HSP90AB1

Summary

HSP90AB1 (heat shock protein 90 alpha family class B member 1, HGNC:5258) is a protein-coding gene on chromosome 6p21.1, encoding Heat shock protein HSP 90-beta (P08238). Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. It is a selective cancer dependency (DepMap: 10.8% of cell lines).

This gene encodes a member of the heat shock protein 90 family; these proteins are involved in signal transduction, protein folding and degradation and morphological evolution. This gene encodes the constitutive form of the cytosolic 90 kDa heat-shock protein and is thought to play a role in gastric apoptosis and inflammation. Alternative splicing results in multiple transcript variants. Pseudogenes have been identified on multiple chromosomes.

Source: NCBI Gene 3326 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 86 total
• Druggable target: yes — 21 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
• Cancer dependency (DepMap): dependent in 10.8% of screened cell lines
• MANE Select transcript: NM_007355

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5258
Approved symbol	HSP90AB1
Name	heat shock protein 90 alpha family class B member 1
Location	6p21.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000096384
Ensembl biotype	protein_coding
OMIM	140572
Entrez	3326

Gene structure

Transcript identifiers

Ensembl transcripts: 43 — 43 protein_coding

ENST00000353801, ENST00000371554, ENST00000371646, ENST00000620073, ENST00000874960, ENST00000874961, ENST00000874962, ENST00000874963, ENST00000874964, ENST00000874965, ENST00000874966, ENST00000874967, ENST00000874968, ENST00000924559, ENST00000924560, ENST00000924561, ENST00000924562, ENST00000924563, ENST00000924564, ENST00000924565, ENST00000924566, ENST00000924567, ENST00000924568, ENST00000924569, ENST00000924570, ENST00000924571, ENST00000924572, ENST00000924573, ENST00000924574, ENST00000924575, ENST00000924576, ENST00000924577, ENST00000924578, ENST00000924579, ENST00000945727, ENST00000945728, ENST00000945729, ENST00000945730, ENST00000945731, ENST00000945732, ENST00000945733, ENST00000945734, ENST00000945735

RefSeq mRNA: 6 — MANE Select: NM_007355 NM_001271969, NM_001271970, NM_001271971, NM_001271972, NM_001371238, NM_007355

CCDS: CCDS4909

Canonical transcript exons

ENST00000371646 — 12 exons

Exon	Start	End
ENSE00000974672	44251999	44252267
ENSE00000974673	44253045	44253378
ENSE00001140336	44251737	44251884
ENSE00001140344	44251418	44251608
ENSE00001427294	44253489	44253883
ENSE00002206271	44249675	44249834
ENSE00002445221	44249377	44249583
ENSE00002458977	44250291	44250599
ENSE00002502092	44251048	44251213
ENSE00003302626	44250021	44250154
ENSE00003758763	44248630	44248776
ENSE00003844715	44247101	44247195

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 99.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 1374.5451 / max 22047.1515, expressed in 1828 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
68003	1364.3940	1828
68009	4.6369	1442
68012	2.8757	1282
68010	1.2428	589
68006	0.3745	145
68005	0.2959	89
68000	0.2414	92
68002	0.1988	76
68004	0.1626	58
68008	0.0709	18

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
frontal pole	UBERON:0002795	99.92	gold quality
Brodmann (1909) area 10	UBERON:0013541	99.85	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.82	gold quality
paraflocculus	UBERON:0005351	99.82	gold quality
substantia nigra pars compacta	UBERON:0001965	99.80	gold quality
middle frontal gyrus	UBERON:0002702	99.80	gold quality
pons	UBERON:0000988	99.79	gold quality
tibialis anterior	UBERON:0001385	99.78	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.76	gold quality
dorsal root ganglion	UBERON:0000044	99.75	gold quality
islet of Langerhans	UBERON:0000006	99.73	gold quality
right frontal lobe	UBERON:0002810	99.73	gold quality
prefrontal cortex	UBERON:0000451	99.69	gold quality
cingulate cortex	UBERON:0003027	99.69	gold quality
cortical plate	UBERON:0005343	99.69	gold quality
anterior cingulate cortex	UBERON:0009835	99.69	gold quality
type B pancreatic cell	CL:0000169	99.68	gold quality
left ovary	UBERON:0002119	99.68	gold quality
superior vestibular nucleus	UBERON:0007227	99.68	gold quality
adrenal tissue	UBERON:0018303	99.68	gold quality
right uterine tube	UBERON:0001302	99.67	gold quality
pituitary gland	UBERON:0000007	99.66	gold quality
frontal cortex	UBERON:0001870	99.66	gold quality
cerebellar cortex	UBERON:0002129	99.66	gold quality
cerebellar hemisphere	UBERON:0002245	99.66	gold quality
cartilage tissue	UBERON:0002418	99.66	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	99.66	gold quality
embryo	UBERON:0000922	99.65	gold quality
right adrenal gland	UBERON:0001233	99.65	gold quality
adenohypophysis	UBERON:0002196	99.65	gold quality

Single-cell (SCXA)

Detected in 35 experiment(s), a significant marker in 16.

Experiment	Marker?	Max mean expression
E-MTAB-8410	yes	2994.63
E-MTAB-10042	yes	2924.72
E-MTAB-9801	yes	2758.69
E-HCAD-4	yes	1400.01
E-HCAD-35	yes	57.03
E-HCAD-1	yes	48.64
E-CURD-122	yes	45.84
E-CURD-88	yes	23.15
E-CURD-112	yes	19.82
E-MTAB-10553	yes	19.61
E-MTAB-9543	yes	18.75
E-MTAB-9221	yes	18.69
E-MTAB-7316	yes	15.56
E-GEOD-125970	yes	13.65
E-GEOD-130148	yes	11.35

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, CEBPD, DDIT3, HIF1A, HOPX, HSF1, KLF4, MYC, NFKB, RXRA, STAT3, TP53, VDR

miRNA regulators (miRDB)

18 targeting HSP90AB1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-10522-5P	99.26	68.50	2087
HSA-MIR-4801	98.96	69.42	2096
HSA-MIR-6827-5P	98.46	64.88	1256
HSA-MIR-6873-5P	98.45	66.14	1417
HSA-MIR-6810-5P	98.29	66.21	975
HSA-MIR-4457	98.09	67.12	1274
HSA-MIR-6893-3P	97.79	64.91	1238
HSA-MIR-939-5P	97.10	65.80	1579
HSA-MIR-370-3P	97.09	64.92	1221
HSA-MIR-1343-5P	96.48	66.06	1506

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 10.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• PKC-epsilon is specifically required in the signaling pathway leading to the induction of hsp90 beta gene in response to heat shock. (PMID:14532285)
• hsp90beta is repressed by p53 in UV irradiation-induced apoptosis (PMID:15284248)
• Mutations at the phosphorylation sites of HSP90-beta modulate the interaction with arylhydrocarbon receptor (AhR) and may negatively regulate formation of the functional AhR complex in the steady-state cytosol. (PMID:15581363)
• The overexpression of HSP70 and HSP90beta are probably correlated with the occurrence, development and prognosis of nasopharyngeal carcinoma. (PMID:16248461)
• JAK1/2 are client proteins of Hsp90 alpha and beta; Hsp90 and CDC37 play a critical role in types I and II interferon pathways (PMID:16280321)
• Hydrogen-exchange mass spectrometry was used to study structural & conformational changes undergone by full-length Hsp90beta in solution upon binding of the co-chaperone Cdc37 & 2 Hsp90 ATPase inhibitors: Radicicol & the anticancer drug DMAG (PMID:17764690)
• Results suggest that HSP90 beta prevents auto-ubiquitination and degradation of its client protein c-IAP1, whose depletion would be sufficient to inhibit cell differentiation. (PMID:18239673)
• GCUNC45 is required for the normal cellular distribution of Hsp90beta, but not Hsp90alpha. (PMID:18285346)
• The conversion of Thr(566) and Ala(629) of Hsp90alpha to Ala(558) and Met(621) is primarily responsible for impeded dimerization of Hsp90beta. (PMID:18347946)
• conformational analysis of hydrolysis by human Hsp90alpha and Hsp90beta (PMID:18400751)
• Tah1 is specific for Hsp90, and is able to bind tightly the yeast Hsp90, and the human Hsp90alpha and Hsp90beta proteins, but not the yeast Hsp70 Ssa1 isoform (PMID:18412542)
• These data provide an explanation for apoptosome inhibition by activated leukemogenic tyrosine kinases and suggest that alterations in Hsp90beta-apoptosome interactions may contribute to chemoresistance in leukemias. (PMID:18591256)
• Presence of ovarian autoantibodies to human HSP90 in sera of women with infertility could be involved in human ovarian autoimmunity and thereby be a causative factor in early ovarian failure. (PMID:19022436)
• Hsp90 overexpression correlates with several adverse parameters for gastrointestinal stromal tumors. Hsp90alpha seems more relevant to the aggressiveness of gastrointestinal stromal tumors than Hsp90beta (PMID:19047110)
• Study points to a potential role for Hsp90beta in MSC biology. (PMID:19327008)
• Results show that heat shock protein 90 beta is cleaved by activated caspase-10 under UVB irradiation. (PMID:19380486)
• Expression profiling of Hsp90alpha and Hsp90beta and its cochaperone proteins may be useful for cancer diagnosis and prognosis. (PMID:19576239)
• COMMD1 has a role in conjunction with HSP90beta/HSP70 in the ubiquitin and O(2)-independent regulation of HIF-1alpha (PMID:19802386)
• celastrol may represent a new class of Hsp90 inhibitor by modifying Hsp90 C terminus to allosterically regulate its chaperone activity and disrupt Hsp90-Cdc37 complex. (PMID:19858214)
• Data show that the small molecule celastrol inhibits the Hsp90 chaperoning machinery by inactivating the co-chaperone p23, resulting in a more selective destabilization of steroid receptors. (PMID:19996313)
• findings present novel Hsp90 mutants that render cells resistant to Hsp90 inhibitors; show that the resistance depends on the increased ATPase turnover due to enhanced interaction with Aha1 (PMID:20226818)
• H. pylori induces the translocation of HSP90beta from the cytosol to the membrane and interaction of HSP90beta and Rac1, which leads to the activation of NADPH oxidase and production of ROS in gastric epithelial cells. (PMID:20451655)
• Results show that RPL4, RPLP0, and HSPCB were the most stable reference genes in ovarian tissues. (PMID:20705598)
• cyclophilin A and Hsp90 facilitate translocation of lethal factor(N) diphtheria toxin, but not of lethal factor, across endosomal membranes, and thus they function selectively in promoting translocation of certain proteins, but not of others (PMID:20946244)
• a possible role for HSP90AB1 in postentry HIV replication and may provide an attractive target for therapeutic intervention. (PMID:21602280)
• TRIM8 modulates translocation of phosphorylated STAT3 into the nucleus through interaction with Hsp90beta and consequently regulates transcription of Nanog in embryonic stem cells. (PMID:21689689)
• Data identify HSP90 as a pro-inflammatory molecule in retinal pigmented epithelial cell sterile inflammatory responses. (PMID:22019372)
• DNA sequencing of 101 human samples detects eight and seven unique single nucleotide polymorphisms (SNPs) at the HSP90AA1 and HSP90AB1 loci, respectively. (PMID:22185817)
• Using a proteomic analysis, we determined that the cleavage occurs in a conserved motif of the N-terminal nucleotide binding site, between Ile-126 and Gly-127 in Hsp90beta, and between Ile-131 and Gly-132 in Hsp90alpha. (PMID:22848402)
• results demonstrate that Hsp90 plays an essential role in regulating PTK6 stability and suggest that Hsp90 inhibitors may be useful as therapeutic drugs for PTK6-positive cancers, including breast cancer (PMID:22849407)
• The upregulation of Hsp90-beta was associated with poor post-surgical survival time and lymphatic metastasis of lung cancer patients (PMID:22929401)
• the transdominant effect of HSP90AB1 on capsid-spacer protein 1-mutant HIV infectivity suggests a potential role for this class of cellular chaperones in HIV core stability and uncoating. (PMID:23200770)
• HSP90beta may positively regulate angiogenesis, not only as a protein chaperone, but also as an mRNA stabilizer for pro-angiogenic genes, such as BAZF, in a PRKD2 activity-dependent manner. (PMID:23515950)
• differences in expression caused by the -144 polymorphism in the HSP90beta promoter are associated with cellular inflammatory responses and the severity of organ injury (PMID:23516526)
• Hsp90 is upregulated in systemic sclerosis (SSc) and is critical for TGF-beta signalling. (PMID:23661493)
• Here we describe the specific association of heat shock protein-90-beta (Hsp90beta) with EV71 viral particles by the co-purification with virions using sucrose density gradient ultracentrifugation and colocalization as shown by immunogold EM. (PMID:23711381)
• CDC37 has an important role in chaperoning protein kinases; it stabilizes kinase clients by a mechanism that is not dependent on a substantial direct interaction between CDC37 and HSP90, but requires HSP90 activity (PMID:24292678)
• Hsp90 binds directly to fibronectin (FN) and inhibition reduces the extracellular fibronectin matrix in breast cancer cells. (PMID:24466266)
• The frequency of mutant CC genotype for HSP90AA1 (rs4947C/T), mutant AA genotype for HSP90AB1 (rs13296A/G) and mutant CC genotype for HSP90B1 (rs2070908 C/G) was significantly higher in the patient group than in controls. (PMID:24511009)
• Study obtained a structural model of Hsp90 in complex with its natural disease-associated substrate, the intrinsically disordered Tau protein. Hsp90 binds to a broad region in Tau that includes the aggregation-prone repeats. (PMID:24581495)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	hsp90ab1	ENSDARG00000029150
mus_musculus	Hsp90ab1	ENSMUSG00000023944
rattus_norvegicus	Hsp90ab1	ENSRNOG00000019834
drosophila_melanogaster	Hsp83	FBGN0001233
caenorhabditis_elegans		WBGENE00000915

Paralogs (3): HSP90AA1 (ENSG00000080824), TRAP1 (ENSG00000126602), HSP90B1 (ENSG00000166598)

Protein

Protein identifiers

Heat shock protein HSP 90-beta — P08238 (reviewed: P08238)

Alternative names: Heat shock 84 kDa, Heat shock protein family C member 3

All UniProt accessions (1): P08238

UniProt curated annotations — full annotation on UniProt →

Function. Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function. Engages with a range of client protein classes via its interaction with various co-chaperone proteins or complexes, that act as adapters, simultaneously able to interact with the specific client and the central chaperone itself. Recruitment of ATP and co-chaperone followed by client protein forms a functional chaperone. After the completion of the chaperoning process, properly folded client protein and co-chaperone leave HSP90 in an ADP-bound partially open conformation and finally, ADP is released from HSP90 which acquires an open conformation for the next cycle. Apart from its chaperone activity, it also plays a role in the regulation of the transcription machinery. HSP90 and its co-chaperones modulate transcription at least at three different levels. They first alter the steady-state levels of certain transcription factors in response to various physiological cues. Second, they modulate the activity of certain epigenetic modifiers, such as histone deacetylases or DNA methyl transferases, and thereby respond to the change in the environment. Third, they participate in the eviction of histones from the promoter region of certain genes and thereby turn on gene expression. Antagonizes STUB1-mediated inhibition of TGF-beta signaling via inhibition of STUB1-mediated SMAD3 ubiquitination and degradation. Promotes cell differentiation by chaperoning BIRC2 and thereby protecting from auto-ubiquitination and degradation by the proteasomal machinery. Main chaperone involved in the phosphorylation/activation of the STAT1 by chaperoning both JAK2 and PRKCE under heat shock and in turn, activates its own transcription. Involved in the translocation into ERGIC (endoplasmic reticulum-Golgi intermediate compartment) of leaderless cargos (lacking the secretion signal sequence) such as the interleukin 1/IL-1; the translocation process is mediated by the cargo receptor TMED10. (Microbial infection) Binding to N.meningitidis NadA stimulates monocytes. Seems to interfere with N.meningitidis NadA-mediated invasion of human cells.

Subunit / interactions. Monomer. Homodimer. Forms a complex with CDK6 and CDC37. Interacts with UNC45A; binding to UNC45A involves 2 UNC45A monomers per HSP90AB1 dimer. Interacts with CHORDC1. Interacts with DNAJC7. Interacts with FKBP4. May interact with NWD1. Interacts with SGTA. Interacts with HSF1 in an ATP-dependent manner. Interacts with MET; the interaction suppresses MET kinase activity. Interacts with ERBB2 in an ATP-dependent manner; the interaction suppresses ERBB2 kinase activity. Interacts with HIF1A, KEAP1 and RHOBTB2. Interacts with STUB1 and SMAD3. Interacts with XPO1 and AHSA1. Interacts with BIRC2. Interacts with KCNQ4; promotes cell surface expression of KCNQ4. Interacts with BIRC2; prevents auto-ubiquitination and degradation of its client protein BIRC2. Interacts with NOS3. Interacts with AHR; interaction is inhibited by HSP90AB1 phosphorylation on Ser-226 and Ser-255. Interacts with STIP1 and CDC37; upon SMYD2-dependent methylation. Interacts with JAK2 and PRKCE; promotes functional activation in a heat shock-dependent manner. Interacts with HSP90AA1; interaction is constitutive. HSP90AB1-CDC37 chaperone complex interacts with inactive MAPK7 (via N-terminal half) in resting cells; the interaction is MAP2K5-independent and prevents from ubiquitination and proteasomal degradation. Interacts with CDC25A; prevents heat shock-mediated CDC25A degradation and contributes to cell cycle progression. Interacts with TP53 (via DNA binding domain); suppresses TP53 aggregation and prevents from irreversible thermal inactivation. Interacts with TGFB1 processed form (LAP); inhibits latent TGFB1 activation. Interacts with TRIM8; prevents nucleus translocation of phosphorylated STAT3 and HSP90AB1. Interacts with NR3C1 (via domain NR LBD) and NR1D1 (via domain NR LBD). Interacts with PDCL3. Interacts with TTC4 (via TPR repeats). Interacts with IL1B; the interaction facilitates cargo translocation into the ERGIC. (Microbial infection) Protein on the cell surface interacts with N.meningitidis serogroup B adhesin A (nadA).

Subcellular location. Cytoplasm. Melanosome. Nucleus. Secreted. Cell membrane. Dynein axonemal particle. Cell surface.

Post-translational modifications. Ubiquitinated in the presence of STUB1-UBE2D1 complex (in vitro). ISGylated. S-nitrosylated; negatively regulates the ATPase activity. Phosphorylation at Tyr-301 by SRC is induced by lipopolysaccharide. Phosphorylation at Ser-226 and Ser-255 inhibits AHR interaction. Methylated by SMYD2; facilitates dimerization and chaperone complex formation; promotes cancer cell proliferation. Cleaved following oxidative stress resulting in HSP90AB1 protein radicals formation; disrupts the chaperoning function and the degradation of its client proteins.

Activity regulation. In the resting state, through the dimerization of its C-terminal domain, HSP90 forms a homodimer which is defined as the open conformation. Upon ATP-binding, the N-terminal domain undergoes significant conformational changes and comes in contact to form an active closed conformation. After HSP90 finishes its chaperoning tasks of assisting the proper folding, stabilization and activation of client proteins under the active state, ATP molecule is hydrolyzed to ADP which then dissociates from HSP90 and directs the protein back to the resting state.

Domain organisation. The TPR repeat-binding motif mediates interaction with TPR repeat-containing proteins.

Induction. By heat shock.

Similarity. Belongs to the heat shock protein 90 family.

RefSeq proteins (6): NP_001258898, NP_001258899, NP_001258900, NP_001258901, NP_001358167, NP_031381* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001404	Hsp90_fam	Family
IPR003594	HATPase_dom	Domain
IPR019805	Heat_shock_protein_90_CS	Conserved_site
IPR020568	Ribosomal_Su5_D2-typ_SF	Homologous_superfamily
IPR020575	Hsp90_N	Domain
IPR036890	HATPase_C_sf	Homologous_superfamily
IPR037196	HSP90_C	Homologous_superfamily

Pfam: PF00183, PF13589

Enzyme classification (BRENDA):

• EC 3.6.4.10 — non-chaperonin molecular chaperone ATPase (BRENDA: 16 organisms, 6 substrates, 0 inhibitors, 0 Km, 0 kcat entries)

UniProt features (125 total): strand 33, helix 30, modified residue 22, mutagenesis site 10, region of interest 8, turn 6, binding site 5, sequence conflict 3, glycosylation site 2, initiator methionine 1, chain 1, short sequence motif 1, compositionally biased region 1, site 1, sequence variant 1

Structure

Experimental structures (PDB)

32 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
9D9I	X-RAY DIFFRACTION	1.5
6N8Y	X-RAY DIFFRACTION	1.55
5UCJ	X-RAY DIFFRACTION	1.69
7ULJ	X-RAY DIFFRACTION	1.82
9D9H	X-RAY DIFFRACTION	1.96
5UC4	X-RAY DIFFRACTION	2.05
3FWV	X-RAY DIFFRACTION	2.2
3NMQ	X-RAY DIFFRACTION	2.2
3PRY	X-RAY DIFFRACTION	2.28
1UYM	X-RAY DIFFRACTION	2.45
3UQ3	X-RAY DIFFRACTION	2.6
9W5I	ELECTRON MICROSCOPY	2.63
5UCH	X-RAY DIFFRACTION	2.65
5UCI	X-RAY DIFFRACTION	2.7
8QMO	ELECTRON MICROSCOPY	2.76
7ZUB	ELECTRON MICROSCOPY	2.85
1QZ2	X-RAY DIFFRACTION	3
6N8W	X-RAY DIFFRACTION	3.09
8EOB	ELECTRON MICROSCOPY	3.1
7Z38	ELECTRON MICROSCOPY	3.16
8GAE	ELECTRON MICROSCOPY	3.3
7ZR0	ELECTRON MICROSCOPY	3.4
7Z37	ELECTRON MICROSCOPY	3.67
8GFT	ELECTRON MICROSCOPY	3.8
5FWK	ELECTRON MICROSCOPY	3.9
7ZR5	ELECTRON MICROSCOPY	3.9
8EOA	ELECTRON MICROSCOPY	3.9
7ZR6	ELECTRON MICROSCOPY	4.2
5FWP	ELECTRON MICROSCOPY	7.2
5FWM	ELECTRON MICROSCOPY	8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P08238-F1	84.68	0.57

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 126–127 (cleaved under oxidative stress)

Ligand- & substrate-binding residues (5): 46; 88; 107; 133; 392

Post-translational modifications (22): 219, 226, 255, 261, 297, 301, 305, 307, 399, 435, 445, 479, 481, 484, 531, 531, 574, 577, 590, 624 …

Glycosylation sites (2): 434, 452

Mutagenesis-validated functional residues (10):

Position	Phenotype
42	strong atp-binding. strong interaction with hsf1, hif1a, erbb2, met, keap1 and rhobtb2.
88	impaired atp-binding. strong interaction with hif1a, met, keap1 and rhobtb2. loss of interaction with hsf1 and erbb2.
226	increases the binding affinity for ahr; when associated with a-255. increases ahr transcription activity; when associate
226	no effect on the interaction with ahr; when associated with e-255.
255	increases the binding affinity for ahr; when associated with a-226. increases ahr transcription activity; when associate
255	no effect on the interaction with ahr; when associated with e-226.
301	decreases interaction with nos3 and src. impairs resists lps-induced tyrosine phosphorylation. does not block lps-induce
531	highly decreases the signal of smyd2-dependent hsp90ab1 methylation; when associated with a-574. diminishes dimerized fo
574	decreases the signal of smyd2-dependent hsp90ab1 methylation. highly decreases the signal of smyd2-dependent hsp90ab1 me
590	reduced atpase activity and client protein activation.

Function

Pathways and Gene Ontology

Reactome pathways

22 pathways

ID	Pathway
R-HSA-168928	DDX58/IFIH1-mediated induction of interferon-alpha/beta
R-HSA-2029482	Regulation of actin dynamics for phagocytic cup formation
R-HSA-3371497	HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand
R-HSA-3371511	HSF1 activation
R-HSA-3371568	Attenuation phase
R-HSA-3371571	HSF1-dependent transactivation
R-HSA-399954	Sema3A PAK dependent Axon repulsion
R-HSA-5336415	Uptake and function of diphtheria toxin
R-HSA-6798695	Neutrophil degranulation
R-HSA-844456	The NLRP3 inflammasome
R-HSA-8852276	The role of GTSE1 in G2/M progression after G2 checkpoint
R-HSA-8937144	Aryl hydrocarbon receptor signalling
R-HSA-8939211	ESR-mediated signaling
R-HSA-9013418	RHOBTB2 GTPase cycle
R-HSA-9018519	Estrogen-dependent gene expression
R-HSA-9613829	Chaperone Mediated Autophagy
R-HSA-9660826	Purinergic signaling in leishmaniasis infection
R-HSA-9679191	Potential therapeutics for SARS
R-HSA-9705671	SARS-CoV-2 activates/modulates innate and adaptive immune responses
R-HSA-9820962	Assembly and release of respiratory syncytial virus (RSV) virions
R-HSA-9834752	Respiratory syncytial virus genome replication
R-HSA-9920588	Dengue virus activates/modulates innate and adaptive immune responses

MSigDB gene sets: 510 (showing top): REACTOME_DDX58_IFIH1_MEDIATED_INDUCTION_OF_INTERFERON_ALPHA_BETA, ATF_B, GOBP_RNA_TEMPLATED_DNA_BIOSYNTHETIC_PROCESS, WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, RNGTGGGC_UNKNOWN, GOBP_CHROMOSOME_ORGANIZATION, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, REACTOME_BIOLOGICAL_OXIDATIONS, GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, SHIPP_DLBCL_VS_FOLLICULAR_LYMPHOMA_UP, WWTAAGGC_UNKNOWN, GOBP_RESPONSE_TO_INTERLEUKIN_4

GO Biological Process (21): placenta development (GO:0001890), protein folding (GO:0006457), response to unfolded protein (GO:0006986), telomere maintenance via telomerase (GO:0007004), virion attachment to host cell (GO:0019062), positive regulation of transforming growth factor beta receptor signaling pathway (GO:0030511), regulation of protein ubiquitination (GO:0031396), negative regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032435), regulation of protein localization (GO:0032880), cellular response to heat (GO:0034605), negative regulation of apoptotic process (GO:0043066), positive regulation of nitric oxide biosynthetic process (GO:0045429), positive regulation of cell differentiation (GO:0045597), protein stabilization (GO:0050821), chaperone-mediated protein complex assembly (GO:0051131), regulation of cell cycle (GO:0051726), cellular response to interleukin-4 (GO:0071353), supramolecular fiber organization (GO:0097435), negative regulation of proteasomal protein catabolic process (GO:1901799), telomerase holoenzyme complex assembly (GO:1905323), positive regulation of protein localization to cell surface (GO:2000010)

GO Molecular Function (30): RNA binding (GO:0003723), double-stranded RNA binding (GO:0003725), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), protein kinase regulator activity (GO:0019887), kinase binding (GO:0019900), protein kinase binding (GO:0019901), MHC class II protein complex binding (GO:0023026), nitric-oxide synthase regulator activity (GO:0030235), TPR domain binding (GO:0030911), heat shock protein binding (GO:0031072), ubiquitin protein ligase binding (GO:0031625), peptide binding (GO:0042277), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), histone deacetylase binding (GO:0042826), ATP-dependent protein binding (GO:0043008), protein folding chaperone (GO:0044183), cadherin binding (GO:0045296), protein dimerization activity (GO:0046983), tau protein binding (GO:0048156), obsolete unfolded protein binding (GO:0051082), DNA polymerase binding (GO:0070182), protein phosphatase activator activity (GO:0072542), disordered domain specific binding (GO:0097718), ATP-dependent protein folding chaperone (GO:0140662), receptor ligand inhibitor activity (GO:0141069), histone methyltransferase binding (GO:1990226), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (23): extracellular region (GO:0005576), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytosol (GO:0005829), plasma membrane (GO:0005886), cell surface (GO:0009986), membrane (GO:0016020), protein-containing complex (GO:0032991), aryl hydrocarbon receptor complex (GO:0034751), secretory granule lumen (GO:0034774), melanosome (GO:0042470), neuronal cell body (GO:0043025), dendritic growth cone (GO:0044294), axonal growth cone (GO:0044295), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), protein folding chaperone complex (GO:0101031), dynein axonemal particle (GO:0120293), ficolin-1-rich granule lumen (GO:1904813), HSP90-CDC37 chaperone complex (GO:1990565), COP9 signalosome (GO:0008180)

Reactome top-level categories

Rollup of top-18 pathways:

Category	Pathways
Innate Immune System	2
Cellular response to heat stress	2
Fcgamma receptor (FCGR) dependent phagocytosis	1
Cellular responses to stress	1
HSF1-dependent transactivation	1
Semaphorin interactions	1
Uptake and actions of bacterial toxins	1
Inflammasomes	1
G2/M Transition	1
Phase I - Functionalization of compounds	1
Signaling by Nuclear Receptors	1
RHOBTB GTPase Cycle	1
ESR-mediated signaling	1
Autophagy	1
Cell recruitment (pro-inflammatory response)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	7
protein binding	4
cytoplasm	4
enzyme binding	2
intracellular membrane-bounded organelle	2
intracellular protein-containing complex	2
growth cone	2
animal organ development	1
cellular process	1
protein maturation	1
response to topologically incorrect protein	1
telomerase activity	1
RNA-templated DNA biosynthetic process	1
telomere maintenance via telomere lengthening	1
telomere-telomerase complex assembly	1
viral life cycle	1
adhesion of symbiont to host cell	1
virion binding	1
host cell surface binding	1
transforming growth factor beta receptor signaling pathway	1
regulation of transforming growth factor beta receptor signaling pathway	1
positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
positive regulation of cellular response to transforming growth factor beta stimulus	1
protein ubiquitination	1
regulation of protein modification by small protein conjugation or removal	1
regulation of proteasomal ubiquitin-dependent protein catabolic process	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
negative regulation of proteasomal protein catabolic process	1
negative regulation of ubiquitin-dependent protein catabolic process	1
intracellular protein localization	1
regulation of localization	1
response to heat	1
cellular response to stress	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
nitric oxide biosynthetic process	1
positive regulation of biosynthetic process	1
regulation of nitric oxide biosynthetic process	1
cell differentiation	1

Protein interactions and networks

STRING

10072 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HSP90AB1	DNAJB1	P25685	999
HSP90AB1	HSPA4	P34932	999
HSP90AB1	HSPA8	P11142	999
HSP90AB1	FKBP4	Q02790	998
HSP90AB1	CDC37	Q16543	998
HSP90AB1	STUB1	Q9UNE7	997
HSP90AB1	PPID	Q08752	997
HSP90AB1	STIP1	P31948	997
HSP90AB1	TOMM70	O94826	996
HSP90AB1	AKT1	P31749	996
HSP90AB1	AHSA1	O95433	995
HSP90AB1	AIP	O00170	995
HSP90AB1	FKBP5	Q13451	995
HSP90AB1	ST13	P50502	994
HSP90AB1	NR3C1	P04150	994
HSP90AB1	TP53	P04637	994

IntAct

1169 interactions, top by confidence:

A	B	Type	Score
IKBKG	IKBKB	psi-mi:“MI:0914”(association)	0.980
MAP3K14	CHUK	psi-mi:“MI:0914”(association)	0.950
CDC37	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.930
PPP5C	HSP90AB1	psi-mi:“MI:0407”(direct interaction)	0.900
FKBP5	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.890
HSP90AB1	FKBP5	psi-mi:“MI:0407”(direct interaction)	0.890
EGFR	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.890
HSP90AB1	MAPT	psi-mi:“MI:0407”(direct interaction)	0.880
HSP90AB1	MAPT	psi-mi:“MI:0915”(physical association)	0.880
HSP90AB1	CDC37L1	psi-mi:“MI:0915”(physical association)	0.850
CDC37L1	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.850

BioGRID (1628): HSP90AB1 (Reconstituted Complex), HSP90AB1 (Reconstituted Complex), HSP90AB1 (Affinity Capture-Western), HSP90AB1 (Affinity Capture-MS), HSP90AB1 (Affinity Capture-MS), CDC37L1 (Two-hybrid), HSP90AB1 (Affinity Capture-RNA), HSP90AB1 (Affinity Capture-MS), HSP90AB1 (Affinity Capture-MS), HSP90AB1 (Affinity Capture-MS), HSP90AB1 (Affinity Capture-MS), HSP90AB1 (Two-hybrid), HSP90AB1 (Reconstituted Complex), HSP90AB1 (Affinity Capture-MS), HSP90AB1 (Affinity Capture-MS)

ESM2 similar proteins: A2YWQ1, A5A6K9, O02192, O02705, O03986, O43109, O44001, O57521, O61998, P02828, P02829, P04809, P07900, P07901, P08238, P11499, P11501, P15108, P24724, P27323, P30946, P30947, P34058, P36181, P40292, P41887, P51818, P51819, P54651, P55737, P82995, Q04619, Q07078, Q08277, Q0J4P2, Q18688, Q4R4P1, Q4R4T5, Q4UDU8, Q5R710

Diamond homologs: A0KL53, A1ANS1, A1WXE4, A2YWQ1, A3QF50, A4SLY0, A5A6K9, A5GER7, B0TP05, F4JFN3, O02192, O02705, O03986, O18750, O43109, O44001, O57521, O61998, P02828, P02829, P04809, P04810, P04811, P06660, P07900, P07901, P08110, P08113, P08238, P11499, P11501, P12861, P14625, P15108, P24724, P27323, P27741, P27890, P30946, P30947

SIGNOR signaling

16 interactions.

A	Effect	B	Mechanism
SRC	up-regulates	HSP90AB1	phosphorylation
CSNK2A1	down-regulates	HSP90AB1	phosphorylation
luminespib	down-regulates	HSP90AB1	“chemical inhibition”
NVP-BEP800	down-regulates	HSP90AB1	“chemical inhibition”
HSP90AB1	“up-regulates activity”	AR	binding
AHSA1	“up-regulates activity”	HSP90AB1	binding
HSP90AB1	“up-regulates activity”	NOS3	binding
HSP90AB1	“up-regulates quantity by stabilization”	NOD2	binding
STIP1	“down-regulates activity”	HSP90AB1	binding
FNIP1	“down-regulates activity”	HSP90AB1	binding
FNIP2	“down-regulates activity”	HSP90AB1	binding
HSP90AB1	“up-regulates quantity by stabilization”	FLCN	binding
HSP90AB1	“up-regulates quantity”	CBLL1	binding
HSP90AB1	down-regulates	APAF1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 192 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
MAP3K8 (TPL2)-dependent MAPK1/3 activation	5	25.5×	4e-05
Signaling by ERBB2	8	19.8×	1e-06
Downregulation of ERBB2 signaling	7	19.0×	6e-06
Estrogen-dependent nuclear events downstream of ESR-membrane signaling	6	18.8×	3e-05
Attenuation phase	6	17.5×	4e-05
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	12	16.6×	5e-09
Signaling by high-kinase activity BRAF mutants	7	15.9×	2e-05
Signaling by RAS mutants	5	15.1×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
regulation of protein ubiquitination	5	26.7×	2e-04
positive regulation of peptidyl-serine phosphorylation	5	23.1×	3e-04
telomere maintenance via telomerase	5	22.1×	3e-04
protein refolding	5	18.8×	6e-04
positive regulation of telomere maintenance	6	18.5×	1e-04
intrinsic apoptotic signaling pathway	7	15.1×	9e-05
insulin-like growth factor receptor signaling pathway	5	14.9×	2e-03
regulation of signal transduction by p53 class mediator	6	13.8×	5e-04

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — MEL.

Clinical variants and AI predictions

ClinVar

86 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	51
Likely benign	2
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

1611 predictions. Top by Δscore:

Variant	Effect	Δscore
6:44248624:TTTTA:T	acceptor_loss	1.0000
6:44248625:TTTAG:T	acceptor_loss	1.0000
6:44248627:TA:T	acceptor_loss	1.0000
6:44248752:G:GT	donor_gain	1.0000
6:44248774:GAT:G	donor_gain	1.0000
6:44248775:AT:A	donor_gain	1.0000
6:44248777:G:GG	donor_gain	1.0000
6:44249372:TCCA:T	acceptor_loss	1.0000
6:44249374:CA:C	acceptor_loss	1.0000
6:44249375:A:AG	acceptor_gain	1.0000
6:44249375:A:AT	acceptor_loss	1.0000
6:44249375:AG:A	acceptor_gain	1.0000
6:44249376:G:GG	acceptor_gain	1.0000
6:44249376:GG:G	acceptor_gain	1.0000
6:44249470:G:GT	donor_gain	1.0000
6:44249471:A:T	donor_gain	1.0000
6:44249580:TCAG:T	donor_loss	1.0000
6:44249581:CAG:C	donor_loss	1.0000
6:44249582:AGGTA:A	donor_loss	1.0000
6:44249583:GGTAT:G	donor_loss	1.0000
6:44249592:GTTCT:G	donor_gain	1.0000
6:44249669:T:A	acceptor_gain	1.0000
6:44249673:A:AG	acceptor_gain	1.0000
6:44249673:AG:A	acceptor_gain	1.0000
6:44249673:AGGCT:A	acceptor_gain	1.0000
6:44249674:G:GG	acceptor_gain	1.0000
6:44249674:GG:G	acceptor_gain	1.0000
6:44249674:GGC:G	acceptor_gain	1.0000
6:44249674:GGCT:G	acceptor_gain	1.0000
6:44249674:GGCTG:G	acceptor_gain	1.0000

AlphaMissense

4846 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:44248678:T:A	F17I	1.000
6:44248678:T:C	F17L	1.000
6:44248678:T:G	F17V	1.000
6:44248679:T:C	F17S	1.000
6:44248679:T:G	F17C	1.000
6:44248680:T:A	F17L	1.000
6:44248680:T:G	F17L	1.000
6:44248700:T:A	L24H	1.000
6:44248700:T:C	L24P	1.000
6:44248709:T:A	L27H	1.000
6:44248709:T:C	L27P	1.000
6:44248712:T:A	I28N	1.000
6:44248726:T:C	Y33H	1.000
6:44248753:G:A	E42K	1.000
6:44248754:A:C	E42A	1.000
6:44248754:A:T	E42V	1.000
6:44248755:G:C	E42D	1.000
6:44248755:G:T	E42D	1.000
6:44248762:T:C	S45P	1.000
6:44248763:C:A	S45Y	1.000
6:44248763:C:T	S45F	1.000
6:44248767:T:A	N46K	1.000
6:44248767:T:G	N46K	1.000
6:44248774:G:C	D49H	1.000
6:44248774:G:T	D49Y	1.000
6:44248775:A:C	D49A	1.000
6:44248775:A:G	D49G	1.000
6:44248775:A:T	D49V	1.000
6:44248776:T:A	D49E	1.000
6:44248776:T:G	D49E	1.000

dbSNP variants (sampled 300 via entrez): RS1000003153 (6:44247997 T>G), RS1000114763 (6:44246423 G>A,C), RS1000200257 (6:44252487 A>G,T), RS1000491090 (6:44247757 A>G), RS1000530158 (6:44247353 T>G), RS1000752045 (6:44246512 C>T), RS1000787411 (6:44252342 A>G,T), RS1001629813 (6:44254364 G>A,C), RS1001670286 (6:44246561 C>G,T), RS1002037373 (6:44246684 G>A), RS1002516576 (6:44246472 TGCC>T,TGCCGCC), RS1002895654 (6:44253420 A>G), RS1002986585 (6:44245099 C>T), RS1003284285 (6:44247312 C>A,G,T), RS1004177795 (6:44252495 C>T)

Disease associations

OMIM: gene MIM:140572 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST005956_58	Waist-to-hip ratio adjusted for BMI	7.000000e-26
GCST005958_2	Waist-to-hip ratio adjusted for BMI (age >50)	2.000000e-19
GCST005962_2	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	3.000000e-31
GCST90002392_683	Mean corpuscular volume	3.000000e-24
GCST90002396_324	Mean reticulocyte volume	9.000000e-32
GCST90002403_163	Red blood cell count	4.000000e-12
GCST90002405_197	Reticulocyte count	2.000000e-10

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0010701	mean reticulocyte volume
EFO:0004305	erythrocyte count
EFO:0007986	reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (7): CHEMBL2095165 (PROTEIN FAMILY), CHEMBL3137265 (SELECTIVITY GROUP), CHEMBL4296081 (PROTEIN COMPLEX), CHEMBL4303 (SINGLE PROTEIN), CHEMBL6066030 (PROTEIN-PROTEIN INTERACTION), CHEMBL6193786 (PROTEIN-PROTEIN INTERACTION), CHEMBL6193787 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

21 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 610,821 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1440	TETRACYCLINE	4	324,384
CHEMBL1563	DAUNORUBICIN HYDROCHLORIDE	4	28,670
CHEMBL359744	DOXORUBICIN HYDROCHLORIDE	4	141,917
CHEMBL36506	NOVOBIOCIN	4	11,401
CHEMBL932	DIPYRIDAMOLE	4	51,743
CHEMBL109480	TANESPIMYCIN	3	3,645
CHEMBL1972860	ELESCLOMOL	3	774
CHEMBL2103879	GANETESPIB	3	2,075
CHEMBL377559	RETASPIMYCIN HYDROCHLORIDE	3	141
CHEMBL41286	DIACEREIN	3	5,090
CHEMBL1214827	ONALESPIB	2	878
CHEMBL1229908	ETHAMIVAN	2	1,027
CHEMBL200102	PU-H71	2	221
CHEMBL252164	LUMINESPIB	2	1,800
CHEMBL278315	GELDANAMYCIN	2	30,673
CHEMBL383824	ALVESPIMYCIN	2	752
CHEMBL450613	ZERANOL	2	2,088
CHEMBL467399	BIIB021	2	1,606
CHEMBL1232461	MOLIBRESIB	2	1,538
CHEMBL3661115	TAS-116	2	398
CHEMBL2419346	CUDC-305	1

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

3 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs3734704	Toxicity	3	bevacizumab	Hypertension
rs6929249	Toxicity	3	bevacizumab	Hypertension
rs834576	Toxicity	3	bevacizumab	Hypertension

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — Heat shock proteins

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
luminespib	Inhibition	8.7	pIC50
geldanamycin	Inhibition	6.55	pIC50

Binding affinities (BindingDB)

409 measured of 558 human assays (566 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
hsp90_44	IC50	5.22 nM
hsp90_45	IC50	8.4 nM
6-chloro-9-[(4-iodo-3,5-dimethylpyridin-2-yl)methyl]-9H-purin-2-amine	EC50	9 nM
hsp90_129	IC50	10 nM
hsp90_130	IC50	10 nM
hsp90_131	IC50	10 nM
hsp90_161	IC50	10 nM
hsp90_42	IC50	10.8 nM
hsp90_46	IC50	11.5 nM
hsp90_32	IC50	12.1 nM
hsp90_174	IC50	13.7 nM
N-ethyl-5-(5-ethyl-2-hydroxy-4-methoxyphenyl)-4-[4-(morpholin-4-ylmethyl)phenyl]-1,2-oxazole-3-carboxamide	IC50	15 nM
hsp90_128	IC50	15.3 nM
2-amino-6-halopurine analogue, 20	IC50	15.6 nM
5-[2,4-dihydroxy-5-(propan-2-yl)phenyl]-N-ethyl-4-[4-(morpholin-4-ylmethyl)phenyl]-1,2-oxazole-3-carboxamide	EC50	16 nM
2-amino-6-halopurine analogue, 29	IC50	18.3 nM
hsp90_43	IC50	19 nM
hsp90_157	IC50	19.3 nM
6-chloro-9-[(5-methoxy-4,6-dimethylpyridin-3-yl)methyl]-9H-purin-2-amine	EC50	20 nM
N-ethyl-5-{5-[2-(4-fluorophenyl)ethyl]-2,4-dihydroxyphenyl}-4-[4-(morpholin-4-ylmethyl)phenyl]-1,2-oxazole-3-carboxamide	IC50	20 nM
hsp90_26	IC50	20.5 nM
hsp90_87	IC50	22.1 nM
hsp90_85	IC50	23.4 nM
hsp90_36	IC50	23.6 nM
hsp90_40	IC50	24.8 nM
N-Ethyl-3-(5-Chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-1H-pyrazole-5-carboxamide	IC50	25 nM
N-ethyl-5-{5-[2-(4-fluorophenyl)ethyl]-2,4-dihydroxyphenyl}-4-[4-(piperidin-1-ylmethyl)phenyl]-1,2-oxazole-3-carboxamide	IC50	26 nM
N-ethyl-5-{5-[2-(3-fluorophenyl)ethyl]-2,4-dihydroxyphenyl}-4-[4-(morpholin-4-ylmethyl)phenyl]-1,2-oxazole-3-carboxamide	IC50	26 nM
hsp90_37	IC50	26.9 nM
US8835464, 13b	IC50	27 nM	US-9206162: Triazole compounds that modulate Hsp90 activity
6-chloro-9-{[3,5-dimethyl-4-(methylsulfanyl)pyridin-2-yl]methyl}-9H-purin-2-amine	EC50	27 nM
3-(5-chloro-2,4-dihydroxyphenyl)-4-{4-[(1,1-dioxo-1,4-thiomorpholin-4-yl)methyl]phenyl}-N-ethyl-1H-pyrazole-5-carboxamide	IC50	27 nM
hsp90_104	IC50	27.2 nM
hsp90_41	IC50	27.4 nM
diethyl {2-[6-amino-8-({7-bromopyrido[3,4-d][1,3]thiazol-2-yl}sulfanyl)-9H-purin-9-yl]ethyl}phosphonate	EC50	28 nM
5-(5-chloro-2,4-dihydroxyphenyl)-N-ethyl-4-(4-methoxyphenyl)-1,2-oxazole-3-carboxamide	IC50	28 nM
hsp90_25	IC50	28.8 nM
US8835464, 12b	IC50	29 nM	US-9206162: Triazole compounds that modulate Hsp90 activity
5-[2,4-dihydroxy-5-(2-phenylethyl)phenyl]-N-ethyl-4-[4-(morpholin-4-ylmethyl)phenyl]-1,2-oxazole-3-carboxamide	EC50	29 nM
thieno[2,3-d]pyrimidine, 34g	IC50	29 nM
hsp90_12	IC50	29.2 nM
US8835464, 1d	IC50	30 nM	US-9206162: Triazole compounds that modulate Hsp90 activity
diethyl (2-{6-amino-8-[(7-chloro-1,3-benzothiazol-2-yl)sulfanyl]-9H-purin-9-yl}ethyl)phosphonate	EC50	30 nM
diethyl {2-[6-amino-8-({7-chloropyrido[3,4-d][1,3]thiazol-2-yl}sulfanyl)-9H-purin-9-yl]ethyl}phosphonate	EC50	30 nM
hsp90_39	IC50	30.4 nM
hsp90_79	IC50	30.8 nM
8-[(7-chloro-1,3-benzothiazol-2-yl)sulfanyl]-9-{2-[(2,2-dimethylpropyl)amino]ethyl}-9H-purin-6-amine	EC50	35 nM
3-(5-chloro-2,4-dihydroxyphenyl)-N-ethyl-4-(4-{[(2-methanesulfonylethyl)amino]methyl}phenyl)-1H-pyrazole-5-carboxamide	IC50	35 nM
N-ethyl-5-[5-(4-fluorophenyl)-2,4-dihydroxyphenyl]-4-[4-(piperidin-1-ylmethyl)phenyl]-1,2-oxazole-3-carboxamide	EC50	35 nM
5-[2,4-dihydroxy-5-(2-methylpropyl)phenyl]-N-ethyl-4-[4-(morpholin-4-ylmethyl)phenyl]-1,2-oxazole-3-carboxamide	IC50	35 nM

ChEMBL bioactivities

2025 potent at pChembl≥5 of 2395 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.24	Kd	0.057	nM	CHEMBL2443026
10.19	Ki	0.064	nM	LUMINESPIB
10.16	Ki	0.069	nM	LUMINESPIB
9.92	Kd	0.12	nM	CHEMBL2443138
9.89	IC50	0.13	nM	CHEMBL6168361
9.89	IC50	0.13	nM	ONALESPIB
9.80	IC50	0.16	nM	CHEMBL6165710
9.66	Kd	0.22	nM	CHEMBL2443139
9.52	IC50	0.3	nM	CHEMBL6172500
9.51	IC50	0.31	nM	CHEMBL6176585
9.49	IC50	0.32	nM	CHEMBL6167852
9.49	IC50	0.32	nM	CHEMBL6175808
9.46	Kd	0.346	nM	CHEMBL2443044
9.46	Kd	0.35	nM	CHEMBL1917878
9.35	IC50	0.45	nM	CHEMBL6164902
9.34	IC50	0.46	nM	CHEMBL6167303
9.34	IC50	0.46	nM	CHEMBL6175551
9.30	IC50	0.5	nM	CHEMBL6170870
9.28	IC50	0.53	nM	CHEMBL6170534
9.28	IC50	0.53	nM	CHEMBL6170473
9.28	IC50	0.53	nM	CHEMBL6177673
9.27	Kd	0.54	nM	CHEMBL1215539
9.27	Kd	0.54	nM	CHEMBL1215467
9.26	Kd	0.546	nM	CHEMBL3752910
9.26	ED50	0.546	nM	CHEMBL3752910
9.20	IC50	0.63	nM	CHEMBL6174734
9.19	IC50	0.64	nM	CHEMBL6176915
9.19	IC50	0.64	nM	CHEMBL6171794
9.15	Kd	0.71	nM	CHEMBL5174695
9.14	Kd	0.726	nM	SNX-2112
9.14	IC50	0.73	nM	CHEMBL6172357
9.12	IC50	0.76	nM	CHEMBL6165577
9.08	IC50	0.83	nM	CHEMBL6176454
9.06	IC50	0.88	nM	CHEMBL6176570
9.06	IC50	0.88	nM	CHEMBL6174723
9.06	IC50	0.88	nM	CHEMBL6174270
9.06	IC50	0.88	nM	CHEMBL6175381
9.05	IC50	0.9	nM	CHEMBL6170555
9.03	IC50	0.94	nM	CHEMBL6177298
9.03	IC50	0.93	nM	CHEMBL6173322
9.03	IC50	0.94	nM	CHEMBL6165984
9.03	IC50	0.93	nM	CHEMBL6176755
9.00	Ki	1	nM	CHEMBL3309997
9.00	IC50	1	nM	CHEMBL3360305
9.00	IC50	1	nM	SNX-2112
9.00	IC50	1.01	nM	CHEMBL6171889
8.99	IC50	1.03	nM	CHEMBL6177341
8.96	Ki	1.1	nM	SNX-2112
8.95	IC50	1.13	nM	CHEMBL6172681
8.95	IC50	1.13	nM	CHEMBL6169338

PubChem BioAssay actives

1916 with measured affinity, of 5373 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
1,3-dihydroisoindol-2-yl-(2,4-dihydroxy-5-propan-2-ylphenyl)methanone	1324615: Inhibition of HSP90 (unknown origin)	kd	<0.0001	uM
5-(2,4-dihydroxy-5-propan-2-ylphenyl)-N-ethyl-4-[4-(morpholin-4-ylmethyl)phenyl]-1,2-oxazole-3-carboxamide	465289: Binding affinity to HSP90 under reducing conditions in presence of TECP	ki	0.0001	uM
5-[2-[4-(dimethylamino)phenoxy]-4,6-dihydroxyphenyl]-N-(1-methylpiperidin-4-yl)-1,2-oxazole-3-carboxamide	780857: Displacement of FITC-Geldanamycin from Hsp90 (unknown origin) after 18 hrs by fluorescence polarization assay	kd	0.0001	uM
5-[2-[4-(dimethylamino)phenoxy]-4,6-dihydroxyphenyl]-N-[1-(1,4-dioxaspiro[4.5]decan-8-yl)piperidin-4-yl]-1,2-oxazole-3-carboxamide	780857: Displacement of FITC-Geldanamycin from Hsp90 (unknown origin) after 18 hrs by fluorescence polarization assay	kd	0.0001	uM
5-[2,4-dihydroxy-6-[4-(propan-2-ylamino)phenoxy]phenyl]-N-(1-methylpiperidin-4-yl)-1,2-oxazole-3-carboxamide	780857: Displacement of FITC-Geldanamycin from Hsp90 (unknown origin) after 18 hrs by fluorescence polarization assay	kd	0.0002	uM
5-[2,4-dihydroxy-6-(4-nitrophenoxy)phenyl]-N-(1-methylpiperidin-4-yl)-1,2-oxazole-3-carboxamide	780857: Displacement of FITC-Geldanamycin from Hsp90 (unknown origin) after 18 hrs by fluorescence polarization assay	kd	0.0003	uM
N-[(9R)-4-(3H-imidazo[4,5-c]pyridin-2-yl)-9H-fluoren-9-yl]-1H-pyrrolo[2,3-b]pyridine-4-carboxamide	629756: Binding affinity to human Hsp90beta after overnight incubation by fluorescence polarization assay	kd	0.0003	uM
1,3-dihydroisoindol-2-yl-(5-ethyl-2,4-dihydroxyphenyl)methanone	1866070: Inhibition of HSP90 (unknown origin)	kd	0.0005	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148547: Binding affinity to human HSP90AB1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0005	uM
(5-ethyl-2,4-dihydroxyphenyl)-[5-[(4-methylpiperazin-1-yl)methyl]-1,3-dihydroisoindol-2-yl]methanone	1866070: Inhibition of HSP90 (unknown origin)	kd	0.0007	uM
4-[6,6-dimethyl-4-oxo-3-(trifluoromethyl)-5,7-dihydroindazol-1-yl]-2-[(4-hydroxycyclohexyl)amino]benzamide	780857: Displacement of FITC-Geldanamycin from Hsp90 (unknown origin) after 18 hrs by fluorescence polarization assay	kd	0.0007	uM
3-[[5-(1,3-benzodioxol-5-yl)-[1,2,4]triazolo[1,5-c]quinazolin-8-yl]amino]propan-1-ol	1181796: Inhibition of Hsp90 (unknown origin) by FP displacement assay	ki	0.0010	uM
4-(2,4-dichloro-5-methoxyphenyl)-2-[2-(diethylamino)ethylsulfanyl]-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile	695341: Inhibition of fluorescently labeled VER51001 binding to full length human HSP90beta after 30 mins by fluorescence polarization assay	ki	0.0010	uM
4-(2-chloro-4-cyano-5-methoxyphenyl)-2-[2-(diethylamino)ethylsulfanyl]-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile	695341: Inhibition of fluorescently labeled VER51001 binding to full length human HSP90beta after 30 mins by fluorescence polarization assay	ki	0.0010	uM
2-[[4-(2-chloro-5-hydroxy-4-methoxyphenyl)-5-cyano-7H-pyrrolo[2,3-d]pyrimidin-2-yl]sulfanyl]-N,N-dimethylacetamide	695341: Inhibition of fluorescently labeled VER51001 binding to full length human HSP90beta after 30 mins by fluorescence polarization assay	ki	0.0010	uM
2-[[4-(2-chloro-4,5-dimethoxyphenyl)-5-cyano-7H-pyrrolo[2,3-d]pyrimidin-2-yl]sulfanyl]-N,N-dimethylacetamide	695341: Inhibition of fluorescently labeled VER51001 binding to full length human HSP90beta after 30 mins by fluorescence polarization assay	ki	0.0010	uM
2-[[4-(2-chloro-4,5-dimethoxyphenyl)-5-cyano-7H-pyrrolo[2,3-d]pyrimidin-2-yl]sulfanyl]-N-cyclopropylacetamide	695341: Inhibition of fluorescently labeled VER51001 binding to full length human HSP90beta after 30 mins by fluorescence polarization assay	ki	0.0010	uM
2-[[4-(2-chloro-5-hydroxy-4-methoxyphenyl)-5-cyano-7H-pyrrolo[2,3-d]pyrimidin-2-yl]sulfanyl]-N-cyclopropylacetamide	695341: Inhibition of fluorescently labeled VER51001 binding to full length human HSP90beta after 30 mins by fluorescence polarization assay	ki	0.0010	uM
2-[[4-(2-chloro-5-ethoxy-4-methoxyphenyl)-5-cyano-7H-pyrrolo[2,3-d]pyrimidin-2-yl]sulfanyl]-N-cyclopropylacetamide	695341: Inhibition of fluorescently labeled VER51001 binding to full length human HSP90beta after 30 mins by fluorescence polarization assay	ki	0.0010	uM
2-[[4-(2-chloro-4,5-dimethoxyphenyl)-5-cyano-7H-pyrrolo[2,3-d]pyrimidin-2-yl]sulfanyl]-N-propan-2-ylacetamide	695341: Inhibition of fluorescently labeled VER51001 binding to full length human HSP90beta after 30 mins by fluorescence polarization assay	ki	0.0010	uM
2-[[4-(2-chloro-5-ethoxy-4-methoxyphenyl)-5-cyano-7H-pyrrolo[2,3-d]pyrimidin-2-yl]sulfanyl]-N-propan-2-ylacetamide	695341: Inhibition of fluorescently labeled VER51001 binding to full length human HSP90beta after 30 mins by fluorescence polarization assay	ki	0.0010	uM
2-[[4-(2-chloro-5-ethoxy-4-methoxyphenyl)-5-cyano-7H-pyrrolo[2,3-d]pyrimidin-2-yl]sulfanyl]-N-ethylacetamide	695341: Inhibition of fluorescently labeled VER51001 binding to full length human HSP90beta after 30 mins by fluorescence polarization assay	ki	0.0010	uM
N-tert-butyl-2-[[4-(2-chloro-5-hydroxy-4-methoxyphenyl)-5-cyano-7H-pyrrolo[2,3-d]pyrimidin-2-yl]sulfanyl]acetamide	695341: Inhibition of fluorescently labeled VER51001 binding to full length human HSP90beta after 30 mins by fluorescence polarization assay	ki	0.0010	uM
N-tert-butyl-2-[[4-(2-chloro-4,5-dimethoxyphenyl)-5-cyano-7H-pyrrolo[2,3-d]pyrimidin-2-yl]sulfanyl]acetamide	695341: Inhibition of fluorescently labeled VER51001 binding to full length human HSP90beta after 30 mins by fluorescence polarization assay	ki	0.0010	uM
2-[[4-(2-chloro-4,5-dimethoxyphenyl)-5-cyano-7H-pyrrolo[2,3-d]pyrimidin-2-yl]sulfanyl]-N-(2,2,2-trifluoroethyl)acetamide	695341: Inhibition of fluorescently labeled VER51001 binding to full length human HSP90beta after 30 mins by fluorescence polarization assay	ki	0.0010	uM
(7R)-2-amino-7-[4-fluoro-2-(6-methoxy-2-pyridinyl)phenyl]-4-methyl-7,8-dihydro-6H-pyrido[4,3-d]pyrimidin-5-one	1170429: Inhibition of full-length HSP90 (unknown origin)	ic50	0.0010	uM
2-[2-(azetidin-1-yl)-2-oxoethyl]sulfanyl-4-(2-chloro-5-hydroxy-4-methoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile	695341: Inhibition of fluorescently labeled VER51001 binding to full length human HSP90beta after 30 mins by fluorescence polarization assay	ki	0.0010	uM
2-[2-(azetidin-1-yl)-2-oxoethyl]sulfanyl-4-(2-chloro-4,5-dimethoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile	695341: Inhibition of fluorescently labeled VER51001 binding to full length human HSP90beta after 30 mins by fluorescence polarization assay	ki	0.0010	uM
2-[[4-(2-chloro-4,5-dimethoxyphenyl)-5-cyano-7H-pyrrolo[2,3-d]pyrimidin-2-yl]sulfanyl]-N-methylacetamide	695341: Inhibition of fluorescently labeled VER51001 binding to full length human HSP90beta after 30 mins by fluorescence polarization assay	ki	0.0010	uM
5-[3-[6-amino-8-[(6-iodo-1,3-benzodioxol-5-yl)sulfanyl]purin-9-yl]propylcarbamothioylamino]-2-(3-hydroxy-6-oxoxanthen-9-yl)benzoic acid	767757: Binding affinity to recombinant HSP90beta (unknown origin) by fluorescence polarization assay	kd	0.0016	uM
2-amino-4-[2,4-dichloro-6-[2-(4-fluoropyrazol-1-yl)ethoxy]phenyl]-N-(4,4-difluoro-2-methylpentan-2-yl)-5,7-dihydropyrrolo[3,4-d]pyrimidine-6-carboxamide	1232323: Inhibition of human recombinant HSP90 by scintillation proximity competition binding assay	ki	0.0017	uM
6-chloro-9-[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]purin-2-amine	1662428: Inhibition of recombinant His-tagged full length human HSP90 (9 to 236 residues) expressed in Escherichia coli BL21(DE3) cells after 18 hrs by fluorescence polarization displacement assay	ki	0.0017	uM
9-[(4-bromo-3,5-dimethyl-2-pyridinyl)methyl]-6-chloropurin-2-amine	288528: Binding affinity to human recombinant HSP90 in MCF7 cell lysates assessed as inhibition of biotinylated-geldanamycin binding	ic50	0.0020	uM
4-[5-(4-methoxyphenyl)thiadiazol-4-yl]-6-propan-2-ylbenzene-1,3-diol	2108969: Binding affinity to human N-terminal his tagged Hsp90beta (1 to 239 residues) expressed in Escherichia coli (DE3) strain assessed as dissociation constant by Fluorescent thermal shift assay	kd	0.0020	uM
4-[2,4-dichloro-5-[2-(diethylamino)ethoxy]phenyl]-2-methylsulfanyl-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile	695341: Inhibition of fluorescently labeled VER51001 binding to full length human HSP90beta after 30 mins by fluorescence polarization assay	ki	0.0020	uM
2-[[4-(2-chloro-4,5-dimethoxyphenyl)-5-cyano-7H-pyrrolo[2,3-d]pyrimidin-2-yl]sulfanyl]-N-ethylacetamide	695341: Inhibition of fluorescently labeled VER51001 binding to full length human HSP90beta after 30 mins by fluorescence polarization assay	ki	0.0020	uM
2-[[4-(2-chloro-5-hydroxy-4-methoxyphenyl)-5-cyano-7H-pyrrolo[2,3-d]pyrimidin-2-yl]sulfanyl]-N-(2-fluoroethyl)acetamide	695341: Inhibition of fluorescently labeled VER51001 binding to full length human HSP90beta after 30 mins by fluorescence polarization assay	ki	0.0020	uM
[(4E,6Z,8R,9S,10E,12S,13R,14S,16R)-19-[2-(dimethylamino)ethylamino]-13-hydroxy-8,14-dimethoxy-4,10,12,16-tetramethyl-3,20,22-trioxo-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18-pentaen-9-yl] carbamate	1063124: Binding affinity to human N-terminal polyHis-tagged HSP90beta (D9 to E236) expressed in insect sf9 cells after 3 hrs by fluorescence polarization assay	ki	0.0020	uM
2-amino-4-[2,4-dichloro-6-[2-(4-fluoropyrazol-1-yl)ethoxy]phenyl]-N-(4,4,4-trifluoro-2-methylbutan-2-yl)-5,7-dihydropyrrolo[3,4-d]pyrimidine-6-carboxamide	1232323: Inhibition of human recombinant HSP90 by scintillation proximity competition binding assay	ki	0.0021	uM
(4R,6R,8R,9Z,11E)-16-chloro-17,19-dihydroxy-4-methyl-3,7-dioxatricyclo[13.4.0.06,8]nonadeca-1(15),9,11,16,18-pentaene-2,13-dione	763529: Binding affinity to human Hsp90 by surface plasmon resonance analysis	kd	0.0022	uM
24-[2-[4-[[(4E,6Z,8S,9S,10E,12S,13R,14S,16R)-9-carbamoyloxy-13-hydroxy-8,14-dimethoxy-4,10,12,16-tetramethyl-3,20,22-trioxo-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18-pentaen-19-yl]amino]butylamino]-2-oxoethyl]-5,5,27,27-tetramethyl-16-oxa-20-aza-12-azoniaheptacyclo[15.11.0.03,15.04,12.06,11.020,28.021,26]octacosa-1(28),2,4(12),6(11),7,9,21(26),22,24-nonaene-8-sulfonate	767757: Binding affinity to recombinant HSP90beta (unknown origin) by fluorescence polarization assay	kd	0.0022	uM
5-[[3-[6-amino-8-[(6-iodo-1,3-benzodioxol-5-yl)sulfanyl]purin-9-yl]propyl-propan-2-ylcarbamothioyl]amino]-2-(3-hydroxy-6-oxoxanthen-9-yl)benzoic acid	767757: Binding affinity to recombinant HSP90beta (unknown origin) by fluorescence polarization assay	kd	0.0028	uM
2-[[4-[[1-[(9,10-dioxoanthracen-2-yl)methyl]triazol-4-yl]methoxymethyl]triazol-1-yl]methyl]anthracene-9,10-dione	763529: Binding affinity to human Hsp90 by surface plasmon resonance analysis	kd	0.0028	uM
2-methylpropyl N-[(4E,6Z,8S,9S,10E,12S,13R,14S,16R)-9-carbamoyloxy-13-hydroxy-8,14-dimethoxy-4,10,12,16-tetramethyl-3,20,22-trioxo-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18-pentaen-19-yl]carbamate	87626: Concentration of test compound required for inhibition of binding of rHsp90 in MCF-7 cell lysate	ic50	0.0030	uM
6-chloro-9-[(4-iodo-3,5-dimethyl-2-pyridinyl)methyl]purin-2-amine	288528: Binding affinity to human recombinant HSP90 in MCF7 cell lysates assessed as inhibition of biotinylated-geldanamycin binding	ic50	0.0030	uM
2,4-dihydroxy-N-methyl-N-[(2-methylphenyl)methyl]-5-[4-(2-methylphenyl)-5-oxo-1H-1,2,4-triazol-3-yl]benzamide	1375477: Binding affinity to recombinant N-terminal Hsp90 (unknown origin) by SPR method	kd	0.0030	uM
4-[5-(4-methylphenyl)thiadiazol-4-yl]-6-propan-2-ylbenzene-1,3-diol	2108974: Binding affinity to human N-terminal his tagged Hsp90beta (1 to 239 residues) expressed in Escherichia coli (DE3) strain assessed as dissociation constant by ITC method	kd	0.0030	uM
4-[2-chloro-5-[2-[(3S)-3-fluoropyrrolidin-1-yl]ethoxy]-4-methoxyphenyl]-2-methylsulfanyl-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile	695341: Inhibition of fluorescently labeled VER51001 binding to full length human HSP90beta after 30 mins by fluorescence polarization assay	ki	0.0030	uM
2-[[4-(2-chloro-5-hydroxy-4-methoxyphenyl)-5-cyano-7H-pyrrolo[2,3-d]pyrimidin-2-yl]sulfanyl]-N-propan-2-ylacetamide	695341: Inhibition of fluorescently labeled VER51001 binding to full length human HSP90beta after 30 mins by fluorescence polarization assay	ki	0.0030	uM
[(4E,6Z,8S,9S,10E,12S,13R,14S,16R)-13-hydroxy-8,14-dimethoxy-4,10,12,16-tetramethyl-3,20,22-trioxo-19-(prop-2-enylamino)-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18-pentaen-9-yl] carbamate	421300: Inhibition of Hsp90 in human AU565 cells assessed as Her2 degradation after 24 hrs by high content screening	ic50	0.0030	uM

CTD chemical–gene interactions

118 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Arsenic Trioxide	increases expression, affects response to substance, decreases expression	5
Tobacco Smoke Pollution	affects expression, increases expression	4
bisphenol A	increases expression, affects reaction, affects cotreatment, decreases expression	3
sodium arsenite	decreases expression, increases expression	3
Estradiol	affects reaction, increases expression, affects expression	3
Tretinoin	decreases expression, increases acetylation	3
bisphenol F	increases expression, affects cotreatment, decreases expression	2
cobaltous chloride	affects binding, increases reaction, increases expression	2
cadmium sulfate	increases expression	2
nickel acetate	decreases reaction, increases expression, affects expression, decreases expression	2
bisphenol S	increases expression, affects cotreatment, decreases expression	2
Vorinostat	decreases expression	2
Benzo(a)pyrene	increases methylation, increases mutagenesis	2
Cadmium	increases expression	2
Copper	affects binding, decreases expression	2
Ivermectin	increases expression, decreases expression, affects cotreatment	2
Lipopolysaccharides	affects expression, affects response to substance, affects cotreatment, decreases expression	2
Cyclosporine	decreases methylation, increases expression	2
Cadmium Chloride	affects expression, decreases expression	2
beta-Naphthoflavone	increases expression	2
Copper Sulfate	decreases expression, increases expression	2
FR900359	affects phosphorylation	1
9-hydroxyoctadecadienoic acid	decreases expression	1
PF-06840003	decreases reaction, decreases expression	1
geldanamycin	increases expression	1
cinobufagin	decreases expression	1
uranyl acetate	affects expression	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
pyrithione zinc	increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1

ChEMBL screening assays

1430 unique, capped per target: 1372 binding, 40 admet, 16 functional, 2 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1004497	Binding	Binding affinity to human recombinant Hsp90 expressed in Escherichia coli assessed as thermal shift by differential scanning fluorimetry	Discovery of a potent and selective inhibitor for human carbonyl reductase 1 from propionate scanning applied to the macrolide zearalenone. — Bioorg Med Chem
CHEMBL1613874	Functional	PUBCHEM_BIOASSAY: Tumor Hsp90 Inhibitors Dose Response Confirmation. (Class of assay: confirmatory) [Related pubchem assays: 429 (Primary screen preceding this dose response confirmation assay.)]	PubChem BioAssay data set
CHEMBL4019105	ADMET	Inhibition of HSP90 in human HeLa cells assessed as induction of HSP70 protein expression at 20 uM after 6 hrs by Western blot method	Paralog Specificity Determines Subcellular Distribution, Action Mechanism, and Anticancer Activity of TRAP1 Inhibitors. — J Med Chem

Cellosaurus cell lines

3 cell lines: 2 transformed cell line, 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1C9	Abcam A-431 HSP90AB1 KO	Cancer cell line	Female
CVCL_B2Z6	Abcam HEK293T HSP90AB1 KO	Transformed cell line	Female
CVCL_D9GE	Ubigene HEK293 HSP90AB1 KO	Transformed cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.