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

General Information of Drug (ID: DM0NZDT)

• Drug Name: PACTIMIBE Drug Info
• Synonyms: Pactimibe; 189198-30-9; UNII-D874R9PZ9T; D874R9PZ9T; CHEMBL478858; Pactimibe [INN:BAN]; [7-(2,2-Dimethylpropanamido)-4,6-dimethyl-1-octylindolin-5-yl]acetic acid; (7-(2,2-Dimethylpropanamido)-4,6-dimethyl-1-octylindolin-5-yl)acetic acid; AC1MIXTD; SCHEMBL282098; CTK0H7032; DTXSID80172315; TXIIZHHIOHVWJD-UHFFFAOYSA-N; ZINC1545445; BDBM50263192; DB12971; 2-[7-(2,2-Dimethylpropanoylamino)-4,6-dimethyl-1-octyl-2,3-dihydroindo L-5-yl]acetic acid; AN-30445; 198P309

Indication

Disease Entry	ICD 11	Status	REF
Arteriosclerosis	BD40	Phase 2/3	[1]

• Cross-matching ID:
  PubChem CID: 3081927
  CAS Number: CAS 189198-30-9
  TTD Drug ID: DM0NZDT
  INTEDE Drug ID: DR1871

Molecule-Related Drug Atlas

Drug(s) Targeting Liver carboxylesterase (CES1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cholic Acid	DM7OKQV	Cholelithiasis	DC11	Approved	[4]
K-604	DMQVN6P	Arteriosclerosis	BD40	Phase 2	[5]
Eldacimibe	DML7WP0	Hyperlipidaemia	5C80	Phase 2	[6]
GR148672X	DM7W6YN	Acute lymphoblastic leukaemia	2A85	Clinical trial	[7]
Avasimibe	DMFG4OM	Peripheral vascular disease	BD4Z	Discontinued in Phase 3	[8]
E-5324	DM562BM	Hyperlipidaemia	5C80	Discontinued in Phase 2	[9]
RP-64477	DMTQ3BS	Hyperlipidaemia	5C80	Discontinued in Phase 2	[10]
CI-976	DMBO28J	Hyperlipidaemia	5C80	Discontinued in Phase 2	[11]
CL-283796	DM7LIDT	Hyperlipidaemia	5C80	Discontinued in Phase 2	[12]
Eflucimibe	DMZXRF2	Hyperlipidaemia	5C80	Discontinued in Phase 2	[6]

Drug(s) Metabolized By Cytochrome P450 2D6 (CYP2D6)

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]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[16]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[17]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[18]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[19]
Dopamine	DMPGUCF	Acromegaly	5A60.0	Approved	[20]
Nicotine	DMWX5CO	Lung cancer	2C25.0	Approved	[21]
Propranolol	DM79NTF	Angina pectoris	BA40	Approved	[22]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Liver carboxylesterase (CES1)	TTMF541	EST1_HUMAN	Inhibitor	[2]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2D6 (CYP2D6) Main DME	DECB0K3	CP2D6_HUMAN	Substrate	[3]

References

• [1] ClinicalTrials.gov (NCT00151788) Efficacy and Safety of the ACAT Inhibitor CS-505 (Pactimibe) for Reducing the Progression of Carotid Artery Disease. This Study is Also Known as CAPTIVATE.. U.S. National Institutes of Health.
• [2] Novel indoline-based acyl-CoA:cholesterol acyltransferase inhibitor with antiperoxidative activity: improvement of physicochemical properties and b... J Med Chem. 2008 Aug 14;51(15):4823-33.
• [3] Novel binding mode of the acidic CYP2D6 substrates pactimibe and its metabolite R-125528. Drug Metab Dispos. 2008 Sep;36(9):1938-43.
• [4] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [5] A selective ACAT-1 inhibitor, K-604, suppresses fatty streak lesions in fat-fed hamsters without affecting plasma cholesterol levels. Atherosclerosis. 2007 Apr;191(2):290-7.
• [6] Prospects for drug therapy for hyperlipoproteinaemia. Diabete Metab. 1995 Apr;21(2):139-46.
• [7] 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. (Target id: 2592).
• [8] New advances in lipid-modifying therapies for reducing cardiovascular risk. Cardiology. 2002;97(2):59-66.
• [9] Effect of the acyl-CoA:cholesterol acyltransferase inhibitor, E5324, on experimental atherosclerosis in rabbits. Atherosclerosis. 1994 Jun;107(2):187-201.
• [10] RP 64477: a potent inhibitor of acyl-coenzyme A:cholesterol O-acyltransferase with low systemic bioavailability. Biochem Pharmacol. 1996 Feb 23;51(4):413-21.
• [11] Acyl-coenzyme A:cholesterol-acyltransferase (ACAT) inhibitors modulate monocyte adhesion to aortic endothelial cells. Atherosclerosis. 1995 Jan 6;112(1):7-17.
• [12] ACAT inhibitors CL 283,546 and CL 283,796 reduce LDL cholesterol without affecting cholesterol absorption in African green monkeys. J Lipid Res. 1995 Jun;36(6):1199-210.
• [13] Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity in human liver microsomes. Cancer Chemother Pharmacol. 1993;32(6):491-5.
• [14] Effect of genetic polymorphism on the metabolism of endogenous neuroactive substances, progesterone and p-tyramine, catalyzed by CYP2D6. Brain Res Mol Brain Res. 2004 Oct 22;129(1-2):117-23.
• [15] CYP2D6 polymorphisms and tamoxifen metabolism: clinical relevance. Curr Oncol Rep. 2010 Jan;12(1):7-15.
• [16] 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.
• [17] 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.
• [18] Inhibition of cytochrome P450 2D6: structure-activity studies using a series of quinidine and quinine analogues. Chem Res Toxicol. 2003 Apr;16(4):450-9.
• [19] Effects of propofol on human hepatic microsomal cytochrome P450 activities. Xenobiotica. 1998 Sep;28(9):845-53.
• [20] Pharmacogenetics of schizophrenia. Am J Med Genet. 2000 Spring;97(1):98-106.
• [21] Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70.
• [22] Structure-activity relationship for human cytochrome P450 substrates and inhibitors. Drug Metab Rev. 2002 Feb-May;34(1-2):69-82.