Drug Information

Drug (ID: DG00156) and It's Reported Resistant Information
Name
Ceftobiprole
Synonyms
BAL 9141; BAL 9141-000; BAL-9141; Ro 63-9141; Ro-63-9141; Ro-63-9141/000; (6R,7R)-7-[[(2Z)-2-(5-amino-1,2,4-thiadiazol-3-ylidene)-2-nitrosoacetyl]amino]-8-oxo-3-[(E)-[2-oxo-1-[(3R)-pyrrolidin-3-yl]pyrrolidin-3-ylidene]methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
    Click to Show/Hide
Indication
In total 2 Indication(s)
Pneumonia [ICD-11: CA40]
Phase 3
[1], [2], [3], [4], [5], [6]
Skin and skin-structure infection [ICD-11: 1F28-1G0Z]
Phase 3
[1], [2], [3], [4], [5], [6]
Structure
Drug Resistance Disease(s)
Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
Pneumonia [ICD-11: CA40]
[1], [2], [3]
Target Bacterial Penicillin binding protein (Bact PBP) NOUNIPROTAC [1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
C20H22N8O6S2
IsoSMILES
C1CNC[C@@H]1N2CC/C(=C\\C3=C(N4[C@@H]([C@@H](C4=O)NC(=O)/C(=N\\O)/C5=NSC(=N5)N)SC3)C(=O)O)/C2=O
InChI
1S/C20H22N8O6S2/c21-20-24-14(26-36-20)11(25-34)15(29)23-12-17(31)28-13(19(32)33)9(7-35-18(12)28)5-8-2-4-27(16(8)30)10-1-3-22-6-10/h5,10,12,18,22,34H,1-4,6-7H2,(H,23,29)(H,32,33)(H2,21,24,26)/b8-5+,25-11-/t10-,12-,18-/m1/s1
InChIKey
VOAZJEPQLGBXGO-SDAWRPRTSA-N
PubChem CID
135413542
ChEBI ID
CHEBI:140407
TTD Drug ID
D0CI9T
DrugBank ID
DB04918
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
Click to Show/Hide the Resistance Disease of This Class
Pneumonia [ICD-11: CA40]
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Penicillin-binding protein 2X (PBP2X) [1], [2], [3]
Resistant Disease Community-acquired pneumonia [ICD-11: CA40.2]
 Disease Info 
Molecule Alteration Missense mutation
p.M339F
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 2.66  Å
PDB: 5OJ0
Mutant Type Structure Method: X-ray diffraction Resolution: 2.42  Å
PDB: 1PYY
   Download The Information of Sequence       Download The Structure File   
RMSD: 2.25
TM score: 0.91175
Amino acid change:
M339F
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
G
G
50
|
T
T
G
G
T
T
R
R
F
F
G
G
T
T
D
D
L
L
A
A
60
|
K
K
E
E
A
A
K
K
K
K
V
V
H
H
Q
Q
T
T
T
T
70
|
R
R
T
T
V
V
P
P
A
A
K
K
R
R
G
G
T
T
I
I
80
|
Y
Y
D
D
R
R
N
N
G
G
V
V
P
P
I
I
A
A
E
E
90
|
D
D
A
A
T
T
S
S
Y
Y
N
N
V
V
Y
Y
A
A
V
V
100
|
I
I
D
D
E
E
N
N
Y
Y
K
K
S
S
A
A
T
T
G
G
110
|
K
K
I
I
L
L
Y
Y
V
V
E
E
K
K
T
T
Q
Q
F
F
120
|
N
N
K
K
V
V
A
A
E
E
V
V
F
F
H
H
K
K
Y
Y
130
|
L
L
D
D
M
M
E
E
E
E
S
S
Y
Y
V
V
R
R
E
E
140
|
Q
Q
L
L
S
S
Q
Q
P
P
N
N
L
L
K
K
Q
Q
V
V
150
|
S
S
F
F
G
G
A
A
K
K
G
G
N
N
G
G
I
I
T
T
160
|
Y
Y
A
A
N
N
M
M
M
M
S
S
I
I
K
K
K
K
E
E
170
|
L
L
E
E
A
A
A
A
E
E
V
V
K
K
G
G
I
I
D
D
180
|
F
F
T
T
T
T
S
S
P
P
N
N
R
R
S
S
Y
Y
P
P
190
|
N
N
G
G
Q
Q
F
F
A
A
S
S
S
S
F
F
I
I
G
G
200
|
L
L
A
A
Q
Q
L
L
H
H
E
E
N
N
E
E
D
D
G
G
210
|
S
S
K
K
S
S
L
L
L
L
G
G
T
T
S
S
G
G
M
M
220
|
E
E
S
S
S
S
L
L
N
N
S
S
I
I
L
L
A
A
G
G
230
|
T
T
D
D
G
G
I
I
I
I
T
T
Y
Y
E
E
K
K
D
D
240
|
R
R
L
L
G
G
N
N
I
I
V
V
P
P
G
G
T
T
E
E
250
|
Q
Q
V
V
S
S
Q
Q
R
R
T
T
M
M
D
D
G
G
K
K
260
|
D
D
V
V
Y
Y
T
T
T
T
I
I
S
S
S
S
P
P
L
L
270
|
Q
Q
S
S
F
F
M
M
E
E
T
T
Q
Q
M
M
D
D
A
A
280
|
F
F
Q
Q
E
E
K
K
V
V
K
K
G
G
K
K
Y
Y
M
M
290
|
T
T
A
A
T
T
L
L
V
V
S
S
A
A
K
K
T
T
G
G
300
|
E
E
I
I
L
L
A
A
T
T
T
T
Q
Q
R
R
P
P
T
T
310
|
F
F
D
D
A
A
D
D
T
T
K
K
E
E
G
G
I
I
T
T
320
|
E
E
D
D
F
F
V
V
W
W
R
R
D
D
I
I
L
L
Y
Y
330
|
Q
Q
S
S
N
N
Y
Y
E
E
P
P
G
G
S
S
T
A
M
F
340
|
K
K
V
V
M
M
M
M
L
L
A
A
A
A
A
A
I
I
D
D
350
|
N
N
N
N
T
T
F
F
P
P
G
G
G
G
E
E
V
V
F
F
360
|
N
N
S
S
S
S
E
E
L
L
K
K
I
I
A
A
D
D
A
A
370
|
T
T
I
I
R
R
D
D
W
W
D
D
V
V
N
N
E
E
G
G
380
|
L
L
T
T
G
G
G
G
R
R
M
M
M
M
T
T
F
F
S
S
390
|
Q
Q
G
G
F
F
A
A
H
H
S
S
S
S
N
N
V
V
G
G
400
|
M
M
T
T
L
L
L
L
E
E
Q
Q
K
K
M
M
G
G
D
D
410
|
A
A
T
T
W
W
L
L
D
D
Y
Y
L
L
N
N
R
R
F
F
420
|
K
K
F
F
G
G
V
V
P
P
T
T
R
R
F
F
G
G
L
L
430
|
T
T
D
D
E
E
Y
Y
A
A
G
G
Q
Q
L
L
P
P
A
A
440
|
D
D
N
N
I
I
V
V
N
N
I
I
A
A
Q
Q
S
S
S
S
450
|
F
F
G
G
Q
Q
G
G
I
I
S
S
V
V
T
T
Q
Q
T
T
460
|
Q
Q
M
M
I
I
R
R
A
A
F
F
T
T
A
A
I
I
A
A
470
|
N
N
D
D
G
G
V
V
M
M
L
L
E
E
P
P
K
K
F
F
480
|
I
I
S
S
A
A
I
I
Y
Y
D
D
P
P
N
N
D
D
Q
Q
490
|
T
T
A
A
R
R
K
K
S
S
Q
Q
K
K
E
E
I
I
V
V
500
|
G
G
N
N
P
P
V
V
S
S
K
K
D
D
A
A
A
A
S
S
510
|
L
L
T
T
R
R
T
T
N
N
M
M
V
V
L
L
V
V
G
G
520
|
T
T
D
D
P
P
V
V
Y
Y
G
G
T
T
M
M
Y
Y
N
N
530
|
H
H
S
S
T
T
G
G
K
K
P
P
T
T
V
V
T
T
V
V
540
|
P
P
G
G
Q
Q
N
N
V
V
A
A
L
L
K
K
S
S
G
G
550
|
T
T
A
A
Q
Q
I
I
A
A
D
D
E
E
K
K
N
N
G
G
560
|
G
G
Y
Y
L
L
V
V
G
G
L
L
T
T
D
D
Y
Y
I
I
570
|
F
F
S
S
A
A
V
V
S
S
M
M
S
S
P
P
A
A
E
E
580
|
N
N
P
P
D
D
F
F
I
I
L
L
Y
Y
V
V
T
T
V
V
590
|
Q
Q
Q
Q
P
P
E
E
H
H
Y
Y
S
S
G
G
I
I
Q
Q
600
|
L
L
G
G
E
E
F
F
A
A
N
N
P
P
I
I
L
L
E
E
610
|
R
R
A
A
S
S
A
A
M
M
K
K
D
D
S
S
L
L
N
N
620
|
L
L
Q
Q
T
T
T
T
A
A
K
K
A
A
L
L
E
E
Q
Q
630
|
V
V
S
S
Q
Q
Q
Q
S
S
P
P
Y
Y
P
P
M
M
P
P
640
|
S
S
V
V
K
K
D
D
I
I
S
S
P
P
G
G
D
D
L
L
650
|
A
A
E
E
E
E
L
L
R
R
R
R
N
N
L
L
V
V
Q
Q
660
|
P
P
I
I
V
V
V
V
G
G
T
T
G
G
T
T
K
K
I
I
670
|
K
K
N
N
S
S
S
S
A
A
E
E
E
E
G
G
K
K
N
N
680
|
L
L
A
A
P
P
N
N
Q
Q
Q
Q
V
V
L
L
I
I
L
L
690
|
S
S
D
D
K
K
A
A
E
E
E
E
V
V
P
P
D
D
M
M
700
|
Y
Y
G
G
W
W
T
T
K
K
E
E
T
T
A
A
E
E
T
T
710
|
L
L
A
A
K
K
W
W
L
L
N
N
I
I
E
E
L
L
E
E
720
|
F
F
Q
Q
G
G
S
S
G
G
S
S
T
T
V
V
Q
Q
K
K
730
|
Q
Q
D
D
V
V
R
R
A
A
N
N
T
T
A
A
I
I
K
K
740
|
D
D
I
I
K
K
K
K
I
I
T
T
L
L
T
T
L
L
G
G
750
|
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model Streptococcus pneumoniae isolates 1313
Experiment for
Molecule Alteration		 Genome sequence assay
Experiment for
Drug Resistance		 MIC assay
Mechanism Description Beta-Lactam resistance in S. pneumoniae is caused by mutations in the penicillin-binding domains of one or more of its six penicillin-binding proteins (PBPs) resulting from point mutations or mosaic genes. Altered PBP 1a, PBP 2x, and PBP 2b are the most important PBPs for Beta-lactam resistance among clinical isolates.
Key Molecule: Penicillin-binding protein 2X (PBP2X) [1], [2], [3]
Resistant Disease Community-acquired pneumonia [ICD-11: CA40.2]
 Disease Info 
Molecule Alteration Missense mutation
p.I371T
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Streptococcus pneumoniae isolates 1313
Experiment for
Molecule Alteration		 Genome sequence assay
Experiment for
Drug Resistance		 MIC assay
Mechanism Description Beta-Lactam resistance in S. pneumoniae is caused by mutations in the penicillin-binding domains of one or more of its six penicillin-binding proteins (PBPs) resulting from point mutations or mosaic genes. Altered PBP 1a, PBP 2x, and PBP 2b are the most important PBPs for Beta-lactam resistance among clinical isolates.
Key Molecule: Penicillin-binding protein 2X (PBP2X) [1], [2], [3]
Resistant Disease Community-acquired pneumonia [ICD-11: CA40.2]
 Disease Info 
Molecule Alteration Missense mutation
p.R384G
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Streptococcus pneumoniae isolates 1313
Experiment for
Molecule Alteration		 Genome sequence assay
Experiment for
Drug Resistance		 MIC assay
Mechanism Description Beta-Lactam resistance in S. pneumoniae is caused by mutations in the penicillin-binding domains of one or more of its six penicillin-binding proteins (PBPs) resulting from point mutations or mosaic genes. Altered PBP 1a, PBP 2x, and PBP 2b are the most important PBPs for Beta-lactam resistance among clinical isolates.
Key Molecule: Penicillin-binding protein 2X (PBP2X) [1], [2], [3]
Resistant Disease Community-acquired pneumonia [ICD-11: CA40.2]
 Disease Info 
Molecule Alteration Missense mutation
p.M400T
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Streptococcus pneumoniae isolates 1313
Experiment for
Molecule Alteration		 Genome sequence assay
Experiment for
Drug Resistance		 MIC assay
Mechanism Description Beta-Lactam resistance in S. pneumoniae is caused by mutations in the penicillin-binding domains of one or more of its six penicillin-binding proteins (PBPs) resulting from point mutations or mosaic genes. Altered PBP 1a, PBP 2x, and PBP 2b are the most important PBPs for Beta-lactam resistance among clinical isolates.
Key Molecule: Penicillin-binding protein 2X (PBP2X) [1], [2], [3]
Resistant Disease Community-acquired pneumonia [ICD-11: CA40.2]
 Disease Info 
Molecule Alteration Missense mutation
STMK motif p.M>F
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Streptococcus pneumoniae isolates 1313
Experiment for
Molecule Alteration		 Genome sequence assay
Experiment for
Drug Resistance		 MIC assay
Mechanism Description Beta-Lactam resistance in S. pneumoniae is caused by mutations in the penicillin-binding domains of one or more of its six penicillin-binding proteins (PBPs) resulting from point mutations or mosaic genes. Altered PBP 1a, PBP 2x, and PBP 2b are the most important PBPs for Beta-lactam resistance among clinical isolates.
Key Molecule: Penicillin-binding protein 1A (PBP1A) [1], [2], [3]
Resistant Disease Community-acquired pneumonia [ICD-11: CA40.2]
 Disease Info 
Molecule Alteration Missense mutation
STMK motif p.T >A +SRNVP motif p.P >T
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Streptococcus pneumoniae isolates 1313
Experiment for
Molecule Alteration		 Genome sequence assay
Experiment for
Drug Resistance		 MIC assay
Mechanism Description Beta-Lactam resistance in S. pneumoniae is caused by mutations in the penicillin-binding domains of one or more of its six penicillin-binding proteins (PBPs) resulting from point mutations or mosaic genes. Altered PBP 1a, PBP 2x, and PBP 2b are the most important PBPs for Beta-lactam resistance among clinical isolates.
Key Molecule: Penicillin-binding protein 2B (PBP2B) [1], [2], [3]
Resistant Disease Community-acquired pneumonia [ICD-11: CA40.2]
 Disease Info 
Molecule Alteration Missense mutation
p.KTGTA motif p.A >G
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Streptococcus pneumoniae isolates 1313
Experiment for
Molecule Alteration		 Genome sequence assay
Experiment for
Drug Resistance		 MIC assay
Mechanism Description Beta-Lactam resistance in S. pneumoniae is caused by mutations in the penicillin-binding domains of one or more of its six penicillin-binding proteins (PBPs) resulting from point mutations or mosaic genes. Altered PBP 1a, PBP 2x, and PBP 2b are the most important PBPs for Beta-lactam resistance among clinical isolates.
References
Ref 1 Amino acid substitutions in mosaic penicillin-binding protein 2 associated with reduced susceptibility to cefixime in clinical isolates of Neisseria gonorrhoeae. Antimicrob Agents Chemother. 2006 Nov;50(11):3638-45. doi: 10.1128/AAC.00626-06. Epub 2006 Aug 28.
Ref 2 Resistance to Beta-Lactams in Neisseria ssp Due to Chromosomally Encoded Penicillin-Binding Proteins. Antibiotics (Basel). 2016 Sep 28;5(4):35. doi: 10.3390/antibiotics5040035.
Ref 3 Crystal structures of penicillin-binding protein 2 from penicillin-susceptible and -resistant strains of Neisseria gonorrhoeae reveal an unexpectedly subtle mechanism for antibiotic resistance. J Biol Chem. 2009 Jan 9;284(2):1202-12. doi: 10.1074/jbc.M805761200. Epub 2008 Nov 4.
Ref 4 In Vitro selection of Neisseria gonorrhoeae mutants with elevated MIC values and increased resistance to cephalosporins. Antimicrob Agents Chemother. 2014 Nov;58(11):6986-9. doi: 10.1128/AAC.03082-14. Epub 2014 Sep 8.
Ref 5 Effect of Variants of Penicillin-Binding Protein 2 on Cephalosporin and Carbapenem Susceptibilities in Neisseria gonorrhoeae. Antimicrob Agents Chemother. 2015 Aug;59(8):5003-6. doi: 10.1128/AAC.05143-14. Epub 2015 May 18.
Ref 6 Novel Genes Related to Ceftriaxone Resistance Found among Ceftriaxone-Resistant Neisseria gonorrhoeae Strains Selected In Vitro. Antimicrob Agents Chemother. 2016 Mar 25;60(4):2043-51. doi: 10.1128/AAC.00149-15. Print 2016 Apr.

If you find any error in data or bug in web service, please kindly report it to Dr. Sun and Dr. Yu.