Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJQL0I3)

• DOT Name: Hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1)
• Synonyms: Cardiovascular helix-loop-helix factor 2; CHF-2; Class B basic helix-loop-helix protein 31; bHLHb31; HES-related repressor protein 1; Hairy and enhancer of split-related protein 1; HESR-1; Hairy-related transcription factor 1; HRT-1; hHRT1
• Gene Name: HEY1
• Related Disease:
  Lung cancer
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Acute myelogenous leukaemia
  Adult glioblastoma
  Advanced cancer
  Anaplastic astrocytoma
  Astrocytoma
  Autism spectrum disorder
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Clear cell renal carcinoma
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Glioblastoma multiforme
  High blood pressure
  Leukemia
  Lung carcinoma
  Lung neoplasm
  Neoplasm
  Neuroblastoma
  Oligoastrocytoma
  Primitive neuroectodermal tumor
  Adenocarcinoma
  Bone osteosarcoma
  Hepatocellular carcinoma
  Osteosarcoma
• UniProt ID: HEY1_HUMAN
• PDB ID: 2DB7
• Pfam ID: PF07527 ; PF00010
• Sequence:
  MKRAHPEYSSSDSELDETIEVEKESADENGNLSSALGSMSPTTSSQILARKRRRGIIEKR
  RRDRINNSLSELRRLVPSAFEKQGSAKLEKAEILQMTVDHLKMLHTAGGKGYFDAHALAM
  DYRSLGFRECLAEVARYLSIIEGLDASDPLRVRLVSHLNNYASQREAASGAHAGLGHIPW
  GTVFGHHPHIAHPLLLPQNGHGNAGTTASPTEPHHQGRLGSAHPEAPALRAPPSGSLGPV
  LPVVTSASKLSPPLLSSVASLSAFPFSFGSFHLLSPNALSPSAPTQAANLGKPYRPWGTE
  IGAF
• Function: Transcriptional repressor which binds preferentially to the canonical E box sequence 5'-CACGTG-3'. Downstream effector of Notch signaling required for cardiovascular development. Specifically required for the Notch-induced endocardial epithelial to mesenchymal transition, which is itself criticial for cardiac valve and septum development. May be required in conjunction with HEY2 to specify arterial cell fate or identity. Promotes maintenance of neuronal precursor cells and glial versus neuronal fate specification. Represses transcription by the cardiac transcriptional activators GATA4 and GATA6 and by the neuronal bHLH factors ASCL1/MASH1 and NEUROD4/MATH3. Involved in the regulation of liver cancer cells self-renewal.
• Tissue Specificity: Expressed in the somitic mesoderm, the central nervous system, the kidney, the heart, nasal epithelium, and limbs.
• KEGG Pathway:
  Notch sig.ling pathway (hsa04330)
  Human papillomavirus infection (hsa05165)
  Pathways in cancer (hsa05200)
  Breast cancer (hsa05224)
• Reactome Pathway:
  Constitutive Signaling by NOTCH1 PEST Domain Mutants (R-HSA-2644606)
  Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants (R-HSA-2894862)
  RUNX2 regulates osteoblast differentiation (R-HSA-8940973)
  NOTCH3 Intracellular Domain Regulates Transcription (R-HSA-9013508)
  NOTCH4 Intracellular Domain Regulates Transcription (R-HSA-9013695)
  Cardiogenesis (R-HSA-9733709)
  NOTCH1 Intracellular Domain Regulates Transcription (R-HSA-2122947)

Molecular Interaction Atlas (MIA) of This DOT

30 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung cancer	DISCM4YA	Definitive	Altered Expression	[1]
Prostate cancer	DISF190Y	Definitive	Biomarker	[2]
Prostate carcinoma	DISMJPLE	Definitive	Biomarker	[2]
Prostate neoplasm	DISHDKGQ	Definitive	Altered Expression	[2]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[3]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[4]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[5]
Anaplastic astrocytoma	DISSBE0K	Strong	Biomarker	[6]
Astrocytoma	DISL3V18	Strong	Biomarker	[6]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[7]
Breast cancer	DIS7DPX1	Strong	Biomarker	[8]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[8]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[8]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[9]
Colon cancer	DISVC52G	Strong	Altered Expression	[10]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[10]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[11]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[4]
High blood pressure	DISY2OHH	Strong	Biomarker	[12]
Leukemia	DISNAKFL	Strong	Biomarker	[13]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[1]
Lung neoplasm	DISVARNB	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Altered Expression	[14]
Neuroblastoma	DISVZBI4	Strong	Altered Expression	[15]
Oligoastrocytoma	DISQGE8F	Strong	Biomarker	[6]
Primitive neuroectodermal tumor	DISFHXHA	Strong	Biomarker	[6]
Adenocarcinoma	DIS3IHTY	moderate	Altered Expression	[16]
Bone osteosarcoma	DIST1004	moderate	Biomarker	[17]
Hepatocellular carcinoma	DIS0J828	moderate	Altered Expression	[18]
Osteosarcoma	DISLQ7E2	moderate	Biomarker	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Mitomycin	DMH0ZJE	Approved	Hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1) affects the response to substance of Mitomycin.	[47]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1).	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1).	[20]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1).	[21]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1).	[22]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1).	[23]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1).	[24]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1).	[25]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1).	[26]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1).	[27]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1).	[28]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1).	[29]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1).	[28]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1).	[30]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1).	[31]
Acocantherin	DM7JT24	Approved	Acocantherin increases the expression of Hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1).	[32]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1).	[33]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1).	[34]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1).	[35]
BAICALEIN	DM4C7E6	Phase 2	BAICALEIN increases the expression of Hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1).	[36]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1).	[37]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1).	[38]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1).	[39]
GSK2816126	DMJDVW4	Phase 1	GSK2816126 increases the expression of Hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1).	[40]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1).	[41]
Tacedinaline	DM1Z74X	Discontinued in Phase 2	Tacedinaline increases the expression of Hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1).	[28]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1).	[42]
Baicalin	DMY1TLZ	Terminated	Baicalin increases the expression of Hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1).	[36]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1).	[43]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1).	[44]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1).	[45]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE decreases the expression of Hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1).	[46]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid increases the expression of Hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1).	[28]

References

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