Molecule Information

General Information of the Molecule (ID: Mol00724)

• Name: Pleiotropic ABC efflux transporter of multiple drugs CDR /Multidrug resistance protein 1 (CDR1/ABCB1) ,Candida albicans
• Molecule Type: Protein
• Gene Name: BCR/ABL
• Uniprot ID: CDR1_CANAL/MDR1_CANAL

Kingdom: Fungi
Phylum: Ascomycota
Class: Saccharomycetes
Order: Saccharomycetales
Family: Debaryomycetaceae
Genus: Candida
Species: Candida albicans

Type(s) of Resistant Mechanism of This Molecule

  IDUE: Irregularity in Drug Uptake and Drug Efflux

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Brentuximab vedotin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Hodgkin lymphoma [1]

• Resistant Disease: Hodgkin lymphoma [ICD-11: 2B30.0]
• Resistant Drug: Brentuximab vedotin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: L428 cells; Lymph; Homo sapiens (Human); CVCL_1361
• In Vitro Model: KM-H2 cells; Lymph; Homo sapiens (Human); CVCL_1330
• In Vivo Model: Female NSG mouse model; Mus musculus
• Experiment for Molecule Alteration: Flow cytometry
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: Competitive inhibition of MDR1 restored sensitivity to BV in our BV-resistant cell lines by increasing intracellular MMAE levels, and potentiated BV activity in BV-resistant HL tumors in a human xenograft mouse model.

Investigative Drug(s) 2 drug(s) in total

Cerulenin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Recurrent oropharyngeal candidiasis [2]

• Sensitive Disease: Recurrent oropharyngeal candidiasis [ICD-11: 1F23.6]
• Sensitive Drug: Cerulenin
• Molecule Alteration: Deletion mutation; Deleteion
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Candida tropicalis strain DSY468; 5482
• Experiment for Molecule Alteration: PCR; Southern blotting analysis; Northern blottling analysis
• Experiment for Drug Resistance: Growth differences between the different C. albicans strains assay
• Mechanism Description: The double delta cdr1 and delta ben mutant DSY468 showed increased growth inhibition in plates containing cyclo-heximide and cerulenin compared with the growth of strain CAF2-1 and of the delta ben mutant DSY465. A slight increase in the level of inhibition of DSY468 compared with that of the delta cdr1 mutant DSY448 was observed with cycloheximide, whereas this effect was more severe with cerulenin.

Cycloheximide

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Recurrent oropharyngeal candidiasis [2]

• Sensitive Disease: Recurrent oropharyngeal candidiasis [ICD-11: 1F23.6]
• Sensitive Drug: Cycloheximide
• Molecule Alteration: Deletion mutation; Deleteion
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Candida tropicalis strain DSY468; 5482
• Experiment for Molecule Alteration: PCR; Southern blotting analysis; Northern blottling analysis
• Experiment for Drug Resistance: Growth differences between the different C. albicans strains assay
• Mechanism Description: The double delta cdr1 and delta ben mutant DSY468 showed increased growth inhibition in plates containing cyclo-heximide and cerulenin compared with the growth of strain CAF2-1 and of the delta ben mutant DSY465. A slight increase in the level of inhibition of DSY468 compared with that of the delta cdr1 mutant DSY448 was observed with cycloheximide, whereas this effect was more severe with cerulenin.

References

• Ref 1: Inhibition of MDR1 Overcomes Resistance to Brentuximab Vedotin in Hodgkin LymphomaClin Cancer Res. 2020 Mar 1;26(5):1034-1044. doi: 10.1158/1078-0432.CCR-19-1768. Epub 2019 Dec 6.
• Ref 2: Susceptibilities of Candida albicans multidrug transporter mutants to various antifungal agents and other metabolic inhibitors. Antimicrob Agents Chemother. 1996 Oct;40(10):2300-5. doi: 10.1128/AAC.40.10.2300.