Drug Information

Drug (ID: DG00427) and It's Reported Resistant Information

• Name: PD131628
• Synonyms: 127967-03-7; PD 131628; UNII-YS492L6CHP; YS492L6CHP; 1,8-Naphthyridine-3-carboxylic acid, 7-[(3S)-3-amino-1-pyrrolidinyl]-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-; (S)-7-(3-Amino-1-pyrrolidinyl)-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid; 7-[(3S)-3-aminopyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,8-naphthyridine-3-carboxylic acid; (S)-7-(3-aminopyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid; 1,8-Naphthyridine-3-carboxylic acid, 7-((3S)-3-amino-1-pyrrolidinyl)-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-; 7-(3-Amino-1-pyrrolidinyl)-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid; CI-990 (Hydrochloride); CHEMBL51678; PD131628 (Hydrochloride); SCHEMBL9838735; DTXSID9074486; PD131628; PD131628-0002B; 1,8-Naphthyridine-3-carboxylic acid, 7-(3-amino-1-pyrrolidinyl)-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-, (S)-; 1-Cyclopropyl-6-fluoro-7-[3beta-amino-1-pyrrolidinyl]-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Pneumonia [ICD-11: CA40]; [1]
• Formula: C16H17FN4O3
• IsoSMILES: C1CN(C[C@H]1N)C2=C(C=C3C(=O)C(=CN(C3=N2)C4CC4)C(=O)O)F
• InChI: 1S/C16H17FN4O3/c17-12-5-10-13(22)11(16(23)24)7-21(9-1-2-9)14(10)19-15(12)20-4-3-8(18)6-20/h5,7-9H,1-4,6,18H2,(H,23,24)/t8-/m0/s1
• InChIKey: MUKSDTOOLRNSIO-QMMMGPOBSA-N
• PubChem CID: 72448

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-12: Respiratory system diseases

Pneumonia [ICD-11: CA40]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: DNA topoisomerase 4 subunit A (PARC) [1]

• Molecule Alteration: Missense mutation; p.D84H (GAT-CAT)
• Resistant Disease: Pneumocystis jirovecii infection [ICD-11: CA40.6]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae strain BM4203-BM4203-R; 1313
• In Vitro Model: Streptococcus pneumoniae strain BM4204-BM4204-R; 1313
• Experiment for Molecule Alteration: Sequence analysis
• Experiment for Drug Resistance: Agar dilution assay
• Mechanism Description: Mutations in parC were detected in the two resistant mutants obtained in vivo (BM4203-R andBM4204-R) as well as in two (BM4203-R1 and BM4203-R2) of the six mutants obtained in vitro. These mutations led to Ser-80-Tyr or Phe or to Asp-84-His substitutions(S. aureus coordinates) that are either identical or similar to those found in low-level-resistant parC mutations of S. aureus:Ser-80-Tyr or Phe and Glu-84-Lys or Leu.

Key Molecule: DNA topoisomerase 4 subunit A (PARC) [1]

• Molecule Alteration: Missense mutation; p.S80Y (TCT-TAT)
• Resistant Disease: Pneumocystis jirovecii infection [ICD-11: CA40.6]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae strain BM4203-BM4203-R; 1313
• In Vitro Model: Streptococcus pneumoniae strain BM4204-BM4204-R; 1313
• Experiment for Molecule Alteration: Sequence analysis
• Experiment for Drug Resistance: Agar dilution assay
• Mechanism Description: Mutations in parC were detected in the two resistant mutants obtained in vivo (BM4203-R andBM4204-R) as well as in two (BM4203-R1 and BM4203-R2) of the six mutants obtained in vitro. These mutations led to Ser-80-Tyr or Phe or to Asp-84-His substitutions(S. aureus coordinates) that are either identical or similar to those found in low-level-resistant parC mutations of S. aureus:Ser-80-Tyr or Phe and Glu-84-Lys or Leu.

Key Molecule: DNA topoisomerase 4 subunit A (PARC) [1]

• Molecule Alteration: Missense mutation; p.S80F (TCT-TTT)
• Resistant Disease: Pneumocystis jirovecii infection [ICD-11: CA40.6]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae strain BM4203-BM4203-R; 1313
• In Vitro Model: Streptococcus pneumoniae strain BM4204-BM4204-R; 1313
• Experiment for Molecule Alteration: Sequence analysis
• Experiment for Drug Resistance: Agar dilution assay
• Mechanism Description: Mutations in parC were detected in the two resistant mutants obtained in vivo (BM4203-R andBM4204-R) as well as in two (BM4203-R1 and BM4203-R2) of the six mutants obtained in vitro. These mutations led to Ser-80-Tyr or Phe or to Asp-84-His substitutions(S. aureus coordinates) that are either identical or similar to those found in low-level-resistant parC mutations of S. aureus:Ser-80-Tyr or Phe and Glu-84-Lys or Leu.

Key Molecule: DNA gyrase subunit A (GYRA) [1]

• Molecule Alteration: Missense mutation; p.S843F (TCC-TTC)
• Resistant Disease: Pneumocystis jirovecii infection [ICD-11: CA40.6]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae strain BM4203-BM4203-R; 1313
• In Vitro Model: Streptococcus pneumoniae strain BM4204-BM4204-R; 1313
• Experiment for Molecule Alteration: Sequence analysis
• Experiment for Drug Resistance: Agar dilution assay
• Mechanism Description: An additional mutant obtained in vitro, BM4205-R3, displayed a higher level of fluoroquinolone resistance and had a mutation in gyrA leading to a Ser-84-Phe change.

References

• Ref 1: Contribution of mutations in gyrA and parC genes to fluoroquinolone resistance of mutants of Streptococcus pneumoniae obtained in vivo and in vitro. Antimicrob Agents Chemother. 1996 Nov;40(11):2505-10. doi: 10.1128/AAC.40.11.2505.