Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6V19Y9)

• DOT Name: Adrenocorticotropic hormone receptor (MC2R)
• Synonyms: ACTH receptor; ACTH-R; Adrenocorticotropin receptor; Melanocortin receptor 2; MC2-R
• Gene Name: MC2R
• Related Disease:
  Glucocorticoid deficiency 1
  Familial glucocorticoid deficiency
• UniProt ID: ACTHR_HUMAN
• PDB ID: 8GY7
• Pfam ID: PF00001
• Sequence:
  MKHIINSYENINNTARNNSDCPRVVLPEEIFFTISIVGVLENLIVLLAVFKNKNLQAPMY
  FFICSLAISDMLGSLYKILENILIILRNMGYLKPRGSFETTADDIIDSLFVLSLLGSIFS
  LSVIAADRYITIFHALRYHSIVTMRRTVVVLTVIWTFCTGTGITMVIFSHHVPTVITFTS
  LFPLMLVFILCLYVHMFLLARSHTRKISTLPRANMKGAITLTILLGVFIFCWAPFVLHVL
  LMTFCPSNPYCACYMSLFQVNGMLIMCNAVIDPFIYAFRSPELRDAFKKMIFCSRYW
• Function: Receptor for corticotropin (ACTH). This receptor is mediated by G proteins (G(s)) which activate adenylate cyclase (cAMP).
• Tissue Specificity: Melanocytes and corticoadrenal tissue.
• KEGG Pathway:
  cAMP sig.ling pathway (hsa04024)
  Neuroactive ligand-receptor interaction (hsa04080)
  Aldosterone synthesis and secretion (hsa04925)
  Cortisol synthesis and secretion (hsa04927)
  Cushing syndrome (hsa04934)
• Reactome Pathway:
  G alpha (s) signalling events (R-HSA-418555)
  Defective ACTH causes obesity and POMCD (R-HSA-5579031)
  Peptide ligand-binding receptors (R-HSA-375276)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Glucocorticoid deficiency 1	DISCTX0T	Definitive	Autosomal recessive	[1]
Familial glucocorticoid deficiency	DISG7TB4	Supportive	Autosomal recessive	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Lamotrigine	DM8SXYG	Approved	Adrenocorticotropic hormone receptor (MC2R) increases the response to substance of Lamotrigine.	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Adrenocorticotropic hormone receptor (MC2R).	[3]
Forskolin	DM6ITNG	Investigative	Forskolin increases the expression of Adrenocorticotropic hormone receptor (MC2R).	[6]

2 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 Adrenocorticotropic hormone receptor (MC2R).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Adrenocorticotropic hormone receptor (MC2R).	[5]

References

• [1] Familial glucocorticoid deficiency associated with point mutation in the adrenocorticotropin receptor. Lancet. 1993 Feb 20;341(8843):461-2. doi: 10.1016/0140-6736(93)90208-x.
• [2] Mutations of the ACTH receptor gene are only one cause of familial glucocorticoid deficiency. Hum Mol Genet. 1994 Apr;3(4):585-8. doi: 10.1093/hmg/3.4.585.
• [3] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [4] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [5] 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.
• [6] The effect of valproate and levetiracetam on steroidogenesis in forskolin-stimulated H295R cells. Epilepsia. 2010 Nov;51(11):2280-8.
• [7] Genetic association study of treatment response with olanzapine/fluoxetine combination or lamotrigine in bipolar I depression. J Clin Psychiatry. 2010 May;71(5):599-605. doi: 10.4088/JCP.08m04632gre. Epub 2009 Dec 15.