Details of Drug Off-Target (DOT)

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

• DOT Name: Muscarinic acetylcholine receptor M5 (CHRM5)
• Gene Name: CHRM5
• UniProt ID: ACM5_HUMAN
• PDB ID: 6OL9
• Pfam ID: PF00001
• Sequence:
  MEGDSYHNATTVNGTPVNHQPLERHRLWEVITIAAVTAVVSLITIVGNVLVMISFKVNSQ
  LKTVNNYYLLSLACADLIIGIFSMNLYTTYILMGRWALGSLACDLWLALDYVASNASVMN
  LLVISFDRYFSITRPLTYRAKRTPKRAGIMIGLAWLISFILWAPAILCWQYLVGKRTVPL
  DECQIQFLSEPTITFGTAIAAFYIPVSVMTILYCRIYRETEKRTKDLADLQGSDSVTKAE
  KRKPAHRALFRSCLRCPRPTLAQRERNQASWSSSRRSTSTTGKPSQATGPSANWAKAEQL
  TTCSSYPSSEDEDKPATDPVLQVVYKSQGKESPGEEFSAEETEETFVKAETEKSDYDTPN
  YLLSPAAAHRPKSQKCVAYKFRLVVKADGNQETNNGCHKVKIMPCPFPVAKEPSTKGLNP
  NPSHQMTKRKRVVLVKERKAAQTLSAILLAFIITWTPYNIMVLVSTFCDKCVPVTLWHLG
  YWLCYVNSTVNPICYALCNRTFRKTFKMLLLCRWKKKKVEEKLYWQGNSKLP
• Function: The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.
• KEGG Pathway:
  Calcium sig.ling pathway (hsa04020)
  Neuroactive ligand-receptor interaction (hsa04080)
  Cholinergic sy.pse (hsa04725)
  Regulation of actin cytoskeleton (hsa04810)
  Alzheimer disease (hsa05010)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
• Reactome Pathway:
  G alpha (q) signalling events (R-HSA-416476)
  Muscarinic acetylcholine receptors (R-HSA-390648)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methylscopolamine	DM5VWOB	Approved	Muscarinic acetylcholine receptor M5 (CHRM5) affects the binding of Methylscopolamine.	[7]
Gallamine Triethiodide	DMPO0MS	Approved	Muscarinic acetylcholine receptor M5 (CHRM5) affects the binding of Gallamine Triethiodide.	[7]
[3H]dimethyl-W84	DMBWAIE	Investigative	Muscarinic acetylcholine receptor M5 (CHRM5) affects the binding of [3H]dimethyl-W84.	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Muscarinic acetylcholine receptor M5 (CHRM5).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Muscarinic acetylcholine receptor M5 (CHRM5).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Muscarinic acetylcholine receptor M5 (CHRM5).	[2]
Acetylcholine	DMDF79Z	Approved	Acetylcholine increases the activity of Muscarinic acetylcholine receptor M5 (CHRM5).	[3]

2 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
	DM1FBZ7		affects the binding of Muscarinic acetylcholine receptor M5 (CHRM5).	[5]
[3H]QNB	DMC1WHR	Investigative	[3H]QNB affects the binding of Muscarinic acetylcholine receptor M5 (CHRM5).	[6]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [3] Characterizing fucoxanthin as a selective dopamine D(3)/D(4) receptor agonist: Relevance to Parkinson's disease. Chem Biol Interact. 2019 Sep 1;310:108757. doi: 10.1016/j.cbi.2019.108757. Epub 2019 Jul 16.
• [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] Inhalation by design: novel tertiary amine muscarinic M? receptor antagonists with slow off-rate binding kinetics for inhaled once-daily treatment of chronic obstructive pulmonary disease. J Med Chem. 2011 Oct 13;54(19):6888-904. doi: 10.1021/jm200884j. Epub 2011 Sep 20.
• [6] A snake venom inhibitor to muscarinic acetylcholine receptor (mAChR): isolation and interaction with cloned human mAChR. Arch Biochem Biophys. 2000 May 15;377(2):290-5. doi: 10.1006/abbi.2000.1784.
• [7] Allosteric interactions with muscarinic acetylcholine receptors: complex role of the conserved tryptophan M2422Trp in a critical cluster of amino acids for baseline affinity, subtype selectivity, and cooperativity. Mol Pharmacol. 2006 Jul;70(1):181-93. doi: 10.1124/mol.106.023481. Epub 2006 Apr 26.