Drug Information

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
• Indication:
  In total 1 Indication(s)
  Epilepsy/seizure [ICD-11: 8A61-8A6Z]; Approved; [1]
• 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]
• 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

Candidosis [ICD-11: 1F23]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

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.