Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT181WZB)

• DOT Name: Heat shock 70 kDa protein 4L (HSPA4L)
• Synonyms: Heat shock 70-related protein APG-1; Heat-shock protein family A member 4-like protein; HSPA4-like protein; Osmotic stress protein 94
• Gene Name: HSPA4L
• Related Disease:
  leukaemia
  Leukemia
  Male infertility
  Testicular germ cell tumor
  Nasopharyngeal carcinoma
  Periodontitis
• UniProt ID: HS74L_HUMAN
• Pfam ID: PF00012
• Sequence:
  MSVVGIDLGFLNCYIAVARSGGIETIANEYSDRCTPACISLGSRTRAIGNAAKSQIVTNV
  RNTIHGFKKLHGRSFDDPIVQTERIRLPYELQKMPNGSAGVKVRYLEEERPFAIEQVTGM
  LLAKLKETSENALKKPVADCVISIPSFFTDAERRSVMAAAQVAGLNCLRLMNETTAVALA
  YGIYKQDLPPLDEKPRNVVFIDMGHSAYQVLVCAFNKGKLKVLATTFDPYLGGRNFDEAL
  VDYFCDEFKTKYKINVKENSRALLRLYQECEKLKKLMSANASDLPLNIECFMNDLDVSSK
  MNRAQFEQLCASLLARVEPPLKAVMEQANLQREDISSIEIVGGATRIPAVKEQITKFFLK
  DISTTLNADEAVARGCALQCAILSPAFKVREFSITDLVPYSITLRWKTSFEDGSGECEVF
  CKNHPAPFSKVITFHKKEPFELEAFYTNLHEVPYPDARIGSFTIQNVFPQSDGDSSKVKV
  KVRVNIHGIFSVASASVIEKQNLEGDHSDAPMETETSFKNENKDNMDKMQVDQEEGHQKC
  HAEHTPEEEIDHTGAKTKSAVSDKQDRLNQTLKKGKVKSIDLPIQSSLCRQLGQDLLNSY
  IENEGKMIMQDKLEKERNDAKNAVEEYVYDFRDRLGTVYEKFITPEDLSKLSAVLEDTEN
  WLYEDGEDQPKQVYVDKLQELKKYGQPIQMKYMEHEERPKALNDLGKKIQLVMKVIEAYR
  NKDERYDHLDPTEMEKVEKCISDAMSWLNSKMNAQNKLSLTQDPVVKVSEIVAKSKELDN
  FCNPIIYKPKPKAEVPEDKPKANSEHNGPMDGQSGTETKSDSTKDSSQHTKSSGEMEVD
• Function: Possesses chaperone activity in vitro where it inhibits aggregation of citrate synthase.
• KEGG Pathway: Protein processing in endoplasmic reticulum (hsa04141)
• Reactome Pathway: Regulation of HSF1-mediated heat shock response (R-HSA-3371453)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
leukaemia	DISS7D1V	Strong	Altered Expression	[1]
Leukemia	DISNAKFL	Strong	Altered Expression	[1]
Male infertility	DISY3YZZ	Strong	Biomarker	[2]
Testicular germ cell tumor	DIS5RN24	Strong	Biomarker	[3]
Nasopharyngeal carcinoma	DISAOTQ0	moderate	Altered Expression	[4]
Periodontitis	DISI9JOI	Limited	Biomarker	[5]

30 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 4L (HSPA4L).	[6]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Heat shock 70 kDa protein 4L (HSPA4L).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Heat shock 70 kDa protein 4L (HSPA4L).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Heat shock 70 kDa protein 4L (HSPA4L).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Heat shock 70 kDa protein 4L (HSPA4L).	[10]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Heat shock 70 kDa protein 4L (HSPA4L).	[11]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Heat shock 70 kDa protein 4L (HSPA4L).	[12]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Heat shock 70 kDa protein 4L (HSPA4L).	[13]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Heat shock 70 kDa protein 4L (HSPA4L).	[14]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Heat shock 70 kDa protein 4L (HSPA4L).	[15]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Heat shock 70 kDa protein 4L (HSPA4L).	[16]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Heat shock 70 kDa protein 4L (HSPA4L).	[17]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Heat shock 70 kDa protein 4L (HSPA4L).	[18]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Heat shock 70 kDa protein 4L (HSPA4L).	[19]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Heat shock 70 kDa protein 4L (HSPA4L).	[20]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Heat shock 70 kDa protein 4L (HSPA4L).	[21]
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial increases the expression of Heat shock 70 kDa protein 4L (HSPA4L).	[22]
Motexafin gadolinium	DMEJKRF	Approved	Motexafin gadolinium increases the expression of Heat shock 70 kDa protein 4L (HSPA4L).	[22]
Sodium phenylbutyrate	DMXLBCQ	Approved	Sodium phenylbutyrate increases the expression of Heat shock 70 kDa protein 4L (HSPA4L).	[23]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Heat shock 70 kDa protein 4L (HSPA4L).	[24]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Heat shock 70 kDa protein 4L (HSPA4L).	[19]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Heat shock 70 kDa protein 4L (HSPA4L).	[25]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of Heat shock 70 kDa protein 4L (HSPA4L).	[26]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Heat shock 70 kDa protein 4L (HSPA4L).	[12]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Heat shock 70 kDa protein 4L (HSPA4L).	[27]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Heat shock 70 kDa protein 4L (HSPA4L).	[28]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Heat shock 70 kDa protein 4L (HSPA4L).	[30]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Heat shock 70 kDa protein 4L (HSPA4L).	[31]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Heat shock 70 kDa protein 4L (HSPA4L).	[32]
Resorcinol	DMM37C0	Investigative	Resorcinol decreases the expression of Heat shock 70 kDa protein 4L (HSPA4L).	[33]

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 70 kDa protein 4L (HSPA4L).	[29]

References

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• [20] Chronic ethanol exposure increases goosecoid (GSC) expression in human embryonic carcinoma cell differentiation. J Appl Toxicol. 2014 Jan;34(1):66-75.
• [21] In vitro and in vivo irinotecan-induced changes in expression profiles of cell cycle and apoptosis-associated genes in acute myeloid leukemia cells. Mol Cancer Ther. 2005 Jun;4(6):885-900.
• [22] Motexafin gadolinium and zinc induce oxidative stress responses and apoptosis in B-cell lymphoma lines. Cancer Res. 2005 Dec 15;65(24):11676-88.
• [23] Gene expression profile analysis of 4-phenylbutyrate treatment of IB3-1 bronchial epithelial cell line demonstrates a major influence on heat-shock proteins. Physiol Genomics. 2004 Jan 15;16(2):204-11.
• [24] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
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