Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5HR0AR)

• DOT Name: Heat shock 70 kDa protein 4 (HSPA4)
• Synonyms: HSP70RY; Heat shock 70-related protein APG-2
• Gene Name: HSPA4
• Related Disease:
  Autoimmune disease
  Bipolar disorder
  High blood pressure
  Metastatic malignant neoplasm
  Multiple sclerosis
  Type-1/2 diabetes
  Adult glioblastoma
  Adult respiratory distress syndrome
  Alzheimer disease
  Asthma
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Cardiac failure
  Castration-resistant prostate carcinoma
  Cerebral infarction
  Chronic obstructive pulmonary disease
  Colorectal carcinoma
  Congestive heart failure
  facioscapulohumeral muscular dystrophy
  Gastric cancer
  Glioblastoma multiforme
  Glioma
  Hepatocellular carcinoma
  Huntington disease
  Liver and intrahepatic bile duct neoplasm
  Lung cancer
  Lung carcinoma
  Malaria
  Melanoma
  Mood disorder
  Non-insulin dependent diabetes
  Non-small-cell lung cancer
  Parkinson disease
  Prostate cancer
  Prostate carcinoma
  Stomach cancer
  Tuberculosis
  Urinary bladder cancer
  Visceral leishmaniasis
  Bone osteosarcoma
  Colon carcinoma
  Osteosarcoma
  Leishmaniasis
  Arteriosclerosis
  Atherosclerosis
  Neuroblastoma
• UniProt ID: HSP74_HUMAN
• Pfam ID: PF00012
• Sequence:
  MSVVGIDLGFQSCYVAVARAGGIETIANEYSDRCTPACISFGPKNRSIGAAAKSQVISNA
  KNTVQGFKRFHGRAFSDPFVEAEKSNLAYDIVQLPTGLTGIKVTYMEEERNFTTEQVTAM
  LLSKLKETAESVLKKPVVDCVVSVPCFYTDAERRSVMDATQIAGLNCLRLMNETTAVALA
  YGIYKQDLPALEEKPRNVVFVDMGHSAYQVSVCAFNRGKLKVLATAFDTTLGGRKFDEVL
  VNHFCEEFGKKYKLDIKSKIRALLRLSQECEKLKKLMSANASDLPLSIECFMNDVDVSGT
  MNRGKFLEMCNDLLARVEPPLRSVLEQTKLKKEDIYAVEIVGGATRIPAVKEKISKFFGK
  ELSTTLNADEAVTRGCALQCAILSPAFKVREFSITDVVPYPISLRWNSPAEEGSSDCEVF
  SKNHAAPFSKVLTFYRKEPFTLEAYYSSPQDLPYPDPAIAQFSVQKVTPQSDGSSSKVKV
  KVRVNVHGIFSVSSASLVEVHKSEENEEPMETDQNAKEEEKMQVDQEEPHVEEQQQQTPA
  ENKAESEEMETSQAGSKDKKMDQPPQAKKAKVKTSTVDLPIENQLLWQIDREMLNLYIEN
  EGKMIMQDKLEKERNDAKNAVEEYVYEMRDKLSGEYEKFVSEDDRNSFTLKLEDTENWLY
  EDGEDQPKQVYVDKLAELKNLGQPIKIRFQESEERPKLFEELGKQIQQYMKIISSFKNKE
  DQYDHLDAADMTKVEKSTNEAMEWMNNKLNLQNKQSLTMDPVVKSKEIEAKIKELTSTCS
  PIISKPKPKVEPPKEEQKNAEQNGPVDGQGDNPGPQAAEQGTDTAVPSDSDKKLPEMDID
• KEGG Pathway:
  Tight junction (hsa04530)
  Antigen processing and presentation (hsa04612)
  Lipid and atherosclerosis (hsa05417)
• Reactome Pathway: Regulation of HSF1-mediated heat shock response (R-HSA-3371453)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autoimmune disease	DISORMTM	Definitive	Biomarker	[1]
Bipolar disorder	DISAM7J2	Definitive	Altered Expression	[2]
High blood pressure	DISY2OHH	Definitive	Biomarker	[1]
Metastatic malignant neoplasm	DIS86UK6	Definitive	Biomarker	[3]
Multiple sclerosis	DISB2WZI	Definitive	Genetic Variation	[4]
Type-1/2 diabetes	DISIUHAP	Definitive	Altered Expression	[5]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[6]
Adult respiratory distress syndrome	DISIJV47	Strong	Biomarker	[7]
Alzheimer disease	DISF8S70	Strong	Biomarker	[8]
Asthma	DISW9QNS	Strong	Biomarker	[9]
Breast cancer	DIS7DPX1	Strong	Biomarker	[10]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[10]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[11]
Cardiac failure	DISDC067	Strong	Altered Expression	[12]
Castration-resistant prostate carcinoma	DISVGAE6	Strong	Biomarker	[13]
Cerebral infarction	DISR1WNP	Strong	Biomarker	[14]
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Genetic Variation	[15]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[16]
Congestive heart failure	DIS32MEA	Strong	Altered Expression	[12]
facioscapulohumeral muscular dystrophy	DISSE0H0	Strong	Biomarker	[17]
Gastric cancer	DISXGOUK	Strong	Biomarker	[18]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[6]
Glioma	DIS5RPEH	Strong	Altered Expression	[19]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[20]
Huntington disease	DISQPLA4	Strong	Biomarker	[21]
Liver and intrahepatic bile duct neoplasm	DISRQ76N	Strong	Biomarker	[22]
Lung cancer	DISCM4YA	Strong	Altered Expression	[23]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[23]
Malaria	DISQ9Y50	Strong	Biomarker	[24]
Melanoma	DIS1RRCY	Strong	Biomarker	[25]
Mood disorder	DISLVMWO	Strong	Biomarker	[26]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[27]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[6]
Parkinson disease	DISQVHKL	Strong	Altered Expression	[28]
Prostate cancer	DISF190Y	Strong	Altered Expression	[29]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[29]
Stomach cancer	DISKIJSX	Strong	Biomarker	[18]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[30]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[31]
Visceral leishmaniasis	DISTKEYK	Strong	Biomarker	[32]
Bone osteosarcoma	DIST1004	moderate	Biomarker	[33]
Colon carcinoma	DISJYKUO	moderate	Biomarker	[34]
Osteosarcoma	DISLQ7E2	moderate	Biomarker	[33]
Leishmaniasis	DISABTW7	Disputed	Biomarker	[35]
Arteriosclerosis	DISK5QGC	Limited	Biomarker	[36]
Atherosclerosis	DISMN9J3	Limited	Biomarker	[36]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[37]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
PEITC	DMOMN31	Phase 2	Heat shock 70 kDa protein 4 (HSPA4) affects the binding of PEITC.	[66]
Sulforaphane	DMQY3L0	Investigative	Heat shock 70 kDa protein 4 (HSPA4) affects the binding of Sulforaphane.	[66]

31 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 70 kDa protein 4 (HSPA4).	[38]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Heat shock 70 kDa protein 4 (HSPA4).	[39]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Heat shock 70 kDa protein 4 (HSPA4).	[40]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Heat shock 70 kDa protein 4 (HSPA4).	[41]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Heat shock 70 kDa protein 4 (HSPA4).	[42]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Heat shock 70 kDa protein 4 (HSPA4).	[43]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Heat shock 70 kDa protein 4 (HSPA4).	[44]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Heat shock 70 kDa protein 4 (HSPA4).	[45]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Heat shock 70 kDa protein 4 (HSPA4).	[46]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Heat shock 70 kDa protein 4 (HSPA4).	[47]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Heat shock 70 kDa protein 4 (HSPA4).	[48]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Heat shock 70 kDa protein 4 (HSPA4).	[42]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Heat shock 70 kDa protein 4 (HSPA4).	[49]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Heat shock 70 kDa protein 4 (HSPA4).	[50]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Heat shock 70 kDa protein 4 (HSPA4).	[51]
Simvastatin	DM30SGU	Approved	Simvastatin increases the expression of Heat shock 70 kDa protein 4 (HSPA4).	[52]
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial increases the expression of Heat shock 70 kDa protein 4 (HSPA4).	[53]
Motexafin gadolinium	DMEJKRF	Approved	Motexafin gadolinium increases the expression of Heat shock 70 kDa protein 4 (HSPA4).	[53]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Heat shock 70 kDa protein 4 (HSPA4).	[54]
Curcumin	DMQPH29	Phase 3	Curcumin increases the expression of Heat shock 70 kDa protein 4 (HSPA4).	[55]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Heat shock 70 kDa protein 4 (HSPA4).	[56]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene decreases the expression of Heat shock 70 kDa protein 4 (HSPA4).	[42]
Tanespimycin	DMNLQHK	Phase 2	Tanespimycin increases the expression of Heat shock 70 kDa protein 4 (HSPA4).	[57]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the expression of Heat shock 70 kDa protein 4 (HSPA4).	[54]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Heat shock 70 kDa protein 4 (HSPA4).	[59]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Heat shock 70 kDa protein 4 (HSPA4).	[60]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Heat shock 70 kDa protein 4 (HSPA4).	[61]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Heat shock 70 kDa protein 4 (HSPA4).	[62]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Heat shock 70 kDa protein 4 (HSPA4).	[63]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Heat shock 70 kDa protein 4 (HSPA4).	[64]
Linalool	DMGZQ5P	Investigative	Linalool increases the expression of Heat shock 70 kDa protein 4 (HSPA4).	[65]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Heat shock 70 kDa protein 4 (HSPA4).	[58]

References

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