Details of the Drug

General Information of Drug (ID: DM0NZDT)

Drug Name

Pactimibe

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]

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 2

Molecular Weight (mw)

416.6

Topological Polar Surface Area (xlogp)

6.3

Rotatable Bond Count (rotbonds)

11

Hydrogen Bond Donor Count (hbonddonor)

2

Hydrogen Bond Acceptor Count (hbondacc)

4

Chemical Identifiers

Formula: C25H40N2O3
IUPAC Name: 2-[7-(2,2-dimethylpropanoylamino)-4,6-dimethyl-1-octyl-2,3-dihydroindol-5-yl]acetic acid
Canonical SMILES: CCCCCCCCN1CCC2=C(C(=C(C(=C21)NC(=O)C(C)(C)C)C)CC(=O)O)C
InChI: InChI=1S/C25H40N2O3/c1-7-8-9-10-11-12-14-27-15-13-19-17(2)20(16-21(28)29)18(3)22(23(19)27)26-24(30)25(4,5)6/h7-16H2,1-6H3,(H,26,30)(H,28,29)
InChIKey: TXIIZHHIOHVWJD-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 3081927
CAS Number: 189198-30-9
DrugBank ID: DB12971
TTD ID: D02GWF
INTEDE ID: DR1871

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]

------------------------------------------------------------------------------------

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease

Arteriosclerosis

ICD Disease Classification

BD40

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Liver carboxylesterase (CES1)	DTT	CES1	3.82E-08	1.86	1.9
Cytochrome P450 2D6 (CYP2D6)	DME	CYP2D6	5.05E-04	-1.51E-01	-8.87E-01

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

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	Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity in human liver microsomes. Cancer Chemother Pharmacol. 1993;32(6):491-5.
5	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.
6	CYP2D6 polymorphisms and tamoxifen metabolism: clinical relevance. Curr Oncol Rep. 2010 Jan;12(1):7-15.
7	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.
8	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.
9	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.
10	Effects of propofol on human hepatic microsomal cytochrome P450 activities. Xenobiotica. 1998 Sep;28(9):845-53.
11	Pharmacogenetics of schizophrenia. Am J Med Genet. 2000 Spring;97(1):98-106.
12	Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70.
13	Structure-activity relationship for human cytochrome P450 substrates and inhibitors. Drug Metab Rev. 2002 Feb-May;34(1-2):69-82.
14	How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
15	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.
16	Prospects for drug therapy for hyperlipoproteinaemia. Diabete Metab. 1995 Apr;21(2):139-46.
17	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).
18	New advances in lipid-modifying therapies for reducing cardiovascular risk. Cardiology. 2002;97(2):59-66.
19	Effect of the acyl-CoA:cholesterol acyltransferase inhibitor, E5324, on experimental atherosclerosis in rabbits. Atherosclerosis. 1994 Jun;107(2):187-201.
20	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.
21	Acyl-coenzyme A:cholesterol-acyltransferase (ACAT) inhibitors modulate monocyte adhesion to aortic endothelial cells. Atherosclerosis. 1995 Jan 6;112(1):7-17.
22	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.