General Information of Drug Off-Target (DOT) (ID: OT2MOC4T)

DOT Name Corticoliberin (CRH)
Synonyms Corticotropin-releasing factor; CRF; Corticotropin-releasing hormone
Gene Name CRH
Related Disease
Autosomal dominant nocturnal frontal lobe epilepsy ( )
Frontal lobe epilepsy ( )
Epilepsy ( )
UniProt ID
CRF_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1GO9; 1GOE; 3EHT; 3EHU; 6P9X
Pfam ID
PF00473
Sequence
MRLPLLVSAGVLLVALLPCPPCRALLSRGPVPGARQAPQHPQPLDFFQPPPQSEQPQQPQ
ARPVLLRMGEEYFLRLGNLNKSPAAPLSPASSLLAGGSGSRPSPEQATANFFRVLLQQLL
LPRRSLDSPAALAERGARNALGGHQEAPERERRSEEPPISLDLTFHLLREVLEMARAEQL
AQQAHSNRKLMEIIGK
Function Hormone regulating the release of corticotropin from pituitary gland. Induces NLRP6 in intestinal epithelial cells, hence may influence gut microbiota profile.
Tissue Specificity Produced by the hypothalamus and placenta.
KEGG Pathway
cAMP sig.ling pathway (hsa04024 )
Neuroactive ligand-receptor interaction (hsa04080 )
Long-term depression (hsa04730 )
Cushing syndrome (hsa04934 )
Alcoholism (hsa05034 )
Reactome Pathway
G alpha (s) signalling events (R-HSA-418555 )
MECP2 regulates transcription of neuronal ligands (R-HSA-9022702 )
Class B/2 (Secretin family receptors) (R-HSA-373080 )

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Autosomal dominant nocturnal frontal lobe epilepsy DISE3C4O Supportive Autosomal dominant [1]
Frontal lobe epilepsy DISHN8AO Limited Autosomal dominant [2]
Epilepsy DISBB28L Refuted Autosomal dominant [3]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Regulation of Drug Effects of 2 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Progesterone DMUY35B Approved Corticoliberin (CRH) decreases the abundance of Progesterone. [16]
Hydrocortisone DMGEMB7 Approved Corticoliberin (CRH) increases the abundance of Hydrocortisone. [17]
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15 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the expression of Corticoliberin (CRH). [4]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Corticoliberin (CRH). [5]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of Corticoliberin (CRH). [6]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide decreases the expression of Corticoliberin (CRH). [7]
Clozapine DMFC71L Approved Clozapine decreases the expression of Corticoliberin (CRH). [8]
Pioglitazone DMKJ485 Approved Pioglitazone increases the expression of Corticoliberin (CRH). [9]
Haloperidol DM96SE0 Approved Haloperidol decreases the expression of Corticoliberin (CRH). [8]
Thioridazine DM35M8J Approved Thioridazine decreases the expression of Corticoliberin (CRH). [8]
Risperidone DMN6DXL Approved Risperidone decreases the expression of Corticoliberin (CRH). [8]
Terbutaline DMD4381 Approved Terbutaline decreases the expression of Corticoliberin (CRH). [10]
Tetrodotoxin DMWMPRG Approved Tetrodotoxin decreases the activity of Corticoliberin (CRH). [11]
Promazine DMZAL7W Approved Promazine decreases the expression of Corticoliberin (CRH). [8]
Meglitinides DM1OFHN Approved Meglitinides decreases the expression of Corticoliberin (CRH). [8]
Chlorpromazine DMBGZI3 Phase 3 Trial Chlorpromazine decreases the expression of Corticoliberin (CRH). [8]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Corticoliberin (CRH). [12]
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⏷ Show the Full List of 15 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the methylation of Corticoliberin (CRH). [13]
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2 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT
Drug Name Drug ID Highest Status Interaction REF
Forskolin DM6ITNG Investigative Forskolin increases the secretion of Corticoliberin (CRH). [14]
Protoporphyrin IX DMWYE7A Investigative Protoporphyrin IX increases the secretion of Corticoliberin (CRH). [15]
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References

1 Frontal lobe epilepsy and mutations of the corticotropin-releasing hormone gene. Ann Neurol. 2005 Dec;58(6):899-904. doi: 10.1002/ana.20660.
2 Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
3 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
4 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
5 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
6 Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
7 Oxidative Stress Alters miRNA and Gene Expression Profiles in Villous First Trimester Trophoblasts. Biomed Res Int. 2015;2015:257090. doi: 10.1155/2015/257090. Epub 2015 Aug 3.
8 Antipsychotic drugs inhibit the human corticotropin-releasing-hormone gene promoter activity in neuro-2A cells-an involvement of protein kinases. Neuropsychopharmacology. 2006 Apr;31(4):853-65. doi: 10.1038/sj.npp.1300911.
9 Peroxisome proliferator activated receptor gamma (PPAR-gama) ligand pioglitazone regulated gene networks in term human primary trophoblast cells. Reprod Toxicol. 2018 Oct;81:99-107.
10 Terbutaline inhibits corticotropin-releasing hormone (CRH) expression in human trophoblast cells. J Matern Fetal Neonatal Med. 2006 Nov;19(11):735-9. doi: 10.1080/14767050600886724.
11 Actions of endothelin and corticotropin releasing factor in the guinea-pig ileum: no evidence for an interaction with capsaicin-sensitive neurons. Neuropeptides. 2003 Aug;37(4):220-32. doi: 10.1016/s0143-4179(03)00048-9.
12 Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
13 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
14 Exposure to perfluorobutane sulfonate and perfluorooctanesulfonic acid disrupts the production of angiogenesis factors and stress responses in human placental syncytiotrophoblast. Reprod Toxicol. 2020 Dec;98:269-277. doi: 10.1016/j.reprotox.2020.10.013. Epub 2020 Nov 2.
15 Evidence for a functional link between the heme oxygenase-carbon monoxide pathway and corticotropin-releasing hormone release from primary cultures of human trophoblast cells. J Clin Endocrinol Metab. 2001 Jan;86(1):317-23. doi: 10.1210/jcem.86.1.7091.
16 Corticotropin-releasing hormone inhibits progesterone production in cultured human placental trophoblasts. J Mol Endocrinol. 2006 Dec;37(3):533-40.
17 Influence of cocaine dependence and early life stress on pituitary-adrenal axis responses to CRH and the Trier social stressor. Psychoneuroendocrinology. 2010 Nov;35(10):1492-500. doi: 10.1016/j.psyneuen.2010.05.001. Epub 2010 May 31.