Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMXJASC)

• Drug Name: ML375 Drug Info
• Synonyms: VU0483253-3

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 71598521
  TTD Drug ID: DMXJASC

Molecule-Related Drug Atlas

Drug(s) Targeting Muscarinic acetylcholine receptor (CHRM)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Acetylcholine	DMDF79Z	Cataract	9B10	Approved	[3]
Tiotropium	DMFDC0Q	Chronic obstructive pulmonary disease	CA22	Approved	[4]
Darifenacin	DMWXLYZ	Overactive bladder	GC50.0	Approved	[5]
Methylscopolamine	DM5VWOB	Peptic ulcer	DA61	Approved	[6]
Clidinium	DMUMQZ0	Abdominal stomach pain	DD91.4	Approved	[7]
Oxybutynin hydrochloride	DMF2KLU	Urinary incontinence	MF50.2	Approved	[8]
Incruse Ellipta	DM32GSJ	Chronic obstructive pulmonary disease	CA22	Approved	[9]
Revefenacin	DMMP5SI	Chronic obstructive pulmonary disease	CA22	Approved	[10]
Scopolamine	DMOM8AL	Addictive disorder	6C50-6C5Z	Approved	[11]
Isopropamide iodide	DMQYV60	Allergic rhinitis	CA08.0	Approved	[12]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Muscarinic acetylcholine receptor (CHRM)	TTOXS3C	NOUNIPROTAC	Modulator (allosteric modulator)	[2]

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7631).
• [2] Discovery of the first M5-selective and CNS penetrant negative allosteric modulator (NAM) of a muscarinic acetylcholine receptor: (S)-9b-(4-chlorophenyl)-1-(3,4-difluorobenzoyl)-2,3-dihydro-1H-imidazo[2,1-a]isoindol-5(9bH)-one (ML375). J Med Chem. 2013 Nov 27;56(22):9351-5.
• [3] Thiochrome enhances acetylcholine affinity at muscarinic M4 receptors: receptor subtype selectivity via cooperativity rather than affinity. Mol Pharmacol. 2004 Jan;65(1):257-66.
• [4] Pharmacological characterization of GSK573719 (umeclidinium): a novel, long-acting, inhaled antagonist of the muscarinic cholinergic receptors for treatment of pulmonary diseases. J Pharmacol Exp Ther. 2013 May;345(2):260-70.
• [5] Characterisation of [3H]-darifenacin as a novel radioligand for the study of muscarinic M3 receptors. J Recept Signal Transduct Res. 1997 Jan-May;17(1-3):177-84.
• [6] Lithocholylcholine, a bile acid/acetylcholine hybrid, is a muscarinic receptor antagonist. J Pharmacol Exp Ther. 2002 Oct;303(1):29-35.
• [7] Pharmacological comparison of the cloned human and rat M2 muscarinic receptor genes expressed in the murine fibroblast (B82) cell line. J Pharmacol Exp Ther. 1998 Feb;284(2):500-7.
• [8] Effects of propiverine hydrochloride (propiverine) on the muscarinic receptor binding affinity in guinea pig tissues and on salivation in conscious dogs. Nihon Yakurigaku Zasshi. 1999 Mar;113(3):157-66.
• [9] Clinical pipeline report, company report or official report of GlaxoSmithKline.
• [10] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [11] The amygdala modulates morphine-induced state-dependent memory retrieval via muscarinic acetylcholine receptors. Neuroscience. 2009 May 5;160(2):255-63.
• [12] Competitive and non-competitive antagonism exhibited by 'selective' antagonists at atrial and ileal muscarinic receptor subtypes. Br J Pharmacol. 1987 Apr;90(4):701-7.