Drug Information

Drug (ID: DG00366) and It's Reported Resistant Information

• Name: Disorazole C1
• Synonyms: Disorazole C1; 158181-52-3
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (3 diseases)
  Breast cancer [ICD-11: 2C60]; [1]
  Cervical cancer [ICD-11: 2C77]; [1]
  Lung cancer [ICD-11: 2C25]; [1]
• Formula: C44H58N2O10
• IsoSMILES: C/C=C/[C@H](O)C([C@H]1OC(=O)C2=COC(=N2)C[C@H](/C=C\\C=C/C=C\\C[C@H](OC(=O)C3=COC(=N3)C[C@H](/C=C\\C=C/C=C\\C1)OC)C([C@@H](O)/C=C/C)(C)C)OC)(C)C
• InChI: 1S/C44H58N2O10/c1-9-21-35(47)43(3,4)37-25-19-15-11-13-17-23-32(52-8)28-40-46-34(30-54-40)42(50)56-38(44(5,6)36(48)22-10-2)26-20-16-12-14-18-24-31(51-7)27-39-45-33(29-53-39)41(49)55-37/h9-24,29-32,35-38,47-48H,25-28H2,1-8H3/b13-11-,14-12-,19-15-,20-16-,21-9+,22-10+,23-17-,24-18-/t31-,32-,35-,36-,37-,38-/m0/s1
• InChIKey: FGVAPNZAWLGHCU-BBJFQTBJSA-N
• PubChem CID: 101668901

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

Lung cancer [ICD-11: 2C25]

Drug Resistance 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; Up-regulation
• Resistant Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: A549/EpoB40 cells; Lung; Homo sapiens (Human); CVCL_4Z15
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: ArrayScan VTi imaging cytometer assay
• Mechanism Description: Compared with wild-type HeLa cells, disorazole C1-resistant HeLa/DZR cells were 34- and 8-fold resistant to disorazole C1 and disorazole A1 growth inhibition. HeLa/DZR cells expressed elevated levels of the drug resistance ATP-binding cassette ABCB1 transporter. The natural product disorazole A1 is not a substrate for the ABCB1 multiple drug resistance transporter. But at least a portion of the disorazole C1 and A1 resistance in HeLa/DZR was due to.

Breast cancer [ICD-11: 2C60]

Drug Resistance 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; Up-regulation
• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: MCF-7/MDR cells; Breast; Homo sapiens (Human); CVCL_0031
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: ArrayScan VTi imaging cytometer assay
• Mechanism Description: Compared with wild-type HeLa cells, disorazole C1-resistant HeLa/DZR cells were 34- and 8-fold resistant to disorazole C1 and disorazole A1 growth inhibition. HeLa/DZR cells expressed elevated levels of the drug resistance ATP-binding cassette ABCB1 transporter. The natural product disorazole A1 is not a substrate for the ABCB1 multiple drug resistance transporter. But at least a portion of the disorazole C1 and A1 resistance in HeLa/DZR was due to.

Cervical cancer [ICD-11: 2C77]

Drug Resistance 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; Up-regulation
• Resistant Disease: Cervical carcinoma [ICD-11: 2C77.1]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Hela cells; Cervix uteri; Homo sapiens (Human); CVCL_0030
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: ArrayScan VTi imaging cytometer assay
• Mechanism Description: Compared with wild-type HeLa cells, disorazole C1-resistant HeLa/DZR cells were 34- and 8-fold resistant to disorazole C1 and disorazole A1 growth inhibition. HeLa/DZR cells expressed elevated levels of the drug resistance ATP-binding cassette ABCB1 transporter. The natural product disorazole A1 is not a substrate for the ABCB1 multiple drug resistance transporter. But at least a portion of the disorazole C1 and A1 resistance in HeLa/DZR was due to.

References

• Ref 1: Identifying a resistance determinant for the antimitotic natural products disorazole C1 and A1. J Pharmacol Exp Ther. 2010 Mar;332(3):906-11. doi: 10.1124/jpet.109.162842. Epub 2009 Dec 15.