Drug Information

Drug (ID: DG00367) and It's Reported Resistant Information

• Name: Disorazole A1
• Synonyms: Disorazole A1; CHEMBL501853; SCHEMBL13593476
• 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: C43H54N2O10
• IsoSMILES: C/C=C/[C@@H](C(C)(C)[C@@H]1C/C=C\\C=C/C=C/[C@@H](CC2=NC(=CO2)C(=O)O[C@@H](C/C=C\\[C@@H]3[C@@H](O3)/C=C/C=C\\C4=NC(=CO4)C(=O)O1)C(C)(C)[C@H](/C=C/C)O)OC)O
• InChI: 1S/C43H54N2O10/c1-8-18-34(46)42(3,4)36-23-14-12-10-11-13-20-29(50-7)26-39-45-31(28-52-39)41(49)55-37(43(5,6)35(47)19-9-2)24-17-22-33-32(53-33)21-15-16-25-38-44-30(27-51-38)40(48)54-36/h8-22,25,27-29,32-37,46-47H,23-24,26H2,1-7H3/b11-10-,14-12-,18-8+,19-9+,20-13+,21-15+,22-17-,25-16-/t29-,32-,33+,34-,35-,36-,37-/m0/s1
• InChIKey: FRFRWOXVYJSPCG-YEYPPUHMSA-N
• PubChem CID: 44566233

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.