Drug Information

Drug (ID: DG00281) and It's Reported Resistant Information

• Name: Beta-lapachone
• Synonyms: ARQ 501; SL 11001; A-lapachone; LAPACHONE, BETA; AK-693/21096016; 2,2-dimethyl-3,4-dihydrobenzo[h]chromene-5,6-dione; 3,4-Dihydro-2,2-dimethyl-2H-naphtho(1,2-b)pyran-5,6-dione; 3,4-Dihydro-2,2-dimethyl-2H-naphtho[1,2-B]pyran-5,6-dione
• Indication:
  In total 1 Indication(s)
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; Phase 2; [1]
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
  Brain cancer [ICD-11: 2A00]; [1]
• Target: DNA topoisomerase I (TOP1); TOP1_HUMAN; [1]
• Formula: C15H14O3
• IsoSMILES: CC1(CCC2=C(O1)C3=CC=CC=C3C(=O)C2=O)C
• InChI: 1S/C15H14O3/c1-15(2)8-7-11-13(17)12(16)9-5-3-4-6-10(9)14(11)18-15/h3-6H,7-8H2,1-2H3
• InChIKey: QZPQTZZNNJUOLS-UHFFFAOYSA-N
• PubChem CID: 3885
• ChEBI ID: CHEBI:10429
• TTD Drug ID: D0W0VD
• INTEDE ID: DR1869
• DrugBank ID: DB11948

Type(s) of Resistant Mechanism of This Drug

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

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

Brain cancer [ICD-11: 2A00]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-218-2 [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Glioblastoma [ICD-11: 2A00.02]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: AKT signaling pathway; Inhibition; hsa04151
• In Vitro Model: U251 cells; Brain; Homo sapiens (Human); CVCL_0021
• In Vitro Model: U87 cells; Brain; Homo sapiens (Human); CVCL_0022
• In Vitro Model: U118 cells; Brain; Homo sapiens (Human); CVCL_0633
• In Vitro Model: HA-1800 cells; Brain; Homo sapiens (Human); N.A.
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: CCK8 assay; Soft agar colony formation assay; Wound-healing analysis
• Mechanism Description: miR218-2 promotes glioblastomas growth, invasion and drug resistance by targeting CDC27, and the overexpression of CDC27 counteracted the function of miR218-2 in glioma cells. miR218-2 induces glioma malig.ncy by targeting CDC27, which leads to a decrease in the activation of the APC/C biquitin-proteosome pathway, probably downstream of the TGFbeta signaling pathways.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Cell division cycle protein 27 homolog (CDC27) [1]

• Molecule Alteration: Expression; Down-regulation
• Resistant Disease: Glioblastoma [ICD-11: 2A00.02]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: AKT signaling pathway; Inhibition; hsa04151
• In Vitro Model: U251 cells; Brain; Homo sapiens (Human); CVCL_0021
• In Vitro Model: U87 cells; Brain; Homo sapiens (Human); CVCL_0022
• In Vitro Model: U118 cells; Brain; Homo sapiens (Human); CVCL_0633
• In Vitro Model: HA-1800 cells; Brain; Homo sapiens (Human); N.A.
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Dual luciferase assay; Western blot analysis; Immunohistochemistry (IHC) assay
• Experiment for Drug Resistance: CCK8 assay; Soft agar colony formation assay; Wound-healing analysis
• Mechanism Description: miR218-2 promotes glioblastomas growth, invasion and drug resistance by targeting CDC27, and the overexpression of CDC27 counteracted the function of miR218-2 in glioma cells. miR218-2 induces glioma malig.ncy by targeting CDC27, which leads to a decrease in the activation of the APC/C biquitin-proteosome pathway, probably downstream of the TGFbeta signaling pathways.

References

• Ref 1: mir-218-2 promotes glioblastomas growth, invasion and drug resistance by targeting CDC27. Oncotarget. 2017 Jan 24;8(4):6304-6318. doi: 10.18632/oncotarget.13850.