Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSDET7B)

• DOT Name: Heat shock-related 70 kDa protein 2 (HSPA2)
• Synonyms: Heat shock 70 kDa protein 2
• Gene Name: HSPA2
• Related Disease:
  Adenocarcinoma
  Agranulocytosis
  Alzheimer disease
  Arteriosclerosis
  Atherosclerosis
  Autoimmune disease
  Azoospermia
  Bladder cancer
  Bladder transitional cell carcinoma
  Breast cancer
  Carcinoma
  Cardiovascular disease
  Carotid stenosis
  Clear cell renal carcinoma
  Colon cancer
  Colonic neoplasm
  Colorectal carcinoma
  Coronary heart disease
  Epithelial ovarian cancer
  Esophageal squamous cell carcinoma
  Gastric cancer
  Graves disease
  Hepatocellular carcinoma
  Lung cancer
  Lung carcinoma
  Male infertility
  Multiple sclerosis
  Myocardial ischemia
  Nasopharyngeal carcinoma
  Neoplasm
  Non-small-cell lung cancer
  Ovarian cancer
  Ovarian neoplasm
  Prostate cancer
  Prostate carcinoma
  Renal cell carcinoma
  Stomach cancer
  Urinary bladder cancer
  Urinary bladder neoplasm
  Breast carcinoma
  High blood pressure
  Non-insulin dependent diabetes
  Type-1/2 diabetes
  Coronary atherosclerosis
  Neuroblastoma
  Pancreatic cancer
  Type-1 diabetes
• UniProt ID: HSP72_HUMAN
• PDB ID: 3I33; 4FSV; 5FPD; 5FPE; 5FPM; 5FPN
• Pfam ID: PF00012
• Sequence:
  MSARGPAIGIDLGTTYSCVGVFQHGKVEIIANDQGNRTTPSYVAFTDTERLIGDAAKNQV
  AMNPTNTIFDAKRLIGRKFEDATVQSDMKHWPFRVVSEGGKPKVQVEYKGETKTFFPEEI
  SSMVLTKMKEIAEAYLGGKVHSAVITVPAYFNDSQRQATKDAGTITGLNVLRIINEPTAA
  AIAYGLDKKGCAGGEKNVLIFDLGGGTFDVSILTIEDGIFEVKSTAGDTHLGGEDFDNRM
  VSHLAEEFKRKHKKDIGPNKRAVRRLRTACERAKRTLSSSTQASIEIDSLYEGVDFYTSI
  TRARFEELNADLFRGTLEPVEKALRDAKLDKGQIQEIVLVGGSTRIPKIQKLLQDFFNGK
  ELNKSINPDEAVAYGAAVQAAILIGDKSENVQDLLLLDVTPLSLGIETAGGVMTPLIKRN
  TTIPTKQTQTFTTYSDNQSSVLVQVYEGERAMTKDNNLLGKFDLTGIPPAPRGVPQIEVT
  FDIDANGILNVTAADKSTGKENKITITNDKGRLSKDDIDRMVQEAERYKSEDEANRDRVA
  AKNALESYTYNIKQTVEDEKLRGKISEQDKNKILDKCQEVINWLDRNQMAEKDEYEHKQK
  ELERVCNPIISKLYQGGPGGGSGGGGSGASGGPTIEEVD
• Function: Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteolysis of misfolded proteins and the formation and dissociation of protein complexes. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation. This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones. The affinity for polypeptides is regulated by its nucleotide bound state. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. It goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release. Plays a role in spermatogenesis. In association with SHCBP1L may participate in the maintenance of spindle integrity during meiosis in male germ cells.
• KEGG Pathway:
  Antigen processing and presentation (hsa04612)
  Lipid and atherosclerosis (hsa05417)
• Reactome Pathway:
  Regulation of HSF1-mediated heat shock response (R-HSA-3371453)
  HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand (R-HSA-3371497)
  Attenuation phase (R-HSA-3371568)
  PKR-mediated signaling (R-HSA-9833482)
  Meiotic synapsis (R-HSA-1221632)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[1]
Agranulocytosis	DISJS4LS	Strong	Genetic Variation	[2]
Alzheimer disease	DISF8S70	Strong	Biomarker	[3]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[4]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[4]
Autoimmune disease	DISORMTM	Strong	Genetic Variation	[5]
Azoospermia	DIS94181	Strong	Biomarker	[6]
Bladder cancer	DISUHNM0	Strong	Biomarker	[7]
Bladder transitional cell carcinoma	DISNL46A	Strong	Biomarker	[8]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[9]
Carcinoma	DISH9F1N	Strong	Biomarker	[10]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[11]
Carotid stenosis	DISZA8D0	Strong	Genetic Variation	[12]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[13]
Colon cancer	DISVC52G	Strong	Biomarker	[14]
Colonic neoplasm	DISSZ04P	Strong	Biomarker	[14]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[8]
Coronary heart disease	DIS5OIP1	Strong	Genetic Variation	[15]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[1]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[16]
Gastric cancer	DISXGOUK	Strong	Genetic Variation	[17]
Graves disease	DISU4KOQ	Strong	Genetic Variation	[18]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[19]
Lung cancer	DISCM4YA	Strong	Biomarker	[20]
Lung carcinoma	DISTR26C	Strong	Biomarker	[20]
Male infertility	DISY3YZZ	Strong	Altered Expression	[21]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[22]
Myocardial ischemia	DISFTVXF	Strong	Biomarker	[23]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Altered Expression	[24]
Neoplasm	DISZKGEW	Strong	Altered Expression	[9]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[25]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[1]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[1]
Prostate cancer	DISF190Y	Strong	Biomarker	[26]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[26]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[13]
Stomach cancer	DISKIJSX	Strong	Genetic Variation	[17]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[7]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[7]
Breast carcinoma	DIS2UE88	moderate	Altered Expression	[9]
High blood pressure	DISY2OHH	moderate	Genetic Variation	[27]
Non-insulin dependent diabetes	DISK1O5Z	moderate	Genetic Variation	[11]
Type-1/2 diabetes	DISIUHAP	moderate	Genetic Variation	[28]
Coronary atherosclerosis	DISKNDYU	Limited	Biomarker	[15]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[29]
Pancreatic cancer	DISJC981	Limited	Altered Expression	[30]
Type-1 diabetes	DIS7HLUB	Limited	Genetic Variation	[31]

This DOT Affected the Drug Response of 4 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	Heat shock-related 70 kDa protein 2 (HSPA2) affects the response to substance of Etoposide.	[76]
Topotecan	DMP6G8T	Approved	Heat shock-related 70 kDa protein 2 (HSPA2) affects the response to substance of Topotecan.	[76]
Mitoxantrone	DMM39BF	Approved	Heat shock-related 70 kDa protein 2 (HSPA2) affects the response to substance of Mitoxantrone.	[76]
Cyclophosphamide	DM4O2Z7	Approved	Heat shock-related 70 kDa protein 2 (HSPA2) affects the response to substance of Cyclophosphamide.	[76]

42 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-related 70 kDa protein 2 (HSPA2).	[32]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Heat shock-related 70 kDa protein 2 (HSPA2).	[33]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Heat shock-related 70 kDa protein 2 (HSPA2).	[34]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Heat shock-related 70 kDa protein 2 (HSPA2).	[35]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Heat shock-related 70 kDa protein 2 (HSPA2).	[36]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Heat shock-related 70 kDa protein 2 (HSPA2).	[37]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Heat shock-related 70 kDa protein 2 (HSPA2).	[38]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Heat shock-related 70 kDa protein 2 (HSPA2).	[39]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Heat shock-related 70 kDa protein 2 (HSPA2).	[40]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Heat shock-related 70 kDa protein 2 (HSPA2).	[41]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Heat shock-related 70 kDa protein 2 (HSPA2).	[42]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Heat shock-related 70 kDa protein 2 (HSPA2).	[43]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Heat shock-related 70 kDa protein 2 (HSPA2).	[44]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Heat shock-related 70 kDa protein 2 (HSPA2).	[45]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Heat shock-related 70 kDa protein 2 (HSPA2).	[46]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Heat shock-related 70 kDa protein 2 (HSPA2).	[47]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Heat shock-related 70 kDa protein 2 (HSPA2).	[48]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Heat shock-related 70 kDa protein 2 (HSPA2).	[49]
Amphotericin B	DMTAJQE	Approved	Amphotericin B decreases the expression of Heat shock-related 70 kDa protein 2 (HSPA2).	[50]
Sodium phenylbutyrate	DMXLBCQ	Approved	Sodium phenylbutyrate increases the expression of Heat shock-related 70 kDa protein 2 (HSPA2).	[51]
Isoproterenol	DMK7MEY	Approved	Isoproterenol increases the expression of Heat shock-related 70 kDa protein 2 (HSPA2).	[52]
Dihydroxyacetone	DMM1LG2	Approved	Dihydroxyacetone increases the expression of Heat shock-related 70 kDa protein 2 (HSPA2).	[53]
Penicillamine	DM40EF6	Approved	Penicillamine increases the expression of Heat shock-related 70 kDa protein 2 (HSPA2).	[54]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Heat shock-related 70 kDa protein 2 (HSPA2).	[55]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Heat shock-related 70 kDa protein 2 (HSPA2).	[56]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Heat shock-related 70 kDa protein 2 (HSPA2).	[57]
Fenretinide	DMRD5SP	Phase 3	Fenretinide decreases the expression of Heat shock-related 70 kDa protein 2 (HSPA2).	[58]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Heat shock-related 70 kDa protein 2 (HSPA2).	[59]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene decreases the expression of Heat shock-related 70 kDa protein 2 (HSPA2).	[61]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Heat shock-related 70 kDa protein 2 (HSPA2).	[63]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Heat shock-related 70 kDa protein 2 (HSPA2).	[64]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 increases the expression of Heat shock-related 70 kDa protein 2 (HSPA2).	[65]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Heat shock-related 70 kDa protein 2 (HSPA2).	[66]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Heat shock-related 70 kDa protein 2 (HSPA2).	[67]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Heat shock-related 70 kDa protein 2 (HSPA2).	[68]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Heat shock-related 70 kDa protein 2 (HSPA2).	[69]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Heat shock-related 70 kDa protein 2 (HSPA2).	[70]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of Heat shock-related 70 kDa protein 2 (HSPA2).	[71]
geraniol	DMS3CBD	Investigative	geraniol decreases the expression of Heat shock-related 70 kDa protein 2 (HSPA2).	[72]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of Heat shock-related 70 kDa protein 2 (HSPA2).	[73]
Okadaic acid	DM47CO1	Investigative	Okadaic acid increases the expression of Heat shock-related 70 kDa protein 2 (HSPA2).	[74]
CH-223191	DMMJZYC	Investigative	CH-223191 decreases the expression of Heat shock-related 70 kDa protein 2 (HSPA2).	[75]

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-related 70 kDa protein 2 (HSPA2).	[60]

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 increases the methylation of Heat shock-related 70 kDa protein 2 (HSPA2).	[62]

References

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