Drug Details

General Information of the Drug (ID: DR1575)
Name
Letrozole
Synonyms
Femara; Femera; Letoval; Letrozol; Novartis Brand of Letrozole; CGS 20267; CGS-20267; FEM-345; Femara (TN); Letrozole [USAN:INN]; CGS 20267, Femara, Piroxicam, Letrozole; Letrozole (JAN/USP/INN); 1-[Bis-(4-cyanophenyl)methyl]-1,2,4-triazole; 1-[bis(4-cyanophenyl)methyl]-1,2,4-triazole; 4,4'-((1h-1,2,4-triazol-1-yl)methylene)dibenzonitrile; 4,4'-(1H-1,2,4-Triazol-1-ylmethylene)dibenzonitrile; 4,4'-(1H-1,2,4-triazol-1-yl-methylene)-bis(benzonitrile); 4,4'-(1H-1,2,4-triazol-1-ylmethanediyl)dibenzonitrile; 4,4'-(1H-1,2,4-triazol-1-ylmethylene)bis-Benzonitrile Letrozole; 4,4'-(1h-1,2,4-triazol-1-ylmethylene) bis-benzonitrile; 4,4'-(1h-1,2,4-triazol-1-ylmethylene)bis-benzonitrile; 4,4'-(1h-1,2,4-triazol-1-ylmethylene)bisbenzonitrile; 4-[(4-cyanophenyl)-(1,2,4-triazol-1-yl)methyl]benzonitrile
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Molecular Type
Small molecule
Disease Breast cancer [ICD-11: 2C60] Approved [1]
Structure
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2D MOL

3D MOL

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Formula
C17H11N5
PubChem CID
3902
Canonical SMILES
C1=CC(=CC=C1C#N)C(C2=CC=C(C=C2)C#N)N3C=NC=N3
InChI
1S/C17H11N5/c18-9-13-1-5-15(6-2-13)17(22-12-20-11-21-22)16-7-3-14(10-19)4-8-16/h1-8,11-12,17H
InChIKey
HPJKCIUCZWXJDR-UHFFFAOYSA-N
CAS Number
CAS 112809-51-5
ChEBI ID
CHEBI:6413
TTD Drug ID
D0C1WH
DrugBank ID
DB01006
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Natural Product(s) Able to Enhance the Efficacy of This Drug
          Curcumin      Hellenia speciosa     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     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 BCL-2  Molecule Info 
Pathway MAP
                    In-vivo Model RL-952 cells at logarithmic growth phase were suspended to a density of 5*107/mL and subcutaneously injected into ovariectomized nude mice through the dorsal skin of each side (0.1 mL/mouse, containing 5*106 cells).
                    Experimental
                    Result(s)		 Treatment with either letrozole or curcumin could inhibit the xenografted endometrial tumor growth via inducing apoptosis in tumor cells. Combination of letrozole and curcumin further strengthened the inhibitory effect on tumor growth.
          Testosterone      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 [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vivo Model A total of 48 adult (8 weeks old) male Sprague-Dawley rats with mean weight of 250-300 gr were enrolled in this study.
                    Experimental
                    Result(s)		 Both testosterone and its combination with letrozole increased lumbar and femoral BMD of orchiectomized rats, with a higher increase in lumbar BMD in O + T group.
Target and Pathway
Target(s) Aromatase (CYP19A1)  Molecule Info  [4]
BioCyc Superpathway of steroid hormone biosynthesis Click to Show/Hide
2 Estradiol biosynthesis II
3 Estradiol biosynthesis I
KEGG Pathway Steroid hormone biosynthesis Click to Show/Hide
2 Metabolic pathways
3 Ovarian steroidogenesis
NetPath Pathway FSH Signaling Pathway Click to Show/Hide
Panther Pathway Androgen/estrogene/progesterone biosynthesis Click to Show/Hide
Pathwhiz Pathway Androgen and Estrogen Metabolism Click to Show/Hide
Reactome Endogenous sterols Click to Show/Hide
WikiPathways Metapathway biotransformation Click to Show/Hide
2 Tryptophan metabolism
3 Oxidation by Cytochrome P450
4 Ovarian Infertility Genes
5 Metabolism of steroid hormones and vitamin D
6 FSH signaling pathway
7 Integrated Breast Cancer Pathway
8 Phase 1 - Functionalization of compounds
References
Reference 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: 5209).
Reference 2 Aromatase inhibitor letrozole in synergy with curcumin in the inhibition of xenografted endometrial carcinoma growth. Int J Gynecol Cancer. 2009 Oct;19(7):1248-52.
Reference 3 The effect of testosterone itself and in combination with letrozole on bone mineral density in male rats. J Bone Miner Metab. 2019 Jul;37(4):668-675.
Reference 4 Aromatase inhibitors--theoretical concept and present experiences in the treatment of endometriosis. Zentralbl Gynakol. 2003 Jul-Aug;125(7-8):247-51.
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