Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVRR73T)

• DOT Name: Heat shock protein 105 kDa (HSPH1)
• Synonyms: Antigen NY-CO-25; Heat shock 110 kDa protein
• Gene Name: HSPH1
• Related Disease:
  Adenocarcinoma
  Adult lymphoma
  Advanced cancer
  Alzheimer disease
  B-cell lymphoma
  B-cell neoplasm
  Breast neoplasm
  Carcinoma of esophagus
  Clear cell renal carcinoma
  Colitis
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Colorectal neoplasm
  Coronary heart disease
  Esophageal cancer
  Esophageal squamous cell carcinoma
  Gastric cancer
  Hepatocellular carcinoma
  HIV infectious disease
  Immunodeficiency
  Lymphoma
  Lymphoma, non-Hodgkin, familial
  Neoplasm
  Neoplasm of esophagus
  Non-hodgkin lymphoma
  Pediatric lymphoma
  Renal cell carcinoma
  Tauopathy
  Gonorrhea
  Stomach cancer
  Age-related macular degeneration
  Breast cancer
  Breast carcinoma
  Colon adenocarcinoma
  Kennedy disease
  Melanoma
• UniProt ID: HS105_HUMAN
• PDB ID: 6GFA
• Pfam ID: PF00012
• Sequence:
  MSVVGLDVGSQSCYIAVARAGGIETIANEFSDRCTPSVISFGSKNRTIGVAAKNQQITHA
  NNTVSNFKRFHGRAFNDPFIQKEKENLSYDLVPLKNGGVGIKVMYMGEEHLFSVEQITAM
  LLTKLKETAENSLKKPVTDCVISVPSFFTDAERRSVLDAAQIVGLNCLRLMNDMTAVALN
  YGIYKQDLPSLDEKPRIVVFVDMGHSAFQVSACAFNKGKLKVLGTAFDPFLGGKNFDEKL
  VEHFCAEFKTKYKLDAKSKIRALLRLYQECEKLKKLMSSNSTDLPLNIECFMNDKDVSGK
  MNRSQFEELCAELLQKIEVPLYSLLEQTHLKVEDVSAVEIVGGATRIPAVKERIAKFFGK
  DISTTLNADEAVARGCALQCAILSPAFKVREFSVTDAVPFPISLIWNHDSEDTEGVHEVF
  SRNHAAPFSKVLTFLRRGPFELEAFYSDPQGVPYPEAKIGRFVVQNVSAQKDGEKSRVKV
  KVRVNTHGIFTISTASMVEKVPTEENEMSSEADMECLNQRPPENPDTDKNVQQDNSEAGT
  QPQVQTDAQQTSQSPPSPELTSEENKIPDADKANEKKVDQPPEAKKPKIKVVNVELPIEA
  NLVWQLGKDLLNMYIETEGKMIMQDKLEKERNDAKNAVEEYVYEFRDKLCGPYEKFICEQ
  DHQNFLRLLTETEDWLYEEGEDQAKQAYVDKLEELMKIGTPVKVRFQEAEERPKMFEELG
  QRLQHYAKIAADFRNKDEKYNHIDESEMKKVEKSVNEVMEWMNNVMNAQAKKSLDQDPVV
  RAQEIKTKIKELNNTCEPVVTQPKPKIESPKLERTPNGPNIDKKEEDLEDKNNFGAEPPH
  QNGECYPNEKNSVNMDLD
• Function: Acts as a nucleotide-exchange factor (NEF) for chaperone proteins HSPA1A and HSPA1B, promoting the release of ADP from HSPA1A/B thereby triggering client/substrate protein release. Prevents the aggregation of denatured proteins in cells under severe stress, on which the ATP levels decrease markedly. Inhibits HSPA8/HSC70 ATPase and chaperone activities.
• Tissue Specificity: Highly expressed in testis. Present at lower levels in most brain regions, except cerebellum. Overexpressed in cancer cells.
• KEGG Pathway: Protein processing in endoplasmic reticulum (hsa04141)
• Reactome Pathway:
  Regulation of HSF1-mediated heat shock response (R-HSA-3371453)
  Scavenging by Class F Receptors (R-HSA-3000484)

Molecular Interaction Atlas (MIA) of This DOT

37 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[1]
Adult lymphoma	DISK8IZR	Strong	Altered Expression	[2]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[3]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[4]
B-cell lymphoma	DISIH1YQ	Strong	Altered Expression	[5]
B-cell neoplasm	DISVY326	Strong	Altered Expression	[6]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[7]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[8]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[9]
Colitis	DISAF7DD	Strong	Genetic Variation	[10]
Colon cancer	DISVC52G	Strong	Altered Expression	[11]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[11]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[3]
Colorectal neoplasm	DISR1UCN	Strong	Genetic Variation	[12]
Coronary heart disease	DIS5OIP1	Strong	Biomarker	[13]
Esophageal cancer	DISGB2VN	Strong	Biomarker	[8]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[14]
Gastric cancer	DISXGOUK	Strong	Genetic Variation	[15]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[16]
HIV infectious disease	DISO97HC	Strong	Biomarker	[17]
Immunodeficiency	DIS093I0	Strong	Biomarker	[2]
Lymphoma	DISN6V4S	Strong	Altered Expression	[2]
Lymphoma, non-Hodgkin, familial	DISCXYIZ	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[8]
Neoplasm of esophagus	DISOLKAQ	Strong	Biomarker	[8]
Non-hodgkin lymphoma	DISS2Y8A	Strong	Biomarker	[2]
Pediatric lymphoma	DIS51BK2	Strong	Altered Expression	[2]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[9]
Tauopathy	DISY2IPA	Strong	Altered Expression	[4]
Gonorrhea	DISQ5AO6	moderate	Biomarker	[18]
Stomach cancer	DISKIJSX	moderate	Biomarker	[18]
Age-related macular degeneration	DIS0XS2C	Limited	Biomarker	[19]
Breast cancer	DIS7DPX1	Limited	Biomarker	[20]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[20]
Colon adenocarcinoma	DISDRE0J	Limited	Altered Expression	[21]
Kennedy disease	DISXZVM1	Limited	Altered Expression	[22]
Melanoma	DIS1RRCY	Limited	Biomarker	[20]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PEITC	DMOMN31	Phase 2	Heat shock protein 105 kDa (HSPH1) affects the binding of PEITC.	[52]

32 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 Heat shock protein 105 kDa (HSPH1).	[23]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Heat shock protein 105 kDa (HSPH1).	[24]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Heat shock protein 105 kDa (HSPH1).	[25]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Heat shock protein 105 kDa (HSPH1).	[26]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Heat shock protein 105 kDa (HSPH1).	[27]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Heat shock protein 105 kDa (HSPH1).	[28]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Heat shock protein 105 kDa (HSPH1).	[29]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Heat shock protein 105 kDa (HSPH1).	[30]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Heat shock protein 105 kDa (HSPH1).	[31]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Heat shock protein 105 kDa (HSPH1).	[32]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Heat shock protein 105 kDa (HSPH1).	[33]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Heat shock protein 105 kDa (HSPH1).	[34]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Heat shock protein 105 kDa (HSPH1).	[35]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Heat shock protein 105 kDa (HSPH1).	[36]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Heat shock protein 105 kDa (HSPH1).	[37]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide increases the expression of Heat shock protein 105 kDa (HSPH1).	[38]
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial increases the expression of Heat shock protein 105 kDa (HSPH1).	[39]
Thalidomide	DM70BU5	Approved	Thalidomide increases the expression of Heat shock protein 105 kDa (HSPH1).	[40]
Motexafin gadolinium	DMEJKRF	Approved	Motexafin gadolinium increases the expression of Heat shock protein 105 kDa (HSPH1).	[39]
Sodium phenylbutyrate	DMXLBCQ	Approved	Sodium phenylbutyrate increases the expression of Heat shock protein 105 kDa (HSPH1).	[41]
Ritonavir	DMU764S	Approved	Ritonavir increases the expression of Heat shock protein 105 kDa (HSPH1).	[42]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Heat shock protein 105 kDa (HSPH1).	[43]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Heat shock protein 105 kDa (HSPH1).	[38]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Heat shock protein 105 kDa (HSPH1).	[45]
Eugenol	DM7US1H	Patented	Eugenol increases the expression of Heat shock protein 105 kDa (HSPH1).	[37]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Heat shock protein 105 kDa (HSPH1).	[47]
Celastrol	DMWQIJX	Preclinical	Celastrol increases the expression of Heat shock protein 105 kDa (HSPH1).	[48]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Heat shock protein 105 kDa (HSPH1).	[49]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Heat shock protein 105 kDa (HSPH1).	[37]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Heat shock protein 105 kDa (HSPH1).	[50]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Heat shock protein 105 kDa (HSPH1).	[51]
cinnamaldehyde	DMZDUXG	Investigative	cinnamaldehyde increases the expression of Heat shock protein 105 kDa (HSPH1).	[37]

1 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 Heat shock protein 105 kDa (HSPH1).	[44]

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 decreases the phosphorylation of Heat shock protein 105 kDa (HSPH1).	[46]

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