Drug Information

Drug (ID: DG00126) and It's Reported Resistant Information

• Name: Clotrimazole
• Synonyms: Canesten; Canestene; Canestine; Canifug; Chlotrimazole; Cimitidine; Clomatin; Clotrimaderm; Clotrimazol; Clotrimazolum; Clotrimeizol; Cutistad; Empecid; Esparol; FemCare; Gynix; Kanesten; Klotrimazole; Lotrimax; Lotrimin; Monobaycuten; Mycelax; Mycelex; Mycofug; Mycosporin; Mykosporin; Nalbix; Pedisafe; Rimazole; Stiemazol; Tibatin; Trimysten; Canesten Cream; Canesten Solution; Clotrimazole Schering Brand; Desamix F; Fem Care; Gyne lotrimin; Lotrimin AF Cream; Lotrimin AF Lotion; Lotrimin AF Solution; Lotrimin Af; Lotrimin Cream; Lotrimin Lotion; Lotrimin Solution; Mycelex Cream; Mycelex G; Mycelex OTC; Mycelex Solution; Mycelex Troches; Mycelex Twin Pack; Myclo Cream; Myclo Solution; Myclo Spray Solution; Schering Brand of Clotrimazole; B 5097; Bay b 9057; Bayer Brand 1 of Clotrimazole; Bayer Brand 2 of Clotrimazole; C 6019; FB 5097; FB b 5097; Mycelex 7; Trivagizole 3; Bay-B 5097; Candid Vaginal (TN); Candinil (TN); Canesten (TN); Canesten 1-Day Therapy; Canesten 3-Day Therapy; Canesten 6-Day Therapy; Clobrate VT (TN); Clotrimazol [INN-Spanish]; Clotrimazolum [INN-Latin]; DRG-0072; Gino-Lotremine; Gyne-Lotrimin; Gyne-Lotrimin 3; Gyne-Lotrimin 3 Combination Pack; Gyne-Lotrimin Combination Pack; Lotrimin (TN); Lotrimin AF Jock-Itch Cream; Mono-baycuten; Mycelex (TN); Mycelex-7; Mycelex-7 Combination Pack; Mycelex-G; Mycelex: MycosporinRimazole; Myclo-Gyne; Neo-Zol Cream; Pan-Fungex; Cancap-VT (TN); Candid - V Gel (TN); Canesten 1-Day Cream Combi-Pak; Canesten Combi-Pak 1-Day Therapy; Canesten Combi-Pak 3-Day Therapy; Clotrimazole (JP15/USP/INN); Clotrimazole [USAN:INN:BAN:JAN]; (Chlorotrityl)imidazole; 1-(o-Chlorotrityl)imidazole
• Indication:
  In total 1 Indication(s)
  Fungal infection [ICD-11: 1F29-1F2F]; Approved; [1]
• 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]
• Target: C-X-C chemokine receptor type 2 (CXCR2); CXCR2_HUMAN; [1]
• Formula: C22H17ClN2
• IsoSMILES: C1=CC=C(C=C1)C(C2=CC=CC=C2)(C3=CC=CC=C3Cl)N4C=CN=C4
• InChI: 1S/C22H17ClN2/c23-21-14-8-7-13-20(21)22(25-16-15-24-17-25,18-9-3-1-4-10-18)19-11-5-2-6-12-19/h1-17H
• InChIKey: VNFPBHJOKIVQEB-UHFFFAOYSA-N
• PubChem CID: 2812
• ChEBI ID: CHEBI:3764
• TTD Drug ID: D09GOS
• VARIDT ID: DR00574
• INTEDE ID: DR0362
• DrugBank ID: DB00257

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

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

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Pleiotropic ABC efflux transporter of multiple drugs (PDR5) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Fungal infection [ICD-11: 1F29-1F2F]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Yeast detapdr5 strain R-1; N.A.; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Determined spectrophotometrically assay
• Mechanism Description: Pdr5p is an important ABC transporter. It is a 170 kDa plasma membrane protein with 1511 amino acids in a single polypeptide chain. It effluxes a wide range of structurally and functionally diverse compounds, such as rhodamine 6-G, tetrapropyltin, cycloheximide, tritylimidazole, and clotrimazole. Loss-of-function mutations in the pdr5 gene cause profound drug hypersensitivity, while overexpression creates multidrug hyperresi.

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 (PDR5) [1]

• Molecule Alteration: Missense mutation; p.T257I
• Sensitive Disease: Fungal infection [ICD-11: 1F29-1F2F]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Yeast detapdr5 strain R-1; N.A.; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Determined spectrophotometrically assay
• Mechanism Description: The double mutation Gly905Ser/Gly908Ser that is located in the Walker A motif of NBD2. Apparently the double mutation disrupts the ATP catalytic cycle since the cells bearing it are sensitive to all Pdr5p drugs. Other NBD mutations result in a differential sensitivity. Those mutations include Asn242Lys, Thr257Ile, Gly302Asp, Gly1009Cys, Gly1040Asp, Ser1048Val, and His1.

Key Molecule: Pleiotropic ABC efflux transporter of multiple drugs (PDR5) [1]

• Molecule Alteration: Missense mutation; p.S1048V
• Sensitive Disease: Fungal infection [ICD-11: 1F29-1F2F]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Yeast detapdr5 strain R-1; N.A.; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Determined spectrophotometrically assay
• Mechanism Description: The double mutation Gly905Ser/Gly908Ser that is located in the Walker A motif of NBD2. Apparently the double mutation disrupts the ATP catalytic cycle since the cells bearing it are sensitive to all Pdr5p drugs. Other NBD mutations result in a differential sensitivity. Those mutations include Asn242Lys, Thr257Ile, Gly302Asp, Gly1009Cys, Gly1040Asp, Ser1048Val, and His1.

Key Molecule: Pleiotropic ABC efflux transporter of multiple drugs (PDR5) [1]

• Molecule Alteration: Missense mutation; p.N242K
• Sensitive Disease: Fungal infection [ICD-11: 1F29-1F2F]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Yeast detapdr5 strain R-1; N.A.; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Determined spectrophotometrically assay
• Mechanism Description: The double mutation Gly905Ser/Gly908Ser that is located in the Walker A motif of NBD2. Apparently the double mutation disrupts the ATP catalytic cycle since the cells bearing it are sensitive to all Pdr5p drugs. Other NBD mutations result in a differential sensitivity. Those mutations include Asn242Lys, Thr257Ile, Gly302Asp, Gly1009Cys, Gly1040Asp, Ser1048Val, and His1.

Key Molecule: Pleiotropic ABC efflux transporter of multiple drugs (PDR5) [1]

• Molecule Alteration: Missense mutation; p.H1068A
• Sensitive Disease: Fungal infection [ICD-11: 1F29-1F2F]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Yeast detapdr5 strain R-1; N.A.; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Determined spectrophotometrically assay
• Mechanism Description: The double mutation Gly905Ser/Gly908Ser that is located in the Walker A motif of NBD2. Apparently the double mutation disrupts the ATP catalytic cycle since the cells bearing it are sensitive to all Pdr5p drugs. Other NBD mutations result in a differential sensitivity. Those mutations include Asn242Lys, Thr257Ile, Gly302Asp, Gly1009Cys, Gly1040Asp, Ser1048Val, and His1.

Key Molecule: Pleiotropic ABC efflux transporter of multiple drugs (PDR5) [1]

• Molecule Alteration: Missense mutation; p.G908S
• Sensitive Disease: Fungal infection [ICD-11: 1F29-1F2F]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Yeast detapdr5 strain R-1; N.A.; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Determined spectrophotometrically assay
• Mechanism Description: The double mutation Gly905Ser/Gly908Ser that is located in the Walker A motif of NBD2. Apparently the double mutation disrupts the ATP catalytic cycle since the cells bearing it are sensitive to all Pdr5p drugs. Other NBD mutations result in a differential sensitivity. Those mutations include Asn242Lys, Thr257Ile, Gly302Asp, Gly1009Cys, Gly1040Asp, Ser1048Val, and His1.

Key Molecule: Pleiotropic ABC efflux transporter of multiple drugs (PDR5) [1]

• Molecule Alteration: Missense mutation; p.G905S+p.G908S
• Sensitive Disease: Fungal infection [ICD-11: 1F29-1F2F]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Yeast detapdr5 strain R-1; N.A.; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Determined spectrophotometrically assay
• Mechanism Description: The double mutation Gly905Ser/Gly908Ser that is located in the Walker A motif of NBD2. Apparently the double mutation disrupts the ATP catalytic cycle since the cells bearing it are sensitive to all Pdr5p drugs. Other NBD mutations result in a differential sensitivity. Those mutations include Asn242Lys, Thr257Ile, Gly302Asp, Gly1009Cys, Gly1040Asp, Ser1048Val, and His1.

Key Molecule: Pleiotropic ABC efflux transporter of multiple drugs (PDR5) [1]

• Molecule Alteration: Missense mutation; p.G905S
• Sensitive Disease: Fungal infection [ICD-11: 1F29-1F2F]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Yeast detapdr5 strain R-1; N.A.; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Determined spectrophotometrically assay
• Mechanism Description: The double mutation Gly905Ser/Gly908Ser that is located in the Walker A motif of NBD2. Apparently the double mutation disrupts the ATP catalytic cycle since the cells bearing it are sensitive to all Pdr5p drugs. Other NBD mutations result in a differential sensitivity. Those mutations include Asn242Lys, Thr257Ile, Gly302Asp, Gly1009Cys, Gly1040Asp, Ser1048Val, and His1.

Key Molecule: Pleiotropic ABC efflux transporter of multiple drugs (PDR5) [1]

• Molecule Alteration: Missense mutation; p.G302D
• Sensitive Disease: Fungal infection [ICD-11: 1F29-1F2F]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Yeast detapdr5 strain R-1; N.A.; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Determined spectrophotometrically assay
• Mechanism Description: The double mutation Gly905Ser/Gly908Ser that is located in the Walker A motif of NBD2. Apparently the double mutation disrupts the ATP catalytic cycle since the cells bearing it are sensitive to all Pdr5p drugs. Other NBD mutations result in a differential sensitivity. Those mutations include Asn242Lys, Thr257Ile, Gly302Asp, Gly1009Cys, Gly1040Asp, Ser1048Val, and His1.

Key Molecule: Pleiotropic ABC efflux transporter of multiple drugs (PDR5) [1]

• Molecule Alteration: Missense mutation; p.G1040D
• Sensitive Disease: Fungal infection [ICD-11: 1F29-1F2F]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Yeast detapdr5 strain R-1; N.A.; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Determined spectrophotometrically assay
• Mechanism Description: The double mutation Gly905Ser/Gly908Ser that is located in the Walker A motif of NBD2. Apparently the double mutation disrupts the ATP catalytic cycle since the cells bearing it are sensitive to all Pdr5p drugs. Other NBD mutations result in a differential sensitivity. Those mutations include Asn242Lys, Thr257Ile, Gly302Asp, Gly1009Cys, Gly1040Asp, Ser1048Val, and His1.

Key Molecule: Pleiotropic ABC efflux transporter of multiple drugs (PDR5) [1]

• Molecule Alteration: Missense mutation; p.G1009C
• Sensitive Disease: Fungal infection [ICD-11: 1F29-1F2F]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Yeast detapdr5 strain R-1; N.A.; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Determined spectrophotometrically assay
• Mechanism Description: The double mutation Gly905Ser/Gly908Ser that is located in the Walker A motif of NBD2. Apparently the double mutation disrupts the ATP catalytic cycle since the cells bearing it are sensitive to all Pdr5p drugs. Other NBD mutations result in a differential sensitivity. Those mutations include Asn242Lys, Thr257Ile, Gly302Asp, Gly1009Cys, Gly1040Asp, Ser1048Val, and His1.

Key Molecule: Pleiotropic ABC efflux transporter of multiple drugs (PDR5) [1]

• Molecule Alteration: Missense mutation; p.E1289K+p.Y1311S
• Sensitive Disease: Fungal infection [ICD-11: 1F29-1F2F]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Yeast detapdr5 strain R-1; N.A.; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Determined spectrophotometrically assay
• Mechanism Description: The double mutation Gly905Ser/Gly908Ser that is located in the Walker A motif of NBD2. Apparently the double mutation disrupts the ATP catalytic cycle since the cells bearing it are sensitive to all Pdr5p drugs. Other NBD mutations result in a differential sensitivity. Those mutations include Asn242Lys, Thr257Ile, Gly302Asp, Gly1009Cys, Gly1040Asp, Ser1048Val, and His1.

References

• Ref 1: Toward understanding the mechanism of action of the yeast multidrug resistance transporter Pdr5p: a molecular modeling study. J Struct Biol. 2011 Feb;173(2):333-44. doi: 10.1016/j.jsb.2010.10.012. Epub 2010 Oct 27.