Drug Information

Drug (ID: DG02002) and It's Reported Resistant Information

• Name: Endoxifen
• Synonyms: Endoxifen|112093-28-4|Z-Endoxifen|4-Hydroxy-N-desmethyltamoxifen|Endoxifen Z-Isomer|N-Desmethyl-4-hydroxytamoxifen|(Z)-Endoxifen|110025-28-0|(E/Z)-Endoxifen|NSC-749798|4OHNDtam|ENDOXIFEN [WHO-DD]|(Z)-4-Hydroxy-N-desmethyl Tamoxifen (contains up to 10% E isomer)|Endoxifen (Z-isomer)|4-[(Z)-1-[4-[2-(methylamino)ethoxy]phenyl]-2-phenylbut-1-enyl]phenol|4-Hydroxy-N-desmethyl-tamoxifen|CHEBI:80555|46AF8680RC|NSC 749798|MFCD09840374|4-[(~{Z})-1-[4-[2-(methylamino)ethoxy]phenyl]-2-phenylbut-1-enyl]phenol|4-[(1Z)-1-{4-[2-(methylamino)ethoxy]phenyl}-2-phenylbut-1-en-1-yl]phenol|Phenol, 4-(1-(4-(2-(methylamino)ethoxy]phenyl)-2-phenyl-1-butenyl)-, (Z)-|UNII-46AF8680RC|4-hydroxy-N-desmethyl tamoxifen|Endoxifen?|4-hydroxy-N-desmethyltamoxifen, (Z)-isomer|(Z)-4-(1-(4-(2-(methylamino)ethoxy)phenyl)-2-phenylbut-1-en-1-yl)phenol|4-((~(Z))-1-(4-(2-(methylamino)ethoxy)phenyl)-2-phenylbut-1-enyl)phenol|4-(1-(4-(2-(methylamino)ethoxy)phenyl)-2-phenylbut-1-en-1-yl)phenol|EndoxifenZ-Isomer|phenol, 4-((1Z)-1-(4-(2-(methylamino)ethoxy)phenyl)-2-phenyl-1-buten-1-yl)-|4-[1-[4-[2-(Methylamino)ethoxy]phenyl]-2-phenyl-1-butenyl]phenol; (E/Z)-Endoxifen; 4OHNDtam;|Endoxifen(E/Z=1:1)|CHEMBL1093458|SCHEMBL10107920|GTPL10203|DTXSID80149880|EX-A645|MHJBZVSGOZTKRH-IZHYLOQSSA-N|Phenol, 4-[(1Z)-1-[4-[2-(methylamino)ethoxy]phenyl]-2-phenyl-1-buten-1-yl]-|BCP15866|EX-A1970|4-[1-[4-[2-(methylamino)ethoxy]phenyl]-2-phenylbut-1-enyl]phenol|BDBM50435003|HY-18719E|NSC746494|NSC749798|NSC777380|NSC833479|AKOS030526256|FE15969|NSC-746494|NSC-777380|NSC-833479|NCGC00386714-01|AC-36810|BE172975|BS-42369|CS-0028594|NS00093647|EN300-822190|BRD-K62752296-003-01-3|Q27149598|N-Desmethyl-4-hydroxy tamoxifen(approx. 1:1 e/z mixture)|(Z)-4-Hydroxy-N-desmethyl tamoxifen(contains up to 10% e isomer)|(E/Z)-4-(1-(4-(2-(methylamino)ethoxy)phenyl)-2-phenylbut-1-enyl)phenol|(Z)-4-(1-(4-(2-(methylamino)ethoxy)phenyl)-2-phenylbut-1-enyl)phenol|(E/Z)-4-[1-[4-[2-(Methylamino)ethoxy]phenyl]-2-phenyl-1-buten-1-yl]-phenol;4-Hydroxy-N-desmethyltamoxifen
• Indication:
  In total 1 Indication(s)
  . .; .
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
  Breast cancer [ICD-11: 2C60]; [1]
• Formula: C25H27NO2
• IsoSMILES: CC/C(=C(\C1=CC=C(C=C1)O)/C2=CC=C(C=C2)OCCNC)/C3=CC=CC=C3
• InChI: InChI=1S/C25H27NO2/c1-3-24(19-7-5-4-6-8-19)25(20-9-13-22(27)14-10-20)21-11-15-23(16-12-21)28-18-17-26-2/h4-16,26-27H,3,17-18H2,1-2H3/b25-24-
• InChIKey: MHJBZVSGOZTKRH-IZHYLOQSSA-N
• PubChem CID: 10090750
• ChEBI ID: CHEBI:80555
• VARIDT ID: DR01627

Type(s) of Resistant Mechanism of This Drug

  MRAP: Metabolic Reprogramming via Altered Pathways

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

Metabolic Reprogramming via Altered Pathways (MRAP)

Key Molecule: AMP-activated kinase alpha-2 (PRKAA2) [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Estrogen receptor (ER)-positive breast cancer [ICD-11: 2C60.6]
• Molecule Alteration: Autophosphorylation; T172
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: ER+ MCF7 BC cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: TRC cells; Breast; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: Therefore, our results indicate increased activation of AKT and AMPK with metabolic reprogramming and increased autophagy in TAM-resistant cells. Simultaneous inhibition of AKT and FAO/autophagy is necessary to fully sensitize resistant cells to endoxifen.

Key Molecule: AKT serine/threonine kinase (AKT) [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Estrogen receptor (ER)-positive breast cancer [ICD-11: 2C60.6]
• Molecule Alteration: Autophosphorylation; S473
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: ER+ MCF7 BC cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: TRC cells; Breast; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: Therefore, our results indicate increased activation of AKT and AMPK with metabolic reprogramming and increased autophagy in TAM-resistant cells. Simultaneous inhibition of AKT and FAO/autophagy is necessary to fully sensitize resistant cells to endoxifen.

References

• Ref 1: Fatty acid oxidation and autophagy promote endoxifen resistance and counter the effect of AKT inhibition in ER-positive breast cancer cells. J Mol Cell Biol. 2021 Sep 11;13(6):433-444.