Drug Information

Drug (ID: DG01850) and It's Reported Resistant Information

• Name: DX-8951
• Synonyms: BCP32858; FT-0777984; Exatecan derivative for ADC;Exatecan derivative; DX-8951 derivative; DX-8951; DX8951; Trastuzumab Deruxtecan (DS-8201a)
• Indication:
  In total 1 Indication(s)
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (2 diseases)
  Breast cancer [ICD-11: 2C60]; [2]
  Gastric cancer [ICD-11: 2B72]; [3]
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
  Breast cancer [ICD-11: 2C60]; [3]
• Target: DNA topoisomerase I (TOP1); TOP1_HUMAN; [1]
• Formula: 3
• IsoSMILES: CCC1(C2=C(COC1=O)C(=O)N3CC4=C5C(CCC6=C5C(=CC(=C6C)F)N=C4C3=C2)NC(=O)CO)O
• InChI: InChI=1S/C26H24FN3O6/c1-3-26(35)15-6-19-23-13(8-30(19)24(33)14(15)10-36-25(26)34)22-17(28-20(32)9-31)5-4-12-11(2)16(27)7-18(29-23)21(12)22/h6-7,17,31,35H,3-5,8-10H2,1-2H3,(H,28,32)
• InChIKey: PLXLYXLUCNZSAA-UHFFFAOYSA-N
• PubChem CID: 146160902
• DrugBank ID: DB16301

Type(s) of Resistant Mechanism of This Drug

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  RTDM: Regulation by the Disease Microenvironment

Drug Resistance Data Categorized by Their Corresponding Diseases

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

Gastric cancer [ICD-11: 2B72]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: HOX transcript antisense RNA (HOTAIR) [3]

• Molecule Alteration: Up-regulation; Interaction
• Resistant Disease: Gastric adenocarcinoma [ICD-11: 2B72.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Gastric cancers tissue; N.A.
• Experiment for Molecule Alteration: Luciferase assay; Western bloting analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: HOTAIR can not only promote tumor proliferation, but also enhances the resistance of tumor cells to drugs.

Breast cancer [ICD-11: 2C60]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: HOX transcript antisense RNA (HOTAIR) [3]

• Molecule Alteration: Up-regulation; Expression
• Resistant Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SK-BR-3 cells; Pleural effusion; Homo sapiens (Human); CVCL_0033
• In Vivo Model: Female BALB/c mice model; Mus musculus
• Experiment for Molecule Alteration: Knockdown assay
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: Down-regulation of long non-coding RNA HOTAIR sensitizes breast cancer to trastuzumab.

Key Molecule: TINCR ubiquitin domain containing (TINCR) [1]

• Molecule Alteration: Up-regulation; Interaction
• Resistant Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: qRT-PCR; Western bloting analysis; Knockdown assay; Overexpression assay; ChIP assay; RIP experiments assay
• Mechanism Description: Activation of LncRNA TINCR by H3K27 acetylation promotes Trastuzumab resistance and epithelial-mesenchymal transition by targeting MicroRNA-125b in breast Cancer.

Regulation by the Disease Microenvironment (RTDM)

Key Molecule: AFAP1 antisense RNA 1 (AFAP1-AS1) [2]

• Molecule Alteration: Up-regulation; Interaction
• Resistant Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: BT474 cells; Breast; Homo sapiens (Human); CVCL_0179
• In Vitro Model: SK-BR-3 cells; Pleural effusion; Homo sapiens (Human); CVCL_0033
• In Vivo Model: Male BALB/c nude mice model; Mus musculus
• Experiment for Molecule Alteration: Knockdown assay; Microarray assay; Immunoprecipitation; FISH assay; qRT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Exosomal AFAP1-AS1 could induce trastuzumab resistance through associating with AUF1 and promoting ERBB2 translation. Therefore, AFAP1-AS1 level may be useful for prediction of trastuzumab resistance and breast cancer treatment.

References

• Ref 1: Morphine post-conditioning-induced up-regulation of lncRNA TINCR protects cardiomyocytes from ischemia-reperfusion injury via inhibiting degradation and ubiquitination of FGF1QJM. 2020 Dec 1;113(12):859-869. doi: 10.1093/qjmed/hcaa088.
• Ref 2: Exosome-mediated lncRNA AFAP1-AS1 promotes trastuzumab resistance through binding with AUF1 and activating ERBB2 translationMol Cancer. 2020 Feb 5;19(1):26. doi: 10.1186/s12943-020-1145-5.
• Ref 3: A Compound AC1Q3QWB Selectively Disrupts HOTAIR-Mediated Recruitment of PRC2 and Enhances Cancer Therapy of DZNepTheranostics. 2019 Jun 24;9(16):4608-4623. doi: 10.7150/thno.35188. eCollection 2019.