Details of the Drug

General Information of Drug (ID: DMNP60F)

Drug Name
Anastrozole
Synonyms
Anastrazole; Anastrole; Anastrozol; Arimidex; Asiolex; Astra brand of anastrozole; AstraZeneca brand of anastrozole; Zeneca brand of anastrozole; ZD 1033; ZD1033; Zeneca ZD 1033; Arimidex (TN); Arimidex (Zeneca); Arimidex, Anastrozole; ZD-1033; Anastrozole [USAN:INN:BAN]; Anastrozole (JAN/USAN/INN); Alpha,alpha,alpha',alpha'-tetramethyl-5(1H-1,2,4-triazol-1-ylmethyl)-m-benzenediacetonitrile; Alpha,alpha,alpha',alpha'-Tetramethyl-5-(1H-1,2,4-triazol-1-ylmethyl)-m-benzenediacetonitrile; 1,3-benzenediacetonitrile, a, a,a', a'-tetramethyl-5-(1H-1,2,4-triazol-1-ylmethyl); 2,2'-(5-(1H-1,2,4-triazol-1-ylmethyl)-1,3-phenylene)bis(2-methylpropionitrile); 2,2'-[5-(1H-1,2,4-triazol-1-ylmethyl)-1,3-phenylene]bis(2-methylpropanenitrile); 2,2'-[5-(1H-1,2,4-triazol-1-ylmethyl)benzene-1,3-diyl]bis(2-methylpropanenitrile); 2-[3-(2-cyanopropan-2-yl)-5-(1,2,4-triazol-1-ylmethyl)phenyl]-2-methylpropanenitrile
Indication
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Approved [1]
Estrogen-receptor positive breast cancer N.A. Approved [2]
Obesity 5B81 Approved [2]
Therapeutic Class
Anticancer Agents
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 293.4
Logarithm of the Partition Coefficient (xlogp) 2.1
Rotatable Bond Count (rotbonds) 4
Hydrogen Bond Donor Count (hbonddonor) 0
Hydrogen Bond Acceptor Count (hbondacc) 4
ADMET Property
Absorption Tmax
The time to maximum plasma concentration (Tmax) is 5 h [3]
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [4]
Bioavailability
80% of drug becomes completely available to its intended biological destination(s) [5]
Elimination
Hepatic metabolism accounts for approximately 85% of anastrozole elimination, and approximately 10% of the administered dosage is eliminated unchanged in the urine [3]
Half-life
The concentration or amount of drug in body reduced by one-half in 50 hours [3]
Metabolism
The drug is metabolized via the liver [6]
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.05692 micromolar/kg/day [7]
Vd
The volume of distribution (Vd) of drug is 3.19 L/kg [8]
Water Solubility
The ability of drug to dissolve in water is measured as 0.5 mg/mL [4]
Adverse Drug Reaction (ADR)
ADR Term Variation Related DOT DOT ID REF
Cardiovascular disorder Not Available AK1 OT614AR3 [9]
Chemical Identifiers
Formula
C17H19N5
IUPAC Name
2-[3-(2-cyanopropan-2-yl)-5-(1,2,4-triazol-1-ylmethyl)phenyl]-2-methylpropanenitrile
Canonical SMILES
CC(C)(C#N)C1=CC(=CC(=C1)CN2C=NC=N2)C(C)(C)C#N
InChI
InChI=1S/C17H19N5/c1-16(2,9-18)14-5-13(8-22-12-20-11-21-22)6-15(7-14)17(3,4)10-19/h5-7,11-12H,8H2,1-4H3
InChIKey
YBBLVLTVTVSKRW-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
2187
ChEBI ID
CHEBI:2704
CAS Number
120511-73-1
DrugBank ID
DB01217
TTD ID
D0W0BF
VARIDT ID
DR00464
INTEDE ID
DR0113
ACDINA ID
D00039
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Aromatase (CYP19A1) TTSZLWK CP19A_HUMAN Inhibitor [10]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Putative sodium-coupled neutral amino acid transporter 7 (SLC38A7) DT2EGUN S38A7_HUMAN Substrate [11]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4)
Main DME 		DE4LYSA CP3A4_HUMAN Substrate [12]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Substrate [12]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Substrate [12]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Substrate [12]
UDP-glucuronosyltransferase 2B7 (UGT2B7) DEB3CV1 UD2B7_HUMAN Substrate [12]
UDP-glucuronosyltransferase 1A3 (UGT1A3) DEF2WXN UD13_HUMAN Substrate [12]
UDP-glucuronosyltransferase 1A4 (UGT1A4)
Main DME 		DELOY3P UD14_HUMAN Substrate []

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Adenylate kinase isoenzyme 1 (AK1) OT614AR3 KAD1_HUMAN Drug Response [9]
Aromatase (CYP19A1) OTZ6XF74 CP19A_HUMAN Gene/Protein Processing [13]
Gap junction alpha-1 protein (GJA1) OTT94MKL CXA1_HUMAN Gene/Protein Processing [14]
NADPH--cytochrome P450 reductase (POR) OTVIDOCH NCPR_HUMAN Gene/Protein Processing [15]
Progesterone receptor (PGR) OT0FZ3QE PRGR_HUMAN Gene/Protein Processing [16]
Proliferation marker protein Ki-67 (MKI67) OTA8N1QI KI67_HUMAN Gene/Protein Processing [17]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Anastrozole
DDI Drug Name DDI Drug ID Severity Mechanism Disease REF
Tucatinib DMBESUA Moderate Decreased metabolism of Anastrozole caused by Tucatinib mediated inhibition of CYP450 enzyme. Breast cancer [2C60-2C6Y] [18]
Coadministration of a Drug Treating the Disease Different from Anastrozole (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Fostamatinib DM6AUHV Moderate Decreased metabolism of Anastrozole caused by Fostamatinib mediated inhibition of CYP450 enzyme. Thrombocytopenia [3B64] [19]

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG
DIG Name DIG ID PubChem CID Functional Classification
Beta-D-lactose E00099 6134 Diluent; Dry powder inhaler carrier; Lyophilization aid
Carmellose sodium E00625 Not Available Disintegrant
Hypromellose E00634 Not Available Coating agent
Lactose monohydrate E00393 104938 Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate E00208 11177 lubricant
Polyethylene glycol 300 E00651 Not Available Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Polyethylene glycol 400 E00653 Not Available Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Polyethylene glycol 6000 E00655 Not Available Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Polysorbate 80 E00665 Not Available Dispersing agent; Emollient; Emulsifying agent; Plasticizing agent; Solubilizing agent; Surfactant; Suspending agent
Povidone E00667 Not Available Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent
Silicon dioxide E00670 Not Available Anticaking agent; Opacifying agent; Viscosity-controlling agent
Titanium dioxide E00322 26042 Coating agent; Colorant; Opacifying agent
Triacetin E00080 5541 Humectant; Plasticizing agent; Solvent
Vinylpyrrolidone E00668 Not Available Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent
⏷ Show the Full List of 14 Pharmaceutical Excipients of This Drug
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Anastrozole 1 mg tablet 1 mg Oral Tablet Oral
Jump to Detail Pharmaceutical Formulation Page of This Drug

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: 5137).
2 Anastrozole FDA Label
3 FDA Approved Drug Products: Arimidex (anastrozole) oral tablets
4 BDDCS applied to over 900 drugs
5 Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
6 Rosenzweig P, Canal M, Patat A, Bergougnan L, Zieleniuk I, Bianchetti G: A review of the pharmacokinetics, tolerability and pharmacodynamics of amisulpride in healthy volunteers. Hum Psychopharmacol. 2002 Jan;17(1):1-13.
7 Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
8 Miyajima M, Kusuhara H, Takahashi K, Takashima T, Hosoya T, Watanabe Y, Sugiyama Y: Investigation of the effect of active efflux at the blood-brain barrier on the distribution of nonsteroidal aromatase inhibitors in the central nervous system. J Pharm Sci. 2013 Sep;102(9):3309-19. doi: 10.1002/jps.23600. Epub 2013 May 27.
9 ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
10 Effective aromatase inhibition by anastrozole in a patient with gonadotropin-independent precocious puberty in McCune-Albright syndrome. J Pediatr Endocrinol Metab. 2002;15 Suppl 3:945-8.
11 Anastrozole Aromatase Inhibitor Plasma Drug Concentration Genome-Wide Association Study: Functional Epistatic Interaction Between SLC38A7 and ALPPL2. Clin Pharmacol Ther. 2019 Jan 16.
12 In vitro and in vivo oxidative metabolism and glucuronidation of anastrozole. Br J Clin Pharmacol. 2010 Dec;70(6):854-69.
13 Aromatase inhibition: translation into a successful therapeutic approach. Clin Cancer Res. 2005 Apr 15;11(8):2809-21. doi: 10.1158/1078-0432.CCR-04-2187.
14 Inhibition of estrogen receptor reduces connexin 43 expression in breast cancers. Toxicol Appl Pharmacol. 2018 Jan 1;338:182-190. doi: 10.1016/j.taap.2017.11.020. Epub 2017 Nov 24.
15 Assessment of Five Pesticides as Endocrine-Disrupting Chemicals: Effects on Estrogen Receptors and Aromatase. Int J Environ Res Public Health. 2022 Feb 10;19(4):1959. doi: 10.3390/ijerph19041959.
16 Aromatase inhibitors: cellular and molecular effects. J Steroid Biochem Mol Biol. 2005 May;95(1-5):83-9. doi: 10.1016/j.jsbmb.2005.04.010.
17 Biomarker changes during neoadjuvant anastrozole, tamoxifen, or the combination: influence of hormonal status and HER-2 in breast cancer--a study from the IMPACT trialists. J Clin Oncol. 2005 Apr 10;23(11):2477-92. doi: 10.1200/JCO.2005.07.559. Epub 2005 Mar 14.
18 Product Information. Tukysa (tucatinib). Seattle Genetics Inc, Bothell, WA.
19 Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.