Drug Details

General Information of the Drug (ID: DR3599)
Name
Atorvastatin
Synonyms
atorvastatin; 134523-00-5; Cardyl; Lipitor; ATORVASTATIN CALCIUM; Torvast; (3R,5R)-7-(2-(4-Fluorophenyl)-5-isopropyl-3-phenyl-4-(phenylcarbamoyl)-1H-pyrrol-1-yl)-3,5-dihydroxyheptanoic acid; UNII-A0JWA85V8F; 110862-48-1; CI 981; Lipitor (TN); Tozalip; Xavator; A0JWA85V8F; CHEMBL1487; (R-(R*,R*))-2-(4-Fluorophenyl)-beta,delta-dihydroxy-5-(1-methylethyl)-3-phenyl-4-((phenylamino)carbonyl)-1H-pyrrole-1-heptanoic acid; CHEBI:39548; 134523-00-5 (free acid); (3R,5R)-7-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-(propan-2-yl)-1H-pyrrol-1-yl]-3,5-dihydroxyheptanoic acid; 134523-03-8; Atorvastatin [INN:BAN]; (3R,5R)-7-[2-(4-Fluorophenyl)-5-isopropyl-3-phenyl-4-phenylcarbamoylpyrrol-1-yl]-3,5-dihydroxyheptanoic acid; 1H-Pyrrole-1-heptanoic acid, 2-(4-fluorophenyl)-beta,delta-dihydroxy-5-(1-methylethyl)-3-phenyl-4-((phenylamino)carbonyl)-, (R-(R*,R*))-; Atorvastatin calcium salt; atorvastatina; atorvastatine; atrovastin; Atofast; Atorcor; Atorlip; Lipilou; Lipinon; Atorin; Ator; Lipitor(TM); (3R,5R)-7-[2-(4-fluorophenyl)-5-(1-methylethyl)-3-phenyl-4-(phenylcarbamoyl)-1H-pyrrol-1-yl]-3,5-dihydroxyheptanoic acid; (3R,5R)-7-[2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-(phenylcarbamoyl)pyrrol-1-yl]-3,5-dihydroxy-heptanoic acid; (3R,5R)-7-[3-(anilinocarbonyl)-5-(4-fluorophenyl)-2-isopropyl-4-phenyl-1H-pyrrol-1-yl]-3,5-dihydroxyheptanoic acid; Atorvastatin (INN); Sortis (TN); CCRIS 7159; MFCD00899261; C33H35FN2O5; HSDB 7039; NCGC00159458-03; atorvastatinum; rel-Atorvastatin; (betaR,deltaR)-2-(p-Fluorophenyl)-beta,delta-dihydroxy-5-isopropyl-3-phenyl-4-(phenylcarbamoyl)pyrrole-1-heptanoic acid; Atorvastatin & Primycin; DSSTox_CID_9868; SCHEMBL3831; DSSTox_RID_78825; DSSTox_GSID_29868; BIDD:GT0336; Atorvastatin (Relative Stereo); GTPL2949; DTXSID8029868; BDBM22164; DTXSID60274003; HMS3715L05; HMS3886C20; Lipilou; Tozalip; Torvast; Cardyl; ACT03225; HY-B0589; ZINC3920719; Tox21_302417; s5715; AKOS000281127; AC-9386; CCG-221172; DB01076; MCULE-2368532812; MRF-0000761; NCGC00159458-02; NCGC00159458-20; NCGC00255181-01; 1H-Pyrrole-1-heptanoic acid, 2-(4-fluorophenyl)-beta,delta-dihydroxy-5-(1-methylethyl)-3-phenyl-4-((phenylamino)carbonyl)-, (betaR,deltaR)-; 7-[2-(4-FLUORO-PHENYL)-5-ISOPROPYL-3-PHENYL-4-PHENYLCARBAMOYL-PYRROL-1-YL]- 3,5-DIHYDROXY-HEPTANOIC ACID; 7-[2-(4-FLUORO-PHENYL)-5-ISOPROPYL-3-PHENYL-4-PHENYLCARBAMOYL-PYRROL-1-YL]-3,5-DIHYDROXY-HEPTANOIC ACID; AS-35260; H942; CAS-134523-00-5; C06834; D07474; S-2492; Y-8867; 28052-EP2269989A1; 28052-EP2269990A1; 28052-EP2270011A1; 28052-EP2270505A1; 28052-EP2272825A2; 28052-EP2272841A1; 28052-EP2280001A1; 28052-EP2284158A1; 28052-EP2287165A2; 28052-EP2287166A2; 28052-EP2292600A1; 28052-EP2292620A2; 28052-EP2295406A1; 28052-EP2295409A1; 28052-EP2295417A1; 28052-EP2295422A2; 28052-EP2298731A1; 28052-EP2298742A1; 28052-EP2298745A1; 28052-EP2298769A1; 28052-EP2298772A1; 28052-EP2298776A1; 28052-EP2298779A1; 28052-EP2301923A1; 28052-EP2301931A1; 28052-EP2301936A1; 28052-EP2308839A1; 28052-EP2308878A2; 28052-EP2314588A1; 523A005; Q668093; SR-01000872702; SR-01000872702-1; BRD-K69726342-001-02-6; UNII-36TN91XZ0V component XUKUURHRXDUEBC-KAYWLYCHSA-N; (3R,5R)-7-[2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-phenylcarbamoyl-pyrrol-1-yl]-3,5-dihydroxy-heptanoic acid; (3R,5R)-7-[3-(anilinocarbonyl)-5-(4-fluorophenyl)-4-phenyl-2-(propan-2-yl)-1H-pyrrol-1-yl]-3,5-dihydroxyheptanoic acid; 1H-Pyrrole-1-heptanoic acid, 2-(4-fluorophenyl)-beta,delta-dihydroxy-5-(1-methylethyl)-3-phenyl-4-((phenylamino)carbonyl)-, (beta-R,delta-R)-;
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Molecular Type
Small molecule
Disease Cardiovascular disease [ICD-11: BA00-BE2Z] Approved [1]
Structure
Click to Download Mol
2D MOL

3D MOL

ADMET Property
Absorption AUC
The area under the plot of plasma concentration (AUC) of drug is 200 mcgh/L
Absorption Cmax
The maximum plasma concentration (Cmax) of drug is 28 mcg/L
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability
Bioavailability
The bioavailability of drug is 14%
Clearance
The total plasma clearance of drug is 625 mL/min
Elimination
Atorvastatin and its metabolites are mainly eliminated in the bile without enterohepatic recirculation
Elimination
1% of drug is excreted from urine in the unchanged form
Half-life
The concentration or amount of drug in body reduced by one-half in 14 hours (atorvastatin), and 30 hours (its metabolites)
Metabolism
The drug is metabolized via the cytochrome P450 3A4 in the intestine and liver
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 2.04573 micromolar/kg/day
Vd
The volume of distribution (Vd) of drug is 380 L
Water Solubility
The ability of drug to dissolve in water is measured as 0.0204 mg/mL
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    Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product
Formula
C33H35FN2O5
PubChem CID
60823
Canonical SMILES
CC(C)C1=C(C(=C(N1CCC(CC(CC(=O)O)O)O)C2=CC=C(C=C2)F)C3=CC=CC=C3)C(=O)NC4=CC=CC=C4
InChI
1S/C33H35FN2O5/c1-21(2)31-30(33(41)35-25-11-7-4-8-12-25)29(22-9-5-3-6-10-22)32(23-13-15-24(34)16-14-23)36(31)18-17-26(37)19-27(38)20-28(39)40/h3-16,21,26-27,37-38H,17-20H2,1-2H3,(H,35,41)(H,39,40)/t26-,27-/m1/s1
InChIKey
XUKUURHRXDUEBC-KAYWLYCHSA-N
CAS Number
CAS 134523-00-5
ChEBI ID
CHEBI:39548
TTD Drug ID
D01QIN
DrugBank ID
DB01076
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Natural Product(s) Able to Enhance the Efficacy of This Drug
          Ferulic acid      Ferula sinkiangensisK     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression IL6  Molecule Info 
Pathway MAP
Down-regulation Expression TNF  Molecule Info 
Pathway MAP
                    In-vivo Model Male Swiss albino mice were given a diet containing high fat.
                    Experimental
                    Result(s)		 Simultaneous treatment with AS, F and their combination protected against HFD induced weight gain and oxidative stress.
          Gamma tocotrienol      Bixa orellana     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
                    Biological
                    Regulation		 Induction Cell cycle arrest in G0/G1 phase
Increase DNA fragmentation
                    In-vitro Model HT29 CVCL_A8EZ Colorectal adenocarcinoma Mus musculus
HCT 116 CVCL_0291 Colon carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Atorvastatin with gamma-tocotrienol and celecoxib exhibited a strong synergy against human colon cancer cells in causing cell cycle arrest and apoptosis.
          Metformin      Galega officinalis     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [5]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vivo Model Clinical trial
                    Experimental
                    Result(s)		 Use of statin and metformin provides a synergistic improvement in gastrointestinal malignancies outcomes.
          Phloretin      Prunus armeniaca     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [6]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression CCNB1  Molecule Info 
Pathway MAP
Up-regulation Expression MYT1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation POLD1  Molecule Info 
Pathway MAP
                    In-vitro Model SW620 CVCL_0547 Colon adenocarcinoma Homo sapiens
HCT 116 CVCL_0291 Colon carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Phloretin and Atorvastatin produce a powerful synergistic interaction in suppressing colon cancer cell growth. This process was accomplished via the synergistic induction of apoptosis and the arrest of the cell cycle at the G2/M checkpoint, which resulted from downregulated cdc2 activation following combined treatment.
          Tanshinone IIA      Salvia miltiorrhiza     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [7]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vivo Model Six-week old male ApoE KO mice were used in this study.
                    Experimental
                    Result(s)		 Tan in conjunction with Ato represents an effective combination therapy to comprehensively combat atherogenesis in ApoE / mice by reducing plaque size and stabilizing vulnerable atheromatous plaques.
          Tocotrienols      Trachycarpus fortunei     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [8]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model HT29 CVCL_A8EZ Colorectal adenocarcinoma Mus musculus
HCT 116 CVCL_0291 Colon carcinoma Homo sapiens
                    Experimental
                    Result(s)		 The synergistic actions of Gamma-T3 and ATST could be attributed to their mediation of 3-hydroxy-3-methyl-glutaryl-CoA reductase, and the subsequent inhibition of protein geranylgeranylation.
          Tretinoin      Homo sapiens     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [9]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression CDH2  Molecule Info 
Pathway MAP
                    In-vivo Model MOG35-55 in female C57BL/6 mice were used in this study.
                    Experimental
                    Result(s)		 Combined atorvastatin and ATRA have immunomodulatory synergistic benefits.
    β. A List of Natural Product(s) Able to Decrease the Adverse Effect of This Drug
          Glatiramer acetate      Homo sapiens     Click to Show/Hide the Molecular Data of This NP
                 Decreasing Adverse Drug Reaction     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [10]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression IL10  Molecule Info 
Pathway MAP
Down-regulation Expression IL12A  Molecule Info 
Pathway MAP
Down-regulation Expression TNF  Molecule Info 
Pathway MAP
                    In-vivo Model Female (PL/J * SJL/J)mice were immunized with MBP Ac1-11 (100 ug) to establish the animal model.
                    Experimental
                    Result(s)		 Monocytes treated with the combination of suboptimal doses of atorvastatin and GA secreted an antiinflammatory type II cytokine pattern and, when used as APCs, promoted Th2 differentiation of naive myelin-specific T cells.
Target and Pathway
Target(s) HMG-CoA reductase (HMGCR)  Molecule Info  [11]
STAT factor 3 (STAT3)  Molecule Info 
BioCyc Superpathway of geranylgeranyldiphosphate biosynthesis I (via mevalonate) Click to Show/Hide
2 Superpathway of cholesterol biosynthesis
3 Mevalonate pathway
KEGG Pathway Terpenoid backbone biosynthesis Click to Show/Hide
2 Metabolic pathways
3 Biosynthesis of antibiotics
4 AMPK signaling pathway
5 Bile secretion
NetPath Pathway IL5 Signaling Pathway Click to Show/Hide
2 TGF_beta_Receptor Signaling Pathway
3 TSH Signaling Pathway
Panther Pathway Cholesterol biosynthesis Click to Show/Hide
Pathwhiz Pathway Steroid Biosynthesis Click to Show/Hide
WikiPathways Statin Pathway Click to Show/Hide
2 Regulation of Lipid Metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha)
3 Activation of Gene Expression by SREBP (SREBF)
4 SREBF and miR33 in cholesterol and lipid homeostasis
5 Integrated Breast Cancer Pathway
6 SREBP signalling
7 Cholesterol Biosynthesis
References
Reference 1 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Reference 2 Promising role of ferulic acid, atorvastatin and their combination in ameliorating high fat diet-induced stress in mice. Life Sci. 2013 May 20;92(17-19):938-49.
Reference 3 Synergistic actions of atorvastatin with gamma-tocotrienol and celecoxib against human colon cancer HT29 and HCT116 cells. Int J Cancer. 2010 Feb 15;126(4):852-63.
Reference 4 Synergistic effect of combined treatment with gamma-tocotrienol and statin on human malignant mesothelioma cells. Cancer Lett. 2013 Oct 1;339(1):116-27.
Reference 5 Synergistic Benefit of Statin and Metformin in Gastrointestinal Malignancies. J Pharm Pract. 2017 Apr;30(2):185-194.
Reference 6 Synergistic inhibition of colon cancer cell growth by a combination of atorvastatin and phloretin. Oncol Lett. 2018 Feb;15(2):1985-1992.
Reference 7 Effectiveness of combination therapy of atorvastatin and non lipid-modifying tanshinone IIA from Danshen in a mouse model of atherosclerosis. Int J Cardiol. 2014 Jul 1;174(3):878-80.
Reference 8 Metabolism of tocotrienols in animals and synergistic inhibitory actions of tocotrienols with atorvastatin in cancer cells. Genes Nutr. 2012 Jan;7(1):11-8.
Reference 9 Synergistic effects of atorvastatin and all-trans retinoic acid in ameliorating animal model of multiple sclerosis. Immunol Invest. 2014;43(1):54-68.
Reference 10 Immunomodulatory synergy by combination of atorvastatin and glatiramer acetate in treatment of CNS autoimmunity. J Clin Invest. 2006 Apr;116(4):1037-44.
Reference 11 Equally potent inhibitors of cholesterol synthesis in human hepatocytes have distinguishable effects on different cytochrome P450 enzymes. Biopharm Drug Dispos. 2000 Dec;21(9):353-64.
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