Drug Information

Drug (ID: DG01197) and It's Reported Resistant Information

• Name: Tocotrienol
• Synonyms: Tocotrienol; 6829-55-6; 2-methyl-2-[(3E,7E)-4,8,12-trimethyltrideca-3,7,11-trienyl]-3,4-dihydrochromen-6-ol; Tocotrienols; (R)-3,4-Dihydro-2-methyl-2-(4,8,12-trimethyl-3,7,11-tridecatrienyl)-2H-1-benzopyran-6-ol; CCRIS 7711; CHEMBL120643; SCHEMBL1081622; SCHEMBL1448780; DB12647; NCGC00186586-01; Q27236375; 2-methyl-2-[(3E,7E)-4,8,12-trimethyltrideca-3,7,11-trien-1-yl]-3,4-dihydro-2H-1-benzopyran-6-ol; 3,4-Dihydro-2-methyl-2-[(3E,7E)-4,8,12-trimethyl-3,7,11-tridecatrienyl]-2H-1-benzopyran-6-ol
• Indication:
  In total 1 Indication(s)
  Hyperlipidaemia [ICD-11: 5C80]; Approved; [1]
• Target: HMG-CoA reductase (HMGCR); HMDH_HUMAN; [1]
• Formula: C26H38O2
• IsoSMILES: CC(=CCC/C(=C/CC/C(=C/CCC1(CCC2=C(O1)C=CC(=C2)O)C)/C)/C)C
• InChI: 1S/C26H38O2/c1-20(2)9-6-10-21(3)11-7-12-22(4)13-8-17-26(5)18-16-23-19-24(27)14-15-25(23)28-26/h9,11,13-15,19,27H,6-8,10,12,16-18H2,1-5H3/b21-11+,22-13+
• InChIKey: GJJVAFUKOBZPCB-ZGRPYONQSA-N
• PubChem CID: 9929901
• TTD Drug ID: D03VFL
• DrugBank ID: DB12647

Type(s) of Resistant Mechanism of This Drug

  IDUE: Irregularity in Drug Uptake and Drug Efflux

Drug Resistance Data Categorized by Their Corresponding Diseases

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

Breast cancer [ICD-11: 2C60]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [1]

• Molecule Alteration: Expression; Down-regulation
• Sensitive Disease: Breast cancer [ICD-11: 2C60.3]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: NF-KappaB signaling pathway; Inhibition; hsa04064
• In Vitro Model: VCaP cells; Prostate; Homo sapiens (Human); CVCL_2235
• Experiment for Molecule Alteration: Quantitative real-time PCR; Western blot analysis; Reporter gene assay of NF-kappaB transcriptional activity assay; MDR1 promoter reporter assay; P-gp activity assay
• Experiment for Drug Resistance: Reversal effect assay
• Mechanism Description: Gamma-Tocotrienol reverses multidrug resistance of breast cancer cells through the regulation of the gamma-Tocotrienol-NF-kappaB-P-gp axis. gamma-Tocotrienol effectively suppressed mdr1 promoter activity and the efflux of P-gp. gamma-Tocotrienol inhibited NF-kappaB activation and reduced NF-kappaB transcriptional activity.

Key Molecule: Multidrug resistance protein 1 (ABCB1) [1]

• Molecule Alteration: Expression; Down-regulation
• Sensitive Disease: Breast cancer [ICD-11: 2C60.3]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: NF-KappaB signaling pathway; Inhibition; hsa04064
• In Vitro Model: VCaP cells; Prostate; Homo sapiens (Human); CVCL_2235
• Experiment for Molecule Alteration: Quantitative real-time PCR; Western blot analysis; Reporter gene assay of NF-kappaB transcriptional activity assay; MDR1 promoter reporter assay; P-gp activity assay
• Experiment for Drug Resistance: Reversal effect assay
• Mechanism Description: Gamma-Tocotrienol reverses multidrug resistance of breast cancer cells through the regulation of the gamma-Tocotrienol-NF-kappaB-P-gp axis. gamma-Tocotrienol effectively suppressed mdr1 promoter activity and the efflux of P-gp. gamma-Tocotrienol inhibited NF-kappaB activation and reduced NF-kappaB transcriptional activity.

References

• Ref 1: Gamma-Tocotrienol reverses multidrug resistance of breast cancer cells through the regulation of the Gamma-Tocotrienol-NF-kB-P-gp axis .J Steroid Biochem Mol Biol. 2021 May;209:105835. doi: 10.1016/j.jsbmb.2021.105835. Epub 2021 Feb 5. 10.1016/j.jsbmb.2021.105835