Drug (ID: DG00185) and It's Reported Resistant Information
Name
Anidulafungin
Synonyms
Ecalta; Eraxis; Anidulafungin [USAN:INN]; Ecalta (TN); Eraxis (TN); LY-303366; V-Echinocandin; VER-002
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Indication
In total 1 Indication(s)
Epilepsy/seizure [ICD-11: 8A61-8A6Z]
Approved
[1]
Structure
Drug Resistance Disease(s)
Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
Candidosis [ICD-11: 1F23]
[2]
Target Fungal 1,3-beta-glucan synthase (Fung GSC2) FKS2_YEAST [1]
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Formula
C58H73N7O17
IsoSMILES
CCCCCOC1=CC=C(C=C1)C2=CC=C(C=C2)C3=CC=C(C=C3)C(=O)N[C@H]4C[C@H]([C@H](NC(=O)[C@@H]5[C@H]([C@H](CN5C(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H]6C[C@H](CN6C(=O)[C@@H](NC4=O)[C@@H](C)O)O)[C@@H]([C@H](C7=CC=C(C=C7)O)O)O)[C@@H](C)O)C)O)O)O
InChI
1S/C58H73N7O17/c1-5-6-7-24-82-40-22-18-35(19-23-40)33-10-8-32(9-11-33)34-12-14-37(15-13-34)51(74)59-41-26-43(70)54(77)63-56(79)47-48(71)29(2)27-65(47)58(81)45(31(4)67)61-55(78)46(50(73)49(72)36-16-20-38(68)21-17-36)62-53(76)42-25-39(69)28-64(42)57(80)44(30(3)66)60-52(41)75/h8-23,29-31,39,41-50,54,66-73,77H,5-7,24-28H2,1-4H3,(H,59,74)(H,60,75)(H,61,78)(H,62,76)(H,63,79)/t29-,30+,31+,39+,41-,42-,43+,44-,45-,46-,47-,48-,49-,50-,54+/m0/s1
InChIKey
JHVAMHSQVVQIOT-MFAJLEFUSA-N
PubChem CID
166548
ChEBI ID
CHEBI:55346
TTD Drug ID
D0F9BY
DrugBank ID
DB00362
Type(s) of Resistant Mechanism of This Drug
  ADTT: Aberration of the Drug's Therapeutic Target
Drug Resistance Data Categorized by Their Corresponding Diseases
ICD-01: Infectious/parasitic diseases
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Candidosis [ICD-11: 1F23]
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: D-glucan-1,3-beta--UDP glucosyltransferase (FKS1) [1]
Molecule Alteration Missense mutation
p.S639P
Resistant Disease Candida auris infection [ICD-11: 1F23.2]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Candida auris strain 498019
Experiment for
Molecule Alteration
DNA sequencing assay
Experiment for
Drug Resistance
Broth microdilution assay
Mechanism Description Sequencing of FkS revealed that 4 isolates contain the amino acid substitution S639P and those isolates exhibit the highest MICs to echinocandins (micafungin, caspofungin, and anidulafungin, CD101).
Key Molecule: D-glucan-1,3-beta--UDP glucosyltransferase (FKS1) [3]
Molecule Alteration Missense mutation
p.S639F
Resistant Disease Candida auris infection [ICD-11: 1F23.2]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Candida auris strain 498019
Experiment for
Molecule Alteration
DNA sequencing assay
Experiment for
Drug Resistance
CLSI broth microdilution method assay
Mechanism Description Echinocandin (micafungin, caspofungin, and anidulafungin) resistance was linked to a novel mutation S639F in FkS1 hot spot region I.
Key Molecule: D-glucan-1,3-beta--UDP glucosyltransferase (FKS1) [4]
Molecule Alteration Missense mutation
p.S652Y
Resistant Disease Candida auris infection [ICD-11: 1F23.2]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Candida auris strain 498019
Experiment for
Molecule Alteration
DNA sequencing assay
Experiment for
Drug Resistance
AFST assay
Mechanism Description One isolate displayed resistance to both echinocandins (micafungin, caspofungin, and anidulafungin) and 5-flucytosine; the former was associated with a serine to tyrosine amino acid substitution in the gene FkS1, and the latter was associated with a phenylalanine to isoleucine substitution in the gene FUR1.
Key Molecule: D-glucan-1,3-beta--UDP glucosyltransferase (FKS1) [5]
Molecule Alteration Missense mutation
p.D632G (c.A1895G)
Resistant Disease Candida glabrata infection [ICD-11: 1F23.3]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Candida glabrata strain 5478
Experiment for
Molecule Alteration
DNA sequencing assay
Experiment for
Drug Resistance
NCCLS method M-27A with broth macrodilution techniques assay
Mechanism Description Fks1p and Fks2p amino acid substitutions confer reduced echinocandin susceptibility in C. glabrata.
Key Molecule: D-glucan-1,3-beta--UDP glucosyltransferase (FKS1) [5]
Molecule Alteration Missense mutation
p.D632E (c.T1896G)
Resistant Disease Candida glabrata infection [ICD-11: 1F23.3]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Candida glabrata strain 5478
Experiment for
Molecule Alteration
DNA sequencing assay
Experiment for
Drug Resistance
NCCLS method M-27A with broth macrodilution techniques assay
Mechanism Description Recently, three reports showed that amino acid substitutions in Fks1p (D632E) and Fks2p (F659V) are responsible for clinical echinocandin resistance in C. glabrata.
Key Molecule: D-glucan-1,3-beta--UDP glucosyltransferase (FKS1) [5]
Molecule Alteration Missense mutation
p.D632Y (c.G1894T)
Resistant Disease Candida glabrata infection [ICD-11: 1F23.3]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Candida glabrata strain 5478
Experiment for
Molecule Alteration
DNA sequencing assay
Experiment for
Drug Resistance
NCCLS method M-27A with broth macrodilution techniques assay
Mechanism Description Fks1p and Fks2p amino acid substitutions confer reduced echinocandin susceptibility in C. glabrata.
Key Molecule: D-glucan-1,3-beta--UDP glucosyltransferase (FKS1) [5]
Molecule Alteration Missense mutation
p.F625S (c.T1874C)
Resistant Disease Candida glabrata infection [ICD-11: 1F23.3]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Candida glabrata strain 5478
Experiment for
Molecule Alteration
DNA sequencing assay
Experiment for
Drug Resistance
NCCLS method M-27A with broth macrodilution techniques assay
Mechanism Description Fks1p and Fks2p amino acid substitutions confer reduced echinocandin susceptibility in C. glabrata.
Key Molecule: D-glucan-1,3-beta--UDP glucosyltransferase (FKS1) [5]
Molecule Alteration Missense mutation
p.S629P (c.T1885C)
Resistant Disease Candida glabrata infection [ICD-11: 1F23.3]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Candida glabrata strain 5478
Experiment for
Molecule Alteration
DNA sequencing assay
Experiment for
Drug Resistance
NCCLS method M-27A with broth macrodilution techniques assay
Mechanism Description Fks1p and Fks2p amino acid substitutions confer reduced echinocandin susceptibility in C. glabrata.
Key Molecule: D-glucan-1,3-beta--UDP glucosyltransferase (FKS1) [5]
Molecule Alteration Missense mutation
p.F659V (c.T1975G)
Resistant Disease Candida glabrata infection [ICD-11: 1F23.3]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Candida glabrata strain 5478
Experiment for
Molecule Alteration
DNA sequencing assay
Experiment for
Drug Resistance
NCCLS method M-27A with broth macrodilution techniques assay
Mechanism Description Recently, three reports showed that amino acid substitutions in Fks1p (D632E) and Fks2p (F659V) are responsible for clinical echinocandin resistance in C. glabrata.
Key Molecule: D-glucan-1,3-beta--UDP glucosyltransferase (FKS1) [5]
Molecule Alteration Missense mutation
p.F659S(c.T1976C)
Resistant Disease Candida glabrata infection [ICD-11: 1F23.3]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Candida glabrata strain 5478
Experiment for
Molecule Alteration
DNA sequencing assay
Experiment for
Drug Resistance
NCCLS method M-27A with broth macrodilution techniques assay
Mechanism Description Fks1p and Fks2p amino acid substitutions confer reduced echinocandin susceptibility in C. glabrata.
Key Molecule: D-glucan-1,3-beta--UDP glucosyltransferase (FKS1) [5]
Molecule Alteration Frameshift mutation
p.F659del(c.1974-CTT-1976)
Resistant Disease Candida glabrata infection [ICD-11: 1F23.3]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Candida glabrata strain 5478
Experiment for
Molecule Alteration
DNA sequencing assay
Experiment for
Drug Resistance
NCCLS method M-27A with broth macrodilution techniques assay
Mechanism Description Fks1p and Fks2p amino acid substitutions confer reduced echinocandin susceptibility in C. glabrata.
Key Molecule: D-glucan-1,3-beta--UDP glucosyltransferase (FKS1) [5]
Molecule Alteration Nonsense mutation
p.R1377STOP (c.A4129T)
Resistant Disease Candida glabrata infection [ICD-11: 1F23.3]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Candida glabrata strain 5478
Experiment for
Molecule Alteration
DNA sequencing assay
Experiment for
Drug Resistance
NCCLS method M-27A with broth macrodilution techniques assay
Mechanism Description Fks1p and Fks2p amino acid substitutions confer reduced echinocandin susceptibility in C. glabrata.
Key Molecule: D-glucan-1,3-beta--UDP glucosyltransferase (FKS1) [2]
Molecule Alteration Missense mutation
p.F655C
Resistant Disease Candida krusei infection [ICD-11: 1F23.4]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Candida krusei strain 4909
Experiment for
Molecule Alteration
DNA sequencing assay
Experiment for
Drug Resistance
Broth macrodilution assay
Mechanism Description A Candida krusei strain from a patient with acute myelogenous leukemia that displayed reduced susceptibility to echinocandin drugs contained a heterozygous mutation, T2080k, in FkS1. The resulting Phe655-Cys substitution altered the sensitivity of glucan synthase to echinocandin drugs, consistent with a common mechanism for echinocandin resistance in Candida spp.
Key Molecule: D-glucan-1,3-beta--UDP glucosyltransferase (FKS1) [6]
Molecule Alteration Missense mutation
p.P660A
Resistant Disease Invasive candidiasis [ICD-11: 1F23.5]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Candida parapsilosis strain 5480
Experiment for
Molecule Alteration
DNA sequencing assay
Experiment for
Drug Resistance
M27-A2 broth dilution method assay
Mechanism Description Overall, these data firmly indicate that a naturally occurring P660A substitution in Fks1p from the C. parapsilosis group accounts for the reduced susceptibility phenotype.
References
Ref 1 Activity of CD101, a long-acting echinocandin, against clinical isolates of Candida auris. Diagn Microbiol Infect Dis. 2018 Mar;90(3):196-197. doi: 10.1016/j.diagmicrobio.2017.10.021. Epub 2017 Nov 7.
Ref 2 Acquired echinocandin resistance in a Candida krusei isolate due to modification of glucan synthase. Antimicrob Agents Chemother. 2007 May;51(5):1876-8. doi: 10.1128/AAC.00067-07. Epub 2007 Feb 26.
Ref 3 A multicentre study of antifungal susceptibility patterns among 350 Candida auris isolates (2009-17) in India: role of the ERG11 and FKS1 genes in azole and echinocandin resistance. J Antimicrob Chemother. 2018 Apr 1;73(4):891-899. doi: 10.1093/jac/dkx480.
Ref 4 Genomic epidemiology of the UK outbreak of the emerging human fungal pathogen Candida auris. Emerg Microbes Infect. 2018 Mar 29;7(1):43. doi: 10.1038/s41426-018-0045-x.
Ref 5 Effect of Candida glabrata FKS1 and FKS2 mutations on echinocandin sensitivity and kinetics of 1,3-beta-D-glucan synthase: implication for the existing susceptibility breakpoint. Antimicrob Agents Chemother. 2009 Sep;53(9):3690-9. doi: 10.1128/AAC.00443-09. Epub 2009 Jun 22.
Ref 6 A naturally occurring proline-to-alanine amino acid change in Fks1p in Candida parapsilosis, Candida orthopsilosis, and Candida metapsilosis accounts for reduced echinocandin susceptibility. Antimicrob Agents Chemother. 2008 Jul;52(7):2305-12. doi: 10.1128/AAC.00262-08. Epub 2008 Apr 28.

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