Drug Information

Drug (ID: DG00122) and It's Reported Resistant Information

• Name: LFF571
• Indication:
  In total 1 Indication(s)
  Clostridium difficile enterocolitis [ICD-11: 1A04]; Phase 2; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Bacterial infection [ICD-11: 1A00-1C4Z]; [1]
• Formula: C60H63N13O13S6
• IsoSMILES: CC1=C2C(=O)N[C@H](C3=NC(=C(S3)COC)C(=O)NCC(=O)N[C@H](C4=NC(=CS4)C5=NC(=CS5)C6=C(C=CC(=N6)C7=NC(=CS7)N(CCCCC(=O)O)C(=O)OC8CCC(CC8)C(=O)O)C9=NC(=CS9)C(=O)N[C@H](C(=N2)S1)CC(=O)NC)[C@H](C1=CC=CC=C1)O)C(C)C
• InChI: 1S/C60H63N13O13S6/c1-28(2)44-58-72-47(39(92-58)23-85-5)51(80)62-22-42(75)69-48(49(78)30-11-7-6-8-12-30)57-67-38(26-89-57)55-65-36(24-88-55)46-33(53-66-37(25-87-53)50(79)64-35(21-41(74)61-4)56-71-45(29(3)91-56)52(81)70-44)18-19-34(63-46)54-68-40(27-90-54)73(20-10-9-13-43(76)77)60(84)86-32-16-14-31(15-17-32)59(82)83/h6-8,11-12,18-19,24-28,31-32,35,44,48-49,78H,9-10,13-17,20-23H2,1-5H3,(H,61,74)(H,62,80)(H,64,79)(H,69,75)(H,70,81)(H,76,77)(H,82,83)/t31 ,32 ,35-,44-,48-,49-/m0/s1
• InChIKey: GNLYKLDXQZHYTR-QWSGWXDSSA-N
• PubChem CID: 42638236
• TTD Drug ID: D08VWO
• DrugBank ID: DB13013

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

Bacterial infection [ICD-11: 1A00-1C4Z]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Elongation factor Tu (TUF) [1]

• Molecule Alteration: Missense mutation; p.G260E
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Clostridium difficile strain ATCC 43255; 499175
• In Vitro Model: Clostridium difficile strain NB95002; 1496
• In Vitro Model: Clostridium difficile strain NB95026; 1496
• In Vitro Model: Clostridium difficile strain NB95031; 1496
• In Vitro Model: Clostridium difficile strain NB95047; 1496
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Selection on inhibitory concentrations of LFF571 resulted in a substitution at the C. difficile residue analogous to G257 in E. coli EF-Tu.All mutants exhibited tufB mutation G782A, resulting in amino acid substitution G260E; NB95013-JAL0759 harbored the G782A change in both tufA and tufB.

References

• Ref 1: Mechanism of action of and mechanism of reduced susceptibility to the novel anti-Clostridium difficile compound LFF571. Antimicrob Agents Chemother. 2012 Aug;56(8):4463-5. doi: 10.1128/AAC.06354-11. Epub 2012 May 29.