Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYNJ4KP)

• DOT Name: Heat shock factor protein 1 (HSF1)
• Synonyms: HSF 1; Heat shock transcription factor 1; HSTF 1
• Gene Name: HSF1
• UniProt ID: HSF1_HUMAN
• PDB ID: 2LDU; 5D5U; 5D5V; 5HDG; 5HDN; 7DCJ; 7DCS; 7DCT
• Pfam ID: PF00447 ; PF06546
• Sequence:
  MDLPVGPGAAGPSNVPAFLTKLWTLVSDPDTDALICWSPSGNSFHVFDQGQFAKEVLPKY
  FKHNNMASFVRQLNMYGFRKVVHIEQGGLVKPERDDTEFQHPCFLRGQEQLLENIKRKVT
  SVSTLKSEDIKIRQDSVTKLLTDVQLMKGKQECMDSKLLAMKHENEALWREVASLRQKHA
  QQQKVVNKLIQFLISLVQSNRILGVKRKIPLMLNDSGSAHSMPKYSRQFSLEHVHGSGPY
  SAPSPAYSSSSLYAPDAVASSGPIISDITELAPASPMASPGGSIDERPLSSSPLVRVKEE
  PPSPPQSPRVEEASPGRPSSVDTLLSPTALIDSILRESEPAPASVTALTDARGHTDTEGR
  PPSPPPTSTPEKCLSVACLDKNELSDHLDAMDSNLDNLQTMLSSHGFSVDTSALLDLFSP
  SVTVPDMSLPDLDSSLASIQELLSPQEPPRPPEAENSSPDSGKQLVHYTAQPLFLLDPGS
  VDTGSNDLPVLFELGEGSYFSEGDGFAEDPTISLLTGSEPPKAKDPTVS
• Function: Functions as a stress-inducible and DNA-binding transcription factor that plays a central role in the transcriptional activation of the heat shock response (HSR), leading to the expression of a large class of molecular chaperones, heat shock proteins (HSPs), that protect cells from cellular insult damage. In unstressed cells, is present in a HSP90-containing multichaperone complex that maintains it in a non-DNA-binding inactivated monomeric form. Upon exposure to heat and other stress stimuli, undergoes homotrimerization and activates HSP gene transcription through binding to site-specific heat shock elements (HSEs) present in the promoter regions of HSP genes. Upon heat shock stress, forms a chromatin-associated complex with TTC5/STRAP and p300/EP300 to stimulate HSR transcription, therefore increasing cell survival. Activation is reversible, and during the attenuation and recovery phase period of the HSR, returns to its unactivated form. Binds to inverted 5'-NGAAN-3' pentamer DNA sequences. Binds to chromatin at heat shock gene promoters. Activates transcription of transcription factor FOXR1 which in turn activates transcription of the heat shock chaperones HSPA1A and HSPA6 and the antioxidant NADPH-dependent reductase DHRS2. Also serves several other functions independently of its transcriptional activity. Involved in the repression of Ras-induced transcriptional activation of the c-fos gene in heat-stressed cells. Positively regulates pre-mRNA 3'-end processing and polyadenylation of HSP70 mRNA upon heat-stressed cells in a symplekin (SYMPK)-dependent manner. Plays a role in nuclear export of stress-induced HSP70 mRNA. Plays a role in the regulation of mitotic progression. Also plays a role as a negative regulator of non-homologous end joining (NHEJ) repair activity in a DNA damage-dependent manner. Involved in stress-induced cancer cell proliferation in a IER5-dependent manner ; (Microbial infection) Plays a role in latent human immunodeficiency virus (HIV-1) transcriptional reactivation. Binds to the HIV-1 long terminal repeat promoter (LTR) to reactivate viral transcription by recruiting cellular transcriptional elongation factors, such as CDK9, CCNT1 and EP300.
• KEGG Pathway: Legionellosis (hsa05134)
• Reactome Pathway:
  HSF1 activation (R-HSA-3371511)
  Attenuation phase (R-HSA-3371568)
  HSF1-dependent transactivation (R-HSA-3371571)
  Aggrephagy (R-HSA-9646399)
  Regulation of HSF1-mediated heat shock response (R-HSA-3371453)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Quercetin	DM3NC4M	Approved	Heat shock factor protein 1 (HSF1) increases the response to substance of Quercetin.	[25]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Heat shock factor protein 1 (HSF1).	[1]
Estradiol	DMUNTE3	Approved	Estradiol increases the phosphorylation of Heat shock factor protein 1 (HSF1).	[7]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Heat shock factor protein 1 (HSF1).	[17]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Heat shock factor protein 1 (HSF1).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the phosphorylation of Heat shock factor protein 1 (HSF1).	[7]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Heat shock factor protein 1 (HSF1).	[19]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the phosphorylation of Heat shock factor protein 1 (HSF1).	[22]
propylpyrazoletriol	DMTCP8K	Investigative	propylpyrazoletriol increases the phosphorylation of Heat shock factor protein 1 (HSF1).	[7]

88 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 factor protein 1 (HSF1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Heat shock factor protein 1 (HSF1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Heat shock factor protein 1 (HSF1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Heat shock factor protein 1 (HSF1).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the activity of Heat shock factor protein 1 (HSF1).	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the activity of Heat shock factor protein 1 (HSF1).	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Heat shock factor protein 1 (HSF1).	[8]
Carbamazepine	DMZOLBI	Approved	Carbamazepine increases the activity of Heat shock factor protein 1 (HSF1).	[6]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Heat shock factor protein 1 (HSF1).	[9]
Menadione	DMSJDTY	Approved	Menadione increases the activity of Heat shock factor protein 1 (HSF1).	[6]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the activity of Heat shock factor protein 1 (HSF1).	[6]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Heat shock factor protein 1 (HSF1).	[10]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the activity of Heat shock factor protein 1 (HSF1).	[6]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the activity of Heat shock factor protein 1 (HSF1).	[6]
Aspirin	DM672AH	Approved	Aspirin increases the activity of Heat shock factor protein 1 (HSF1).	[11]
Diclofenac	DMPIHLS	Approved	Diclofenac increases the activity of Heat shock factor protein 1 (HSF1).	[6]
Indomethacin	DMSC4A7	Approved	Indomethacin increases the activity of Heat shock factor protein 1 (HSF1).	[12]
Azacitidine	DMTA5OE	Approved	Azacitidine decreases the activity of Heat shock factor protein 1 (HSF1).	[6]
Sulindac	DM2QHZU	Approved	Sulindac increases the activity of Heat shock factor protein 1 (HSF1).	[11]
Ibuprofen	DM8VCBE	Approved	Ibuprofen increases the activity of Heat shock factor protein 1 (HSF1).	[11]
Imatinib	DM7RJXL	Approved	Imatinib increases the expression of Heat shock factor protein 1 (HSF1).	[14]
Clotrimazole	DMMFCIH	Approved	Clotrimazole increases the activity of Heat shock factor protein 1 (HSF1).	[6]
Nifedipine	DMSVOZT	Approved	Nifedipine increases the activity of Heat shock factor protein 1 (HSF1).	[6]
Imipramine	DM2NUH3	Approved	Imipramine decreases the activity of Heat shock factor protein 1 (HSF1).	[6]
Teriflunomide	DMQ2FKJ	Approved	Teriflunomide increases the activity of Heat shock factor protein 1 (HSF1).	[6]
Ethacrynic acid	DM60QMR	Approved	Ethacrynic acid increases the activity of Heat shock factor protein 1 (HSF1).	[6]
Promegestone	DMK4S8I	Approved	Promegestone increases the activity of Heat shock factor protein 1 (HSF1).	[6]
Furosemide	DMMQ8ZG	Approved	Furosemide increases the activity of Heat shock factor protein 1 (HSF1).	[6]
Propylthiouracil	DM6D7N8	Approved	Propylthiouracil increases the activity of Heat shock factor protein 1 (HSF1).	[6]
Promethazine	DM6I5GR	Approved	Promethazine decreases the activity of Heat shock factor protein 1 (HSF1).	[6]
Albendazole	DMYZ57N	Approved	Albendazole increases the activity of Heat shock factor protein 1 (HSF1).	[6]
Phenoxybenzamine	DM8KSQH	Approved	Phenoxybenzamine increases the activity of Heat shock factor protein 1 (HSF1).	[6]
Fotemustine	DMV62ED	Approved	Fotemustine increases the activity of Heat shock factor protein 1 (HSF1).	[6]
Rivastigmine	DMG629M	Approved	Rivastigmine increases the activity of Heat shock factor protein 1 (HSF1).	[15]
Chlorpheniramine	DM5URA2	Approved	Chlorpheniramine decreases the activity of Heat shock factor protein 1 (HSF1).	[6]
Nitrofurantoin	DM7PQIK	Approved	Nitrofurantoin increases the activity of Heat shock factor protein 1 (HSF1).	[6]
Thiopental	DMGP8AX	Approved	Thiopental increases the activity of Heat shock factor protein 1 (HSF1).	[16]
Cyproheptadine	DM92AH3	Approved	Cyproheptadine increases the activity of Heat shock factor protein 1 (HSF1).	[6]
Papaverine	DMCA9QP	Approved	Papaverine increases the activity of Heat shock factor protein 1 (HSF1).	[6]
Oxaprozin	DM9UB0P	Approved	Oxaprozin increases the activity of Heat shock factor protein 1 (HSF1).	[6]
Ceftazidime	DM41GRA	Approved	Ceftazidime decreases the activity of Heat shock factor protein 1 (HSF1).	[6]
Phenprocoumon	DMDO279	Approved	Phenprocoumon decreases the activity of Heat shock factor protein 1 (HSF1).	[6]
Oxyphenbutazone	DMPZS7U	Approved	Oxyphenbutazone increases the activity of Heat shock factor protein 1 (HSF1).	[6]
Pyridine	DMF8CJ9	Phase 4	Pyridine increases the activity of Heat shock factor protein 1 (HSF1).	[6]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the activity of Heat shock factor protein 1 (HSF1).	[6]
Fenretinide	DMRD5SP	Phase 3	Fenretinide increases the activity of Heat shock factor protein 1 (HSF1).	[6]
Bardoxolone methyl	DMODA2X	Phase 3	Bardoxolone methyl increases the activity of Heat shock factor protein 1 (HSF1).	[6]
I3C	DMIGFOR	Phase 3	I3C increases the activity of Heat shock factor protein 1 (HSF1).	[6]
MLN4924	DMP36KD	Phase 3	MLN4924 increases the activity of Heat shock factor protein 1 (HSF1).	[6]
APR-246	DMNFADH	Phase 2	APR-246 increases the activity of Heat shock factor protein 1 (HSF1).	[6]
Tanespimycin	DMNLQHK	Phase 2	Tanespimycin increases the activity of Heat shock factor protein 1 (HSF1).	[6]
PD-0325901	DM27D4J	Phase 2	PD-0325901 decreases the activity of Heat shock factor protein 1 (HSF1).	[6]
CERC-801	DM3SZ7P	Phase 2	CERC-801 increases the activity of Heat shock factor protein 1 (HSF1).	[6]
BEZ235	DMKBRDL	Phase 2	BEZ235 decreases the activity of Heat shock factor protein 1 (HSF1).	[6]
SPI-1005	DM6XFHS	Phase 2 Trial	SPI-1005 increases the activity of Heat shock factor protein 1 (HSF1).	[6]
H-1152	DM8XH3S	Phase 2	H-1152 decreases the activity of Heat shock factor protein 1 (HSF1).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the activity of Heat shock factor protein 1 (HSF1).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the activity of Heat shock factor protein 1 (HSF1).	[6]
Sphingosine-1-Phosphate	DMJCQKA	Phase 1	Sphingosine-1-Phosphate increases the activity of Heat shock factor protein 1 (HSF1).	[6]
PLX-4720	DMBK9AM	Phase 1	PLX-4720 decreases the activity of Heat shock factor protein 1 (HSF1).	[6]
HSP-990	DML6HP3	Phase 1	HSP-990 increases the activity of Heat shock factor protein 1 (HSF1).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Heat shock factor protein 1 (HSF1).	[18]
PMID26882240-Compound-32	DMJS4RP	Patented	PMID26882240-Compound-32 increases the activity of Heat shock factor protein 1 (HSF1).	[6]
MG-132	DMKA2YS	Preclinical	MG-132 increases the activity of Heat shock factor protein 1 (HSF1).	[20]
Celastrol	DMWQIJX	Preclinical	Celastrol increases the activity of Heat shock factor protein 1 (HSF1).	[6]
Piperlongumine	DMIZCOE	Preclinical	Piperlongumine increases the activity of Heat shock factor protein 1 (HSF1).	[6]
Nimesulide	DMR1NMD	Terminated	Nimesulide increases the activity of Heat shock factor protein 1 (HSF1).	[6]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the activity of Heat shock factor protein 1 (HSF1).	[6]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the activity of Heat shock factor protein 1 (HSF1).	[6]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the activity of Heat shock factor protein 1 (HSF1).	[6]
D-glucose	DMMG2TO	Investigative	D-glucose decreases the activity of Heat shock factor protein 1 (HSF1).	[6]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone decreases the activity of Heat shock factor protein 1 (HSF1).	[6]
Rapamycin Immunosuppressant Drug	DM678IB	Investigative	Rapamycin Immunosuppressant Drug increases the activity of Heat shock factor protein 1 (HSF1).	[6]
acrolein	DMAMCSR	Investigative	acrolein increases the activity of Heat shock factor protein 1 (HSF1).	[6]
Cycloheximide	DMGDA3C	Investigative	Cycloheximide decreases the activity of Heat shock factor protein 1 (HSF1).	[6]
Linalool	DMGZQ5P	Investigative	Linalool increases the expression of Heat shock factor protein 1 (HSF1).	[23]
2-tert-butylbenzene-1,4-diol	DMNXI1E	Investigative	2-tert-butylbenzene-1,4-diol increases the expression of Heat shock factor protein 1 (HSF1).	[8]
15-deoxy-Delta(12, 14)-prostaglandin J(2)	DM8VUX3	Investigative	15-deoxy-Delta(12, 14)-prostaglandin J(2) increases the activity of Heat shock factor protein 1 (HSF1).	[6]
Protoporphyrin IX	DMWYE7A	Investigative	Protoporphyrin IX increases the activity of Heat shock factor protein 1 (HSF1).	[6]
Isoarnebin 4	DM0B7NO	Investigative	Isoarnebin 4 increases the activity of Heat shock factor protein 1 (HSF1).	[6]
L-Serine	DM6WPIS	Investigative	L-Serine increases the activity of Heat shock factor protein 1 (HSF1).	[6]
Ginsenoside RG3	DMFN58T	Investigative	Ginsenoside RG3 decreases the expression of Heat shock factor protein 1 (HSF1).	[24]
G418	DMKTJBU	Investigative	G418 increases the activity of Heat shock factor protein 1 (HSF1).	[6]
Asacolitin	DM3WVPJ	Investigative	Asacolitin decreases the activity of Heat shock factor protein 1 (HSF1).	[6]
CPI-203	DMXSYTA	Investigative	CPI-203 increases the activity of Heat shock factor protein 1 (HSF1).	[6]
AR-00341677	DMK2XB7	Investigative	AR-00341677 increases the activity of Heat shock factor protein 1 (HSF1).	[6]
NC1153	DM6XGFE	Investigative	NC1153 increases the activity of Heat shock factor protein 1 (HSF1).	[6]
Acetate Ion	DMD08RH	Investigative	Acetate Ion decreases the activity of Heat shock factor protein 1 (HSF1).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Simvastatin	DM30SGU	Approved	Simvastatin affects the localization of Heat shock factor protein 1 (HSF1).	[13]
Wortmannin	DM8EVK5	Terminated	Wortmannin affects the localization of Heat shock factor protein 1 (HSF1).	[21]

References

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• [11] Non-steroidal anti-inflammatory drugs inhibit the expression of cytokines and induce HSP70 in human monocytes. Cytokine. 1999 May;11(5):347-58. doi: 10.1006/cyto.1998.0437.
• [12] Enhanced protein denaturation in indomethacin-treated cells. Cell Stress Chaperones. 2000 Jan;5(1):8-13. doi: 10.1043/1355-8145(2000)005<0008:EPDIIT>2.0.CO;2.
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