Drug Information

Drug (ID: DG00302) and It's Reported Resistant Information

• Name: Ge2270a
• Synonyms: GE 2770; GE-2270; 134861-34-0; SCHEMBL12519961; CHEBI:29584; LS-187584; LS-186934
• Indication:
  In total 1 Indication(s)
  Bacterial infection [ICD-11: 1A00-1C4Z]; Phase 1; [1]
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Validated by in-vivo Model for This Drug (1 diseases)
  Escherichia coli intestinal infection [ICD-11: 1A03]; [1]
• Target: Plasmodium Elongation factor 1-alpha 1 (Malaria MEF-1); EF1A_PLAFK; [1]
• Formula: C56H55N15O10S6
• IsoSMILES: CC1=C2C(=O)NC(C3=NC(=C(S3)COC)C(=O)NCC(=O)NC(C4=NC(=CS4)C5=NC(=CS5)C6=C(C=CC(=N6)C7=NC(=CS7)C8=NC(CO8)C(=O)N9CCCC9C(=O)N)C3=NC(=CS3)C(=O)NC(C(=N2)S1)CC(=O)NC)C(C1=CC=CC=C1)O)C(C)C
• InChI: 1S/C56H55N15O10S6/c1-24(2)39-55-70-42(36(87-55)19-80-5)47(77)59-17-38(73)67-43(44(74)26-10-7-6-8-11-26)54-66-34(23-85-54)52-63-31(20-83-52)41-27(50-64-32(21-82-50)46(76)61-29(16-37(72)58-4)53-69-40(25(3)86-53)48(78)68-39)13-14-28(60-41)51-65-33(22-84-51)49-62-30(18-81-49)56(79)71-15-9-12-35(71)45(57)75/h6-8,10-11,13-14,20-24,29-30,35,39,43-44,74H,9,12,15-19H2,1-5H3,(H2,57,75)(H,58,72)(H,59,77)(H,61,76)(H,67,73)(H,68,78)
• InChIKey: JMDULECOHIXMNX-UHFFFAOYSA-N
• PubChem CID: 16129640
• ChEBI ID: CHEBI:29584
• TTD Drug ID: D0Y3XA
• DrugBank ID: DB02975

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

Escherichia coli intestinal infection [ICD-11: 1A03]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

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

• Molecule Alteration: Missense mutation; p.G257S
• Resistant Disease: Escherichia coli infection [ICD-11: 1A03.0]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli strain; 562
• Mechanism Description: The antibiotic GE2270A prevents stable complex formation between elongation factor Tu (EF-Tu) and aminoacyl-tRNA (aatRNA). In Escherichia coli we characterized two mutant EF-Tu species with either G257S or G275A that lead to high GE2270A resistance in poly(Phe) synthesis, which at least partially explains the high resistance of EF-Tu1 from GE2270A producer Planobispora rosea to its own antibiotic.

Key Molecule: Elongation factor Tu 2 (TUFB) [1]

• Molecule Alteration: Missense mutation; p.G257S
• Resistant Disease: Escherichia coli infection [ICD-11: 1A03.0]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli strain; 562
• Mechanism Description: The antibiotic GE2270A prevents stable complex formation between elongation factor Tu (EF-Tu) and aminoacyl-tRNA (aatRNA). In Escherichia coli we characterized two mutant EF-Tu species with either G257S or G275A that lead to high GE2270A resistance in poly(Phe) synthesis, which at least partially explains the high resistance of EF-Tu1 from GE2270A producer Planobispora rosea to its own antibiotic.

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

• Molecule Alteration: Missense mutation; p.G275A
• Resistant Disease: Escherichia coli infection [ICD-11: 1A03.0]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli strain; 562
• Mechanism Description: The antibiotic GE2270A prevents stable complex formation between elongation factor Tu (EF-Tu) and aminoacyl-tRNA (aatRNA). In Escherichia coli we characterized two mutant EF-Tu species with either G257S or G275A that lead to high GE2270A resistance in poly(Phe) synthesis, which at least partially explains the high resistance of EF-Tu1 from GE2270A producer Planobispora rosea to its own antibiotic.

Key Molecule: Elongation factor Tu 2 (TUFB) [1]

• Molecule Alteration: Missense mutation; p.G275A
• Resistant Disease: Escherichia coli infection [ICD-11: 1A03.0]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli strain; 562
• Mechanism Description: The antibiotic GE2270A prevents stable complex formation between elongation factor Tu (EF-Tu) and aminoacyl-tRNA (aatRNA). In Escherichia coli we characterized two mutant EF-Tu species with either G257S or G275A that lead to high GE2270A resistance in poly(Phe) synthesis, which at least partially explains the high resistance of EF-Tu1 from GE2270A producer Planobispora rosea to its own antibiotic.

References

• Ref 1: GE2270A-resistant mutations in elongation factor Tu allow productive aminoacyl-tRNA binding to EF-Tu.GTP.GE2270A complexes. J Mol Biol. 2000 Dec 15;304(5):995-1005. doi: 10.1006/jmbi.2000.4260.