Hsp90 ATPase homologue 1 (Aha1), ablates Aha1-driven enhancement of Hsp90-dependent tau aggregation. KU-177 also disrupts Aha1/Hsp90 interactions (IC50=4.08 μM) without inhibition of Hsp90’s ATPase activity. KU-177 can be used for tauopathies research.

A potent Hsp90 inhibitor with IC50 of 5 nM in cell-free assays.

BX-2819 is a potent, selective Hsp90 inhibitor with KD of 16.4 nM for human Hsp90α, also is a potent B. burgdorferi high-temperature protein G (Bb HtpG) with KD of 12 nM.

DCEM1 is a mitochondrial unfolded protein response (UPRmt) inhibitor, specifically disrupts HSP60-ClpP interaction in PCa cells and in vitro, suppresses prostate cancer growth in vivo.

Foldlin is a small-molecule tool compound that reduces the protein levels of misfolded/aggregated mutant p53, without effect on contact mutants or wild-type p53, Foldlin is small-molecule HSF-1 activator.

HLQ2H (Msi3 inhibitor 2H) is a first-in-class, specific inhibitor of fungal Hsp110 molecular chaperone Msi3, inhibits the holdase activity of Msi3 (IC50=5.02 uM) as well as the growth and viability of C. albicans.

KUNG65 is a potent, selective glucose regulated protein 94 (Grp94) inhibitor with Kd value of 540 nM in fluorescence polarization assays, 73-fold selectivity over Hsp90α.

PLIHZ is a small molecule inhibitor of DNAJA1 derived from the natural compound plumbagin, binds to J domain of DNAJA1 and efficiently reduces the levels of DNAJA1 and several conformational mutp53 with minimal impact on DNA contact mutp53 and wild-type p

PLTFBH is a cell-active small molecule inhibitor of DNAJA1, binds to and reduces protein levels of DNAJA1 and several other HSP40/J-domain proteins (JDPs), specifically reduces conformational mutp53 levels similar to PLIHZ.

SL-145 is a novel C-terminal HSP90 inhibitor, induces apoptosis in TNBC cells via the suppression of oncogenic AKT, MEK/ERK, and JAK2/STAT3 signaling.

SOMCL-16-175 is a non-covalent, allosteric modulator targeting Hsp90α’s middle domain (Hsp90M) with binding Kd of 804 uM, inhibits breast cancer cell growth and proliferation.