Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTO1Y11)

• DOT Name: 60 kDa heat shock protein, mitochondrial (HSPD1)
• Synonyms: EC 5.6.1.7; 60 kDa chaperonin; Chaperonin 60; CPN60; Heat shock protein 60; HSP-60; Hsp60; HuCHA60; Mitochondrial matrix protein P1; P60 lymphocyte protein
• Gene Name: HSPD1
• Related Disease:
  Hereditary spastic paraplegia 13
  Hypomyelinating leukodystrophy 4
• UniProt ID: CH60_HUMAN
• PDB ID: 4PJ1; 6HT7; 6MRC; 6MRD; 7AZP; 7L7S; 8G7J; 8G7K; 8G7L; 8G7M; 8G7N; 8G7O
• EC Number: 5.6.1.7
• Pfam ID: PF00118
• Sequence:
  MLRLPTVFRQMRPVSRVLAPHLTRAYAKDVKFGADARALMLQGVDLLADAVAVTMGPKGR
  TVIIEQSWGSPKVTKDGVTVAKSIDLKDKYKNIGAKLVQDVANNTNEEAGDGTTTATVLA
  RSIAKEGFEKISKGANPVEIRRGVMLAVDAVIAELKKQSKPVTTPEEIAQVATISANGDK
  EIGNIISDAMKKVGRKGVITVKDGKTLNDELEIIEGMKFDRGYISPYFINTSKGQKCEFQ
  DAYVLLSEKKISSIQSIVPALEIANAHRKPLVIIAEDVDGEALSTLVLNRLKVGLQVVAV
  KAPGFGDNRKNQLKDMAIATGGAVFGEEGLTLNLEDVQPHDLGKVGEVIVTKDDAMLLKG
  KGDKAQIEKRIQEIIEQLDVTTSEYEKEKLNERLAKLSDGVAVLKVGGTSDVEVNEKKDR
  VTDALNATRAAVEEGIVLGGGCALLRCIPALDSLTPANEDQKIGIEIIKRTLKIPAMTIA
  KNAGVEGSLIVEKIMQSSSEVGYDAMAGDFVNMVEKGIIDPTKVVRTALLDAAGVASLLT
  TAEVVVTEIPKEEKDPGMGAMGGMGGGMGGGMF
• Function: Chaperonin implicated in mitochondrial protein import and macromolecular assembly. Together with Hsp10, facilitates the correct folding of imported proteins. May also prevent misfolding and promote the refolding and proper assembly of unfolded polypeptides generated under stress conditions in the mitochondrial matrix. The functional units of these chaperonins consist of heptameric rings of the large subunit Hsp60, which function as a back-to-back double ring. In a cyclic reaction, Hsp60 ring complexes bind one unfolded substrate protein per ring, followed by the binding of ATP and association with 2 heptameric rings of the co-chaperonin Hsp10. This leads to sequestration of the substrate protein in the inner cavity of Hsp60 where, for a certain period of time, it can fold undisturbed by other cell components. Synchronous hydrolysis of ATP in all Hsp60 subunits results in the dissociation of the chaperonin rings and the release of ADP and the folded substrate protein (Probable).
• KEGG Pathway:
  R. degradation (hsa03018)
  Type I diabetes mellitus (hsa04940)
  Legionellosis (hsa05134)
  Tuberculosis (hsa05152)
  Lipid and atherosclerosis (hsa05417)
• Reactome Pathway:
  TFAP2A acts as a transcriptional repressor during retinoic acid induced cell differentiation (R-HSA-8869496)
  Mitochondrial protein import (R-HSA-1268020)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hereditary spastic paraplegia 13	DISBNUNW	Strong	Autosomal dominant	[1]
Hypomyelinating leukodystrophy 4	DISLDO8X	Strong	Autosomal recessive	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Sulforaphane	DMQY3L0	Investigative	60 kDa heat shock protein, mitochondrial (HSPD1) affects the binding of Sulforaphane.	[46]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of 60 kDa heat shock protein, mitochondrial (HSPD1).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of 60 kDa heat shock protein, mitochondrial (HSPD1).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of 60 kDa heat shock protein, mitochondrial (HSPD1).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of 60 kDa heat shock protein, mitochondrial (HSPD1).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of 60 kDa heat shock protein, mitochondrial (HSPD1).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of 60 kDa heat shock protein, mitochondrial (HSPD1).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of 60 kDa heat shock protein, mitochondrial (HSPD1).	[9]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of 60 kDa heat shock protein, mitochondrial (HSPD1).	[10]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of 60 kDa heat shock protein, mitochondrial (HSPD1).	[11]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of 60 kDa heat shock protein, mitochondrial (HSPD1).	[12]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of 60 kDa heat shock protein, mitochondrial (HSPD1).	[4]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of 60 kDa heat shock protein, mitochondrial (HSPD1).	[13]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of 60 kDa heat shock protein, mitochondrial (HSPD1).	[14]
Marinol	DM70IK5	Approved	Marinol increases the expression of 60 kDa heat shock protein, mitochondrial (HSPD1).	[15]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of 60 kDa heat shock protein, mitochondrial (HSPD1).	[16]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of 60 kDa heat shock protein, mitochondrial (HSPD1).	[17]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of 60 kDa heat shock protein, mitochondrial (HSPD1).	[18]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of 60 kDa heat shock protein, mitochondrial (HSPD1).	[19]
Cocaine	DMSOX7I	Approved	Cocaine affects the expression of 60 kDa heat shock protein, mitochondrial (HSPD1).	[20]
Zidovudine	DM4KI7O	Approved	Zidovudine affects the expression of 60 kDa heat shock protein, mitochondrial (HSPD1).	[21]
Acocantherin	DM7JT24	Approved	Acocantherin affects the expression of 60 kDa heat shock protein, mitochondrial (HSPD1).	[22]
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial increases the expression of 60 kDa heat shock protein, mitochondrial (HSPD1).	[23]
Motexafin gadolinium	DMEJKRF	Approved	Motexafin gadolinium increases the expression of 60 kDa heat shock protein, mitochondrial (HSPD1).	[23]
Etretinate	DM2CZFA	Approved	Etretinate decreases the expression of 60 kDa heat shock protein, mitochondrial (HSPD1).	[24]
Dihydroxyacetone	DMM1LG2	Approved	Dihydroxyacetone increases the expression of 60 kDa heat shock protein, mitochondrial (HSPD1).	[25]
Gallium nitrate	DMF9O6B	Approved	Gallium nitrate decreases the expression of 60 kDa heat shock protein, mitochondrial (HSPD1).	[26]
Stavudine	DM6DEK9	Approved	Stavudine affects the expression of 60 kDa heat shock protein, mitochondrial (HSPD1).	[21]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of 60 kDa heat shock protein, mitochondrial (HSPD1).	[27]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene decreases the expression of 60 kDa heat shock protein, mitochondrial (HSPD1).	[16]
ACYLINE	DM9GRTK	Phase 2	ACYLINE increases the expression of 60 kDa heat shock protein, mitochondrial (HSPD1).	[29]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of 60 kDa heat shock protein, mitochondrial (HSPD1).	[30]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of 60 kDa heat shock protein, mitochondrial (HSPD1).	[31]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of 60 kDa heat shock protein, mitochondrial (HSPD1).	[33]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of 60 kDa heat shock protein, mitochondrial (HSPD1).	[34]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of 60 kDa heat shock protein, mitochondrial (HSPD1).	[35]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of 60 kDa heat shock protein, mitochondrial (HSPD1).	[36]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of 60 kDa heat shock protein, mitochondrial (HSPD1).	[37]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of 60 kDa heat shock protein, mitochondrial (HSPD1).	[38]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of 60 kDa heat shock protein, mitochondrial (HSPD1).	[39]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of 60 kDa heat shock protein, mitochondrial (HSPD1).	[40]
D-glucose	DMMG2TO	Investigative	D-glucose decreases the expression of 60 kDa heat shock protein, mitochondrial (HSPD1).	[41]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine decreases the expression of 60 kDa heat shock protein, mitochondrial (HSPD1).	[42]
Rutin	DMEHRAJ	Investigative	Rutin decreases the expression of 60 kDa heat shock protein, mitochondrial (HSPD1).	[44]
Lead acetate	DML0GZ2	Investigative	Lead acetate decreases the expression of 60 kDa heat shock protein, mitochondrial (HSPD1).	[45]
CATECHIN	DMY38SB	Investigative	CATECHIN decreases the expression of 60 kDa heat shock protein, mitochondrial (HSPD1).	[44]
Flavone	DMEQH6J	Investigative	Flavone decreases the expression of 60 kDa heat shock protein, mitochondrial (HSPD1).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of 60 kDa heat shock protein, mitochondrial (HSPD1).	[28]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal affects the binding of 60 kDa heat shock protein, mitochondrial (HSPD1).	[43]

1 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 increases the phosphorylation of 60 kDa heat shock protein, mitochondrial (HSPD1).	[32]

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