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

General Information of Drug (ID: DMWTPCA)

• Drug Name: L-651582 Drug Info
• Synonyms: Carboxyamidotriazole (CAI)

Indication

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Phase 3	[1]

• Cross-matching ID:
  PubChem CID: 108144
  CAS Number: CAS 99519-84-3
  TTD Drug ID: DMWTPCA
  INTEDE Drug ID: DR0273

Molecule-Related Drug Atlas

Drug(s) Targeting Muscarinic acetylcholine receptor M5 (CHRM5)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Promazine	DMZAL7W	Acute intermittent hepatic porphyria	5C58.11	Approved	[3]
ACECLIDINE	DMOLNCZ	Glaucoma/ocular hypertension	9C61	Approved	[4]
Pilocarpine	DMV9ADG	Glaucoma/ocular hypertension	9C61	Approved	[5]
Anisodine	DMNOSWU	Central and peripheral nervous disease	8A04-8E7Z	Approved	[6]
Atropine	DMEN6X7	Organophosphate poisoning	NE6Z	Approved	[7]
Propiverine	DMUWBIJ	Urinary incontinence	MF50.2	Approved	[8]
Umeclidinium	DM4E8O9	Chronic obstructive pulmonary disease	CA22	Approved	[9]
Cimetropium bromide	DMZHPNE	Gastric motility disorder	DA21	Approved	[10]
Butylscopolamine	DMZKXB7	Dysmenorrhea	GA34.3	Approved	[11]
Trospium	DMX6RTG	Overactive bladder	GC50.0	Approved	[12]

Drug(s) Metabolized By Cytochrome P450 3A4 (CYP3A4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[13]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[14]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[15]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[16]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[17]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[18]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[19]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[20]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[14]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[21]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Muscarinic acetylcholine receptor M5 (CHRM5)	TTH18TF	ACM5_HUMAN	Modulator	[1]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[2]

References

• [1] The antiproliferative and antimetastatic compound L651582 inhibits muscarinic acetylcholine receptor-stimulated calcium influx and arachidonic acid release. J Pharmacol Exp Ther. 1991 Jun;257(3):967-71.
• [2] Integrated analysis on the physicochemical properties of dihydropyridine calcium channel blockers in grapefruit juice interactions. Curr Pharm Biotechnol. 2012 Jul;13(9):1705-17.
• [3] Muscarinic cholinergic and histamine H1 receptor binding of phenothiazine drug metabolites. Life Sci. 1988;43(5):405-12.
• [4] Design, synthesis, and neurochemical evaluation of 5-(3-alkyl-1,2,4- oxadiazol-5-yl)-1,4,5,6-tetrahydropyrimidines as M1 muscarinic receptor agonists. J Med Chem. 1993 Apr 2;36(7):842-7.
• [5] Retinoic acid prevents virus-induced airway hyperreactivity and M2 receptor dysfunction via anti-inflammatory and antiviral effects. Am J Physiol Lung Cell Mol Physiol. 2009 Aug;297(2):L340-6.
• [6] Medicinal plants in therapy. Bull World Health Organ. 1985;63(6):965-81.
• [7] Additive protective effects of donepezil and nicotine against salsolinol-induced cytotoxicity in SH-SY5Y cells. Neurotox Res. 2009 Oct;16(3):194-204.
• [8] Affinity profiles of various muscarinic antagonists for cloned human muscarinic acetylcholine receptor (mAChR) subtypes and mAChRs in rat heart and submandibular gland. Life Sci. 1999;64(25):2351-8.
• [9] 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: 7354).
• [10] Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
• [11] Comparison of pharmacological effects of L- and DL-n-butyl-scopolamine in rat uterus. Yao Xue Xue Bao. 1994;29(1):24-7.
• [12] Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34.
• [13] Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
• [14] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [15] Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
• [16] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [17] Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
• [18] Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
• [19] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [20] The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
• [21] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.