Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY9GJ1Y)

• DOT Name: Class E basic helix-loop-helix protein 41 (BHLHE41)
• Synonyms: bHLHe41; Class B basic helix-loop-helix protein 3; bHLHb3; Differentially expressed in chondrocytes protein 2; hDEC2; Enhancer-of-split and hairy-related protein 1; SHARP-1
• Gene Name: BHLHE41
• Related Disease:
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Pancreatic cancer
  Acute myelogenous leukaemia
  Adult glioblastoma
  Alveolar soft part sarcoma
  Bipolar disorder
  Bone osteosarcoma
  Breast cancer
  Breast carcinoma
  Carcinoma of esophagus
  Clear cell renal carcinoma
  Endometrial carcinoma
  Esophageal cancer
  Esophageal squamous cell carcinoma
  Glioblastoma multiforme
  Glioma
  High blood pressure
  Major depressive disorder
  Matthew-Wood syndrome
  Mood disorder
  Neoplasm
  Neoplasm of esophagus
  Nephropathy
  Osteoarthritis
  Osteosarcoma
  Prostate cancer
  Prostate carcinoma
  Renal cell carcinoma
  Rheumatoid arthritis
  Lung adenocarcinoma
  Triple negative breast cancer
  Advanced cancer
  Endometrial cancer
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid tumor
• UniProt ID: BHE41_HUMAN
• Pfam ID: PF07527 ; PF00010
• Sequence:
  MDEGIPHLQERQLLEHRDFIGLDYSSLYMCKPKRSMKRDDTKDTYKLPHRLIEKKRRDRI
  NECIAQLKDLLPEHLKLTTLGHLEKAVVLELTLKHLKALTALTEQQHQKIIALQNGERSL
  KSPIQSDLDAFHSGFQTCAKEVLQYLSRFESWTPREPRCVQLINHLHAVATQFLPTPQLL
  TQQVPLSKGTGAPSAAGSAAAPCLERAGQKLEPLAYCVPVIQRTQPSAELAAENDTDTDS
  GYGGEAEARPDREKGKGAGASRVTIKQEPPGEDSPAPKRMKLDSRGGGSGGGPGGGAAAA
  AAALLGPDPAAAAALLRPDAALLSSLVAFGGGGGAPFPQPAAAAAPFCLPFCFLSPSAAA
  AYVQPFLDKSGLEKYLYPAAAAAPFPLLYPGIPAPAAAAAAAAAAAAAAAAFPCLSSVLS
  PPPEKAGAAAATLLPHEVAPLGAPHPQHPHGRTHLPFAGPREPGNPESSAQEDPSQPGKE
  AP
• Function: Transcriptional repressor involved in the regulation of the circadian rhythm by negatively regulating the activity of the clock genes and clock-controlled genes. Acts as the negative limb of a novel autoregulatory feedback loop (DEC loop) which differs from the one formed by the PER and CRY transcriptional repressors (PER/CRY loop). Both these loops are interlocked as it represses the expression of PER1 and in turn is repressed by PER1/2 and CRY1/2. Represses the activity of the circadian transcriptional activator: CLOCK-BMAL1 heterodimer by competing for the binding to E-box elements (5'-CACGTG-3') found within the promoters of its target genes. Negatively regulates its own expression and the expression of DBP and BHLHE41/DEC2. Acts as a corepressor of RXR and the RXR-LXR heterodimers and represses the ligand-induced RXRA/B/G, NR1H3/LXRA, NR1H4 and VDR transactivation activity. Inhibits HNF1A-mediated transactivation of CYP1A2, CYP2E1 AND CYP3A11.
• Tissue Specificity: Highly expressed in skeletal muscle and brain, moderately expressed in pancreas and heart, weakly expressed in placenta, lung, liver and kidney.
• KEGG Pathway: Circadian rhythm (hsa04710)
• Reactome Pathway:
  Circadian Clock (R-HSA-400253)
  BMAL1 (R-HSA-1368108)

Molecular Interaction Atlas (MIA) of This DOT

38 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung cancer	DISCM4YA	Definitive	Biomarker	[1]
Lung carcinoma	DISTR26C	Definitive	Biomarker	[2]
Lung neoplasm	DISVARNB	Definitive	Biomarker	[1]
Pancreatic cancer	DISJC981	Definitive	Biomarker	[3]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[4]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[5]
Alveolar soft part sarcoma	DISLKJKZ	Strong	Genetic Variation	[6]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[7]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[8]
Breast cancer	DIS7DPX1	Strong	Biomarker	[9]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[9]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[10]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[11]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[12]
Esophageal cancer	DISGB2VN	Strong	Biomarker	[10]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[13]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[5]
Glioma	DIS5RPEH	Strong	Altered Expression	[5]
High blood pressure	DISY2OHH	Strong	Altered Expression	[14]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[15]
Matthew-Wood syndrome	DISA7HR7	Strong	Biomarker	[3]
Mood disorder	DISLVMWO	Strong	Genetic Variation	[15]
Neoplasm	DISZKGEW	Strong	Biomarker	[10]
Neoplasm of esophagus	DISOLKAQ	Strong	Biomarker	[10]
Nephropathy	DISXWP4P	Strong	Biomarker	[16]
Osteoarthritis	DIS05URM	Strong	Biomarker	[17]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[8]
Prostate cancer	DISF190Y	Strong	Biomarker	[18]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[18]
Renal cell carcinoma	DISQZ2X8	Strong	Genetic Variation	[19]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[17]
Lung adenocarcinoma	DISD51WR	moderate	Altered Expression	[2]
Triple negative breast cancer	DISAMG6N	moderate	Biomarker	[20]
Advanced cancer	DISAT1Z9	Limited	Genetic Variation	[11]
Endometrial cancer	DISW0LMR	Limited	Biomarker	[12]
Thyroid cancer	DIS3VLDH	Limited	Biomarker	[21]
Thyroid gland carcinoma	DISMNGZ0	Limited	Biomarker	[21]
Thyroid tumor	DISLVKMD	Limited	Biomarker	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Class E basic helix-loop-helix protein 41 (BHLHE41) affects the response to substance of Fluorouracil.	[36]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Class E basic helix-loop-helix protein 41 (BHLHE41).	[22]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Class E basic helix-loop-helix protein 41 (BHLHE41).	[23]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Class E basic helix-loop-helix protein 41 (BHLHE41).	[24]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Class E basic helix-loop-helix protein 41 (BHLHE41).	[25]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Class E basic helix-loop-helix protein 41 (BHLHE41).	[26]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Class E basic helix-loop-helix protein 41 (BHLHE41).	[27]
Marinol	DM70IK5	Approved	Marinol increases the expression of Class E basic helix-loop-helix protein 41 (BHLHE41).	[28]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Class E basic helix-loop-helix protein 41 (BHLHE41).	[29]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Class E basic helix-loop-helix protein 41 (BHLHE41).	[30]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Class E basic helix-loop-helix protein 41 (BHLHE41).	[31]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Class E basic helix-loop-helix protein 41 (BHLHE41).	[32]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Class E basic helix-loop-helix protein 41 (BHLHE41).	[34]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Class E basic helix-loop-helix protein 41 (BHLHE41).	[35]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Class E basic helix-loop-helix protein 41 (BHLHE41).	[33]

References

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• [17] Differentially Expressed in Chondrocytes 2 (DEC2) Increases the Expression of IL-1 and Is Abundantly Present in Synovial Membrane in Rheumatoid Arthritis.PLoS One. 2015 Dec 28;10(12):e0145279. doi: 10.1371/journal.pone.0145279. eCollection 2015.
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• [35] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
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