Drug Information

Drug (ID: DG00403) and It's Reported Resistant Information

• 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
• Indication:
  In total 1 Indication(s)
  Breast cancer [ICD-11: 2C60]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Breast cancer [ICD-11: 2C60]; [2]
• Target: Aromatase (CYP19A1); CP19A_HUMAN; [1]
• Formula: C17H11N5
• IsoSMILES: 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
• PubChem CID: 3902
• ChEBI ID: CHEBI:6413
• TTD Drug ID: D0C1WH
• INTEDE ID: DR0929
• DrugBank ID: DB01006

Type(s) of Resistant Mechanism of This Drug

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

Breast cancer [ICD-11: 2C60]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Estrogen receptor alpha (ESR1) [1]

• Molecule Alteration: Missense mutation; p.Y537N
• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: Sanger sequencing assay; dPCR assay
• Mechanism Description: Acquired mutations in the estrogen-receptor gene ESR1 can be a marker of resistance to aromatase inhibitors in metastatic breast cancer.

Key Molecule: Estrogen receptor alpha (ESR1) [1]

• Molecule Alteration: Missense mutation; p.D538G
• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: Sanger sequencing assay; dPCR assay
• Mechanism Description: Acquired mutations in the estrogen-receptor gene ESR1 can be a marker of resistance to aromatase inhibitors in metastatic breast cancer.

Key Molecule: Estrogen receptor alpha (ESR1) [2], [3]

• Molecule Alteration: Missense mutation; p.Y537S
• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: Droplet digital polymerase chain reaction assay
• Experiment for Drug Resistance: Chest x-ray assay; Computed tomography assay; Magnetic resonance imaging assay; Positron emission tomography assay
• Mechanism Description: We have developed a ddPCR-based method for the sensitive detection and quantification of 4 representative ESR1 mutations, Y537S, Y537N, Y537C, and D538G, in 325 breast cancer specimens, in which 270 primary breast cancer and 55 MBC specimens.

Key Molecule: Estrogen receptor alpha (ESR1) [3]

• Molecule Alteration: Missense mutation; p.Y537N
• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: Droplet digital polymerase chain reaction assay
• Experiment for Drug Resistance: Chest x-ray assay; Computed tomography assay; Magnetic resonance imaging assay; Positron emission tomography assay
• Mechanism Description: We have developed a ddPCR-based method for the sensitive detection and quantification of 4 representative ESR1 mutations, Y537S, Y537N, Y537C, and D538G, in 325 breast cancer specimens, in which 270 primary breast cancer and 55 MBC specimens.

Key Molecule: Estrogen receptor alpha (ESR1) [3]

• Molecule Alteration: Missense mutation; p.Y537C
• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: Droplet digital polymerase chain reaction assay
• Experiment for Drug Resistance: Chest x-ray assay; Computed tomography assay; Magnetic resonance imaging assay; Positron emission tomography assay
• Mechanism Description: We have developed a ddPCR-based method for the sensitive detection and quantification of 4 representative ESR1 mutations, Y537S, Y537N, Y537C, and D538G, in 325 breast cancer specimens, in which 270 primary breast cancer and 55 MBC specimens.

Key Molecule: Estrogen receptor alpha (ESR1) [2]

• Molecule Alteration: Missense mutation; p.L536Q
• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: Whole-genome sequencing assay
• Mechanism Description: Whole-exome and transcriptome analysis showed that six cases harbored mutations of ESR1 affecting its ligand-binding domain (LBD), all of whom had been treated with anti-estrogens and estrogen deprivation therapies.

Key Molecule: Estrogen receptor alpha (ESR1) [2]

• Molecule Alteration: Missense mutation; p.D538G
• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: Whole-genome sequencing assay
• Mechanism Description: Whole-exome and transcriptome analysis showed that six cases harbored mutations of ESR1 affecting its ligand-binding domain (LBD), all of whom had been treated with anti-estrogens and estrogen deprivation therapies.

References

• Ref 1: Short report: Monitoring ESR1 mutations by circulating tumor DNA in aromatase inhibitor resistant metastatic breast cancer. Int J Cancer. 2015 Nov 15;137(10):2513-9. doi: 10.1002/ijc.29612. Epub 2015 Jun 11.
• Ref 2: Activating ESR1 mutations in hormone-resistant metastatic breast cancer. Nat Genet. 2013 Dec;45(12):1446-51. doi: 10.1038/ng.2823. Epub 2013 Nov 3.
• Ref 3: Droplet digital polymerase chain reaction assay for screening of ESR1 mutations in 325 breast cancer specimens. Transl Res. 2015 Dec;166(6):540-553.e2. doi: 10.1016/j.trsl.2015.09.003. Epub 2015 Sep 14.