Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTR69EG7)

• DOT Name: Heat shock protein HSP 90-beta (HSP90AB1)
• Synonyms: HSP 90; Heat shock 84 kDa; HSP 84; HSP84
• Gene Name: HSP90AB1
• UniProt ID: HS90B_HUMAN
• PDB ID: 1QZ2; 1UYM; 2L6J; 3FWV; 3NMQ; 3PRY; 3UQ3; 5FWK; 5FWL; 5FWM; 5FWP; 5UC4; 5UCH; 5UCI; 5UCJ; 6N8W; 6N8Y; 7ULJ; 7Z37; 7Z38; 7ZR0; 7ZR5; 7ZR6; 7ZUB; 8EOA; 8EOB; 8GAE; 8GFT
• Pfam ID: PF13589 ; PF00183
• Sequence:
  MPEEVHHGEEEVETFAFQAEIAQLMSLIINTFYSNKEIFLRELISNASDALDKIRYESLT
  DPSKLDSGKELKIDIIPNPQERTLTLVDTGIGMTKADLINNLGTIAKSGTKAFMEALQAG
  ADISMIGQFGVGFYSAYLVAEKVVVITKHNDDEQYAWESSAGGSFTVRADHGEPIGRGTK
  VILHLKEDQTEYLEERRVKEVVKKHSQFIGYPITLYLEKEREKEISDDEAEEEKGEKEEE
  DKDDEEKPKIEDVGSDEEDDSGKDKKKKTKKIKEKYIDQEELNKTKPIWTRNPDDITQEE
  YGEFYKSLTNDWEDHLAVKHFSVEGQLEFRALLFIPRRAPFDLFENKKKKNNIKLYVRRV
  FIMDSCDELIPEYLNFIRGVVDSEDLPLNISREMLQQSKILKVIRKNIVKKCLELFSELA
  EDKENYKKFYEAFSKNLKLGIHEDSTNRRRLSELLRYHTSQSGDEMTSLSEYVSRMKETQ
  KSIYYITGESKEQVANSAFVERVRKRGFEVVYMTEPIDEYCVQQLKEFDGKSLVSVTKEG
  LELPEDEEEKKKMEESKAKFENLCKLMKEILDKKVEKVTISNRLVSSPCCIVTSTYGWTA
  NMERIMKAQALRDNSTMGYMMAKKHLEINPDHPIVETLRQKAEADKNDKAVKDLVVLLFE
  TALLSSGFSLEDPQTHSNRIYRMIKLGLGIDEDEVAAEEPNAAVPDEIPPLEGDEDASRM
  EEVD
• 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 (Probable).
• KEGG Pathway:
  Protein processing in endoplasmic reticulum (hsa04141)
  PI3K-Akt sig.ling pathway (hsa04151)
  Necroptosis (hsa04217)
  Antigen processing and presentation (hsa04612)
  NOD-like receptor sig.ling pathway (hsa04621)
  IL-17 sig.ling pathway (hsa04657)
  Th17 cell differentiation (hsa04659)
  Progesterone-mediated oocyte maturation (hsa04914)
  Estrogen sig.ling pathway (hsa04915)
  Salmonella infection (hsa05132)
  Pathways in cancer (hsa05200)
  Chemical carcinogenesis - receptor activation (hsa05207)
  Prostate cancer (hsa05215)
  Lipid and atherosclerosis (hsa05417)
  Fluid shear stress and atherosclerosis (hsa05418)
• Reactome Pathway:
  Regulation of actin dynamics for phagocytic cup formation (R-HSA-2029482)
  HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand (R-HSA-3371497)
  HSF1 activation (R-HSA-3371511)
  Attenuation phase (R-HSA-3371568)
  HSF1-dependent transactivation (R-HSA-3371571)
  Sema3A PAK dependent Axon repulsion (R-HSA-399954)
  Uptake and function of diphtheria toxin (R-HSA-5336415)
  Neutrophil degranulation (R-HSA-6798695)
  The NLRP3 inflammasome (R-HSA-844456)
  The role of GTSE1 in G2/M progression after G2 checkpoint (R-HSA-8852276)
  Aryl hydrocarbon receptor signalling (R-HSA-8937144)
  ESR-mediated signaling (R-HSA-8939211)
  RHOBTB2 GTPase cycle (R-HSA-9013418)
  Estrogen-dependent gene expression (R-HSA-9018519)
  Chaperone Mediated Autophagy (R-HSA-9613829)
  Purinergic signaling in leishmaniasis infection (R-HSA-9660826)
  Potential therapeutics for SARS (R-HSA-9679191)
  SARS-CoV-2 activates/modulates innate and adaptive immune responses (R-HSA-9705671)
  DDX58/IFIH1-mediated induction of interferon-alpha/beta (R-HSA-168928)

Molecular Interaction Atlas (MIA) of This DOT

32 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Heat shock protein HSP 90-beta (HSP90AB1).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Heat shock protein HSP 90-beta (HSP90AB1).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Heat shock protein HSP 90-beta (HSP90AB1).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Heat shock protein HSP 90-beta (HSP90AB1).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Heat shock protein HSP 90-beta (HSP90AB1).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Heat shock protein HSP 90-beta (HSP90AB1).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Heat shock protein HSP 90-beta (HSP90AB1).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Heat shock protein HSP 90-beta (HSP90AB1).	[8]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Heat shock protein HSP 90-beta (HSP90AB1).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Heat shock protein HSP 90-beta (HSP90AB1).	[10]
Selenium	DM25CGV	Approved	Selenium increases the expression of Heat shock protein HSP 90-beta (HSP90AB1).	[11]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Heat shock protein HSP 90-beta (HSP90AB1).	[12]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Heat shock protein HSP 90-beta (HSP90AB1).	[13]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Heat shock protein HSP 90-beta (HSP90AB1).	[14]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Heat shock protein HSP 90-beta (HSP90AB1).	[15]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of Heat shock protein HSP 90-beta (HSP90AB1).	[16]
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial increases the expression of Heat shock protein HSP 90-beta (HSP90AB1).	[17]
Motexafin gadolinium	DMEJKRF	Approved	Motexafin gadolinium increases the expression of Heat shock protein HSP 90-beta (HSP90AB1).	[17]
Dopamine	DMPGUCF	Approved	Dopamine increases the expression of Heat shock protein HSP 90-beta (HSP90AB1).	[18]
Etretinate	DM2CZFA	Approved	Etretinate decreases the expression of Heat shock protein HSP 90-beta (HSP90AB1).	[19]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Heat shock protein HSP 90-beta (HSP90AB1).	[2]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Heat shock protein HSP 90-beta (HSP90AB1).	[11]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene decreases the expression of Heat shock protein HSP 90-beta (HSP90AB1).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Heat shock protein HSP 90-beta (HSP90AB1).	[21]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Heat shock protein HSP 90-beta (HSP90AB1).	[23]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Heat shock protein HSP 90-beta (HSP90AB1).	[6]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of Heat shock protein HSP 90-beta (HSP90AB1).	[24]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Heat shock protein HSP 90-beta (HSP90AB1).	[25]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine increases the expression of Heat shock protein HSP 90-beta (HSP90AB1).	[26]
Paraoxon	DMN4ZKC	Investigative	Paraoxon decreases the expression of Heat shock protein HSP 90-beta (HSP90AB1).	[27]
Choline	DM5D9YK	Investigative	Choline affects the expression of Heat shock protein HSP 90-beta (HSP90AB1).	[28]
9-hydroxyoctadecadienoic acid	DM0FWNJ	Investigative	9-hydroxyoctadecadienoic acid decreases the expression of Heat shock protein HSP 90-beta (HSP90AB1).	[29]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tanespimycin	DMNLQHK	Phase 2	Tanespimycin affects the binding of Heat shock protein HSP 90-beta (HSP90AB1).	[20]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Heat shock protein HSP 90-beta (HSP90AB1).	[22]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Heat shock protein HSP 90-beta (HSP90AB1).	[22]

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