Drug Information

Drug (ID: DG00361) and It's Reported Resistant Information

• Name: Brefeldin A
• Synonyms: Brefeldin A; Ascotoxin; Synergisidin; Decumbin; Nectrolide; Cyanein; 20350-15-6; Cyanaein; Brefeldin-A; Brefeldin A prodrug; (+)-Brefeldin A; Bredfeldin A; UNII-XG0D35F9K6; NSC-89671; MLS001074108; XG0D35F9K6; CHEBI:48080; SMR000653527; Pfizer B 174987; (1R,2E,6S,10E,11aS,13S,14aR)-1,13-dihydroxy-6-methyl-1,6,7,8,9,11a,12,13,14,14a-decahydro-4H-cyclopenta[f]oxacyclotridecin-4-one; Antibiotic from Penicillium cyaneum; NSC 56310; SR-01000000180; MLS002701937; MLS002702862; CCRIS 9386; NSC107456; NSC244390; 1,6,7,8,9,11a,12,13,14,14a-Decahydro-1,13-dihydroxy-6-methyl-4H-cyclopent[f]oxacyclotridecin-4-one; NSC 89671; B 174987; Probes1_000313; SCHEMBL29267; MLS002153500; CHEMBL19980; PFIZER B174987; BDBM97307; cid_5287620; DTXSID00880041; HMS2233O20; 60132-23-2; BFA; 2283AH; NSC-56310; s7046; ZINC12371944; AM84700; CCG-208161; CS-3783; DB07348; NSC 107456; NSC 244390; NSC-107456; NSC-244390; NCGC00022909-02; (1S,2E,7S,10E,12R,13R,15S)-12,15-dihydroxy-7-methyl-8-oxabicyclo[11.3.0]hexadeca-2,10-dien-9-one; 4H-Cyclopent(f)oxacyclotridecin-4-one,1,6,7,8,9,11a-beta,12,13,14,14a-alpha-decahydro-1-beta-13-alpha-dihydroxy-6-beta-methyl-; HY-16592; SMR000768725; TOXIC SOLID, N.O.S. (BREFELDIN A); SW220015-1; C73840; Q168790; SR-01000000180-5; SR-01000000180-7; W-201775; BRD-K77841042-001-14-1; Brefeldin A, from Penicillium brefeldianum, >=99% (HPLC and TLC); Brefeldin A, >=99% (HPLC and TLC), BioXtra, for molecular biology; (1S,2E,7S,10E,12R,13R,15S)-7-methyl-12,15-bis(oxidanyl)-8-oxabicyclo[11.3.0]hexadeca-2,10-dien-9-one; 11006-23-8; 4H-Cyclopent(f)oxacyclotridecin-4-one, 1,6,7,8,9,11a-beta,12,13,14,14a-alpha-decahydro-1-beta-13-alpha-dihydroxy-6-beta-methyl-; 4H-Cyclopent[f]oxacyclotridecin-4-one,6,7,8,9,11a,12,13, 14,14a-decahydro-1,13-dihydroxy-6-methyl-, [1R-(1R*,2E,6S*, 10E,11aS*,13S*,14aR*)]-; 4H-Cyclopent[f]oxacyclotridecin-4-one,6,7,8,9,11a.beta.,12,13,14,14a.alpha.-decahydro- 1.beta.,13.alpha.-dihydroxy-6.beta.-methyl-; Brefeldin A, from Penicillium brefeldianum, Ready Made Solution, 10 mg/mL in DMSO, 0.2 mum filtered; Pfizer B 174987 4H-Cyclopent[f]oxacyclotridecin-4-one,6,7,8,9,11a,12,13,14,14a-decahydro-1,13-dihydroxy-6-methyl-, (1R,2E,6S,10E,11aS,13S,14aR)-
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Validated by in-vivo Model for This Drug (1 diseases)
  Fungal infection [ICD-11: 1F29-1F2F]; [1]
• Formula: C16H24O4
• IsoSMILES: C[C@H]1CCC/C=C/[C@@H]2C[C@@H](C[C@H]2[C@@H](/C=C/C(=O)O1)O)O
• InChI: 1S/C16H24O4/c1-11-5-3-2-4-6-12-9-13(17)10-14(12)15(18)7-8-16(19)20-11/h4,6-8,11-15,17-18H,2-3,5,9-10H2,1H3/b6-4+,8-7+/t11-,12+,13-,14+,15+/m0/s1
• InChIKey: KQNZDYYTLMIZCT-KQPMLPITSA-N
• PubChem CID: 5287620
• DrugBank ID: DB07348

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-01: Infectious/parasitic diseases

Candidosis [ICD-11: 1F23]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Pleiotropic ABC efflux transporter of multiple drugs CDR1 (CDR1) [2]

• Molecule Alteration: Deletion mutation; Deleteion
• Sensitive Disease: Recurrent oropharyngeal candidiasis [ICD-11: 1F23.6]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Candida albicans strain DSY448; 5476
• 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 delta cdr1 mutant was also hypersusceptible to other antifungal agents (terbinafine and amorolfine) and to different metabolic inhibitors (cycloheximide, brefeldin A, and fluphenazine).

Fungal infection [ICD-11: 1F29-1F2F]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Brefeldin A resistance protein (BFR1) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Schizosaccharomyces pombe infection [ICD-11: 1F29-1F2F]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Schizosaccharomyces pombe BAP1; 4896
• In Vitro Model: Schizosaccharomyces pombe BAP3; 4896
• In Vitro Model: Schizosaccharomyces pombe FWP1; 4896
• Experiment for Molecule Alteration: Northern blot analysis
• Mechanism Description: Here we present the characterization of one of these genes, hba2, which encodes a novel S. pombe protein that shares significant sequence similarity to members of the ATP-binding cassette superfamily of transport proteins. Examination of hba2 expression determined that this gene is overexpressed in mutant strains resistant to brefeldin A due to mutations in the negative regulator crm1 (bar1) gene or the bar2 gene. The increase of hba2 expression was independent of the pap1 transcription factor which is repressed by wild typ.

References

• Ref 1: Characterization of a novel Schizosaccharomyces pombe multidrug resistance transporter conferring brefeldin A resistance. Biochem Biophys Res Commun. 1995 Aug 15;213(2):410-8. doi: 10.1006/bbrc.1995.2147.
• 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.