cefiderocol 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
antibiotics, cefalosporanic acid derivatives 5352 1225208-94-5

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • cefiderocol
  • cefiderocol sulfate tosylate
  • S-649266
  • GSK2696266
  • fetcroja
Cefiderocol is a cephalosporin antibacterial with activity against Gram-negative aerobic bacteria. Cefiderocol functions as a siderophore and binds to extracellular free ferric iron. In addition to passive diffusion via porin channels, cefiderocol is actively transported across the outer cell membrane of bacteria into the periplasmic space using a siderophore iron uptake mechanism. Cefiderocol exerts bactericidal action by inhibiting cell wall biosynthesis through binding to penicillin-binding proteins (PBPs)
  • Molecular weight: 752.21
  • Formula: C30H34ClN7O10S2
  • CLOGP: -3.98
  • LIPINSKI: 3
  • HAC: 17
  • HDO: 6
  • TPSA: 256.90
  • ALOGS: -5.60
  • ROTB: 13
  • Status: ONP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
6 g P

ADMET properties:

PropertyValueReference
S (Water solubility) 100 mg/mL Bocci G, Oprea TI, Benet LZ
BDDCS (Biopharmaceutical Drug Disposition Classification System) 3 Bocci G, Oprea TI, Benet LZ
BA (Bioavailability) 70 %

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 -1.778 Moderate 0.75
caco2-efflux Caco-2 efflux ratio (BA/AB) 0.659 Moderate 0.75
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 0.283 10^-6 cm/s Moderate 0.75
dh-clint Dog hepatocyte intrinsic clearance 1.151 uL/min/10^6 cells Moderate 0.75
dppb Dog plasma protein binding (% unbound) 75.930 % Moderate 0.75
fcs-ppb Fetal calf serum protein binding (% unbound) 65.690 % Moderate 0.75
herg hERG pIC50 4.558 pIC50 Moderate 0.75
hh-clint Human hepatocyte intrinsic clearance 3.243 uL/min/10^6 cells Moderate 0.75
hlm-clint Human liver microsomal intrinsic clearance 4.385 uL/min/mg protein Moderate 0.75
hppb Human plasma protein binding (% unbound) 64.540 % Moderate 0.75
kinase-safety-class AAK1,ACVR2A,ACVR2B,ACVRL1,AKT2,AKT3,ALK,AURKA,AURKB,AURKC,AXL,BRAF,BTK,CAMK2B,CAMK2D,CDK19,CDK2,CDK4,CDK5,CDK9,DDR1,DYRK1B,DYRK3,EGFR,EIF2AK3,EPHA2,EPHB4,ERBB2,FGFR1,FLT3,GRK2,GRK3,GSK3A,GSK3B,IKBKB,ITK,JAK1,JAK2,JAK3,KDR,KIT,MAP2K6,MAP3K1,MAP3K14,MAP3K2,MAP3K21,MAP3K3,MAP3K7,MAP4K1,MAPK1,MAPK10,MAPK12,MAPK7,MAPK8,MAPK9,MAPKAPK2,MAPKAPK5,MARK4,MELK,MTOR,NTRK2,PDK1,PDK2,PDK4,PDPK1,PIK3CA,PIK3CB,PIK3CD,PIK3CG,PIM1,PIM2,PIM3,PLK1,PRKCD,PRKDC,PTK2,SGK1,SIK2,SIK3,STK10,STK33,SYK,TEK,TGFBR1,TTK,ULK1,ULK2,ZAP70 88
kinase-selectivity-class ACVR2B,AURKC,AXL,BRAF,CDK4,CDK9,DYRK1B,EIF2AK3,EPHB4,GRK2,JAK2,MAP2K6,MAP3K14,MAPK12,MAPK7,MAPK8,MARK4,PRKDC,SIK2,STK33,SYK,TEK,TGFBR1,TTK 24
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 0.841 Moderate 0.75
mh-clint Mouse hepatocyte intrinsic clearance 5.662 Moderate 0.75
mppb Mouse plasma protein binding (% unbound) 70.100 Moderate 0.75
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 0.828 Moderate 0.75
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 60.990 % Moderate 0.75
rh-clint Rat hepatocyte intrinsic clearance 3.491 uL/min/10^6 cells Moderate 0.75
rh-fuinc Rat hepatocyte fraction unbound in incubation 87.320 % Moderate 0.75
rppb Rat plasma protein binding (% unbound) 50.290 % Moderate 0.75
solubility-dd Solubility at pH 7.4 in DMSO 914.113 uM Moderate 0.75

Approvals:

DateAgencyCompanyOrphan
April 23, 2020 EMA Shionogi B.V.
Nov. 14, 2019 FDA SHIONOGI INC

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Pathogen resistance 116.07 84.40 22 452 8093 90619880

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Drug resistance 137.84 73.38 39 507 34209 42586580
Death 116.72 73.38 72 474 471113 42149676

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Death 191.56 79.84 103 938 698766 109889492
Drug resistance 188.24 79.84 52 989 56322 110531936
Pathogen resistance 152.97 79.84 35 1006 17637 110570621
Treatment failure 107.39 79.84 52 989 277182 110311076
Drug ineffective 81.38 79.84 84 957 1520456 109067802

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC J01DI04 ANTIINFECTIVES FOR SYSTEMIC USE
ANTIBACTERIALS FOR SYSTEMIC USE
OTHER BETA-LACTAM ANTIBACTERIALS
Other cephalosporins and penems
FDA CS M0003827 Cephalosporins
FDA EPC N0000175488 Cephalosporin Antibacterial
MeSH PA D000097902 beta Lactam Antibiotics
MeSH PA D000890 Anti-Infective Agents
MeSH PA D000900 Anti-Bacterial Agents
MeSH PA D002614 Chelating Agents
MeSH PA D007502 Iron Chelating Agents
MeSH PA D017262 Siderophores
MeSH PA D064449 Sequestering Agents
CHEBI has role CHEBI:26672 siderophore
CHEBI has role CHEBI:36047 antibacterial drug
CHEBI has role CHEBI:33282 antibacterial agent
CHEBI has role CHEBI:35441 antiinfective agent

Related Drugs by ATC class:

J01DI Other cephalosporins and penems 5 drugs
ceftaroline fosamilceftobiprole medocarilceftolozanefaropenemprobenecid

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Pyelonephritis indication 45816000 DOID:11400
Urinary tract infectious disease indication 68566005
Escherichia coli urinary tract infection indication 301011002
Proteus urinary tract infection indication 301012009
Pseudomonas urinary tract infection indication 301013004
Bacterial urinary infection indication 312124009
Gram-Negative Bacterial Infections indication 371583007
Urinary tract infection caused by Klebsiella indication




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 2.35 acidic
pKa2 3.44 acidic
pKa3 6.17 acidic
pKa4 9.6 acidic
pKa5 13.61 acidic
pKa6 2.83 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
EQ 1GM BASE/VIAL FETROJA SHIONOGI N209445 Nov. 14, 2019 RX POWDER INTRAVENOUS 9238657 Nov. 14, 2033 METHOD OF TREATING BACTERIAL INFECTIONS
EQ 1GM BASE/VIAL FETROJA SHIONOGI N209445 Nov. 14, 2019 RX POWDER INTRAVENOUS 9238657 Nov. 14, 2033 METHOD OF TREATING COMPLICATED URINARY TRACT INFECTIONS (CUTI), INCLUDING PYELONEPHRITIS, COMPRISING ADMINISTERING CEFIDEROCOL SULFATE TOSYLATE
EQ 1GM BASE/VIAL FETROJA SHIONOGI N209445 Nov. 14, 2019 RX POWDER INTRAVENOUS 9238657 Nov. 14, 2033 METHOD OF TREATING HOSPITAL-ACQUIRED BACTERIAL PNEUMONIA AND VENTILATOR-ASSOCIATED BACTERIAL PNEUMONIA (HABP/VABP) COMPRISING ADMINISTERING CEFIDEROCOL SULFATE TOSYLATE

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
EQ 1GM BASE/VIAL FETROJA SHIONOGI N209445 Nov. 14, 2019 RX POWDER INTRAVENOUS Nov. 14, 2024 NEW CHEMICAL ENTITY
EQ 1GM BASE/VIAL FETROJA SHIONOGI N209445 Nov. 14, 2019 RX POWDER INTRAVENOUS Nov. 14, 2029 GENERATING ANTIBIOTIC INCENTIVES NOW

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Peptidoglycan synthase FtsI Enzyme INHIBITOR IC50 7.40 SCIENTIFIC LITERATURE DRUG LABEL
Penicillin-binding protein 1A Enzyme INHIBITOR IC50 6.07 SCIENTIFIC LITERATURE DRUG LABEL
Penicillin-binding protein 1A Enzyme INHIBITOR IC50 5.48 SCIENTIFIC LITERATURE DRUG LABEL
Penicillin-binding protein 1B Enzyme INHIBITOR IC50 5.47 SCIENTIFIC LITERATURE DRUG LABEL
Penicillin-binding protein 1A Enzyme INHIBITOR IC50 5.98 SCIENTIFIC LITERATURE DRUG LABEL
Penicillin-binding protein 1B Enzyme INHIBITOR IC50 5.46 SCIENTIFIC LITERATURE DRUG LABEL
Peptidoglycan D,D-transpeptidase MrdA Enzyme INHIBITOR IC50 5.66 SCIENTIFIC LITERATURE DRUG LABEL
Peptidoglycan D,D-transpeptidase MrdA Enzyme INHIBITOR IC50 7.20 SCIENTIFIC LITERATURE DRUG LABEL
Peptidoglycan D,D-transpeptidase FtsI Enzyme INHIBITOR IC50 7.21 SCIENTIFIC LITERATURE DRUG LABEL
Peptidoglycan D,D-transpeptidase FtsI Enzyme INHIBITOR IC50 7.22 SCIENTIFIC LITERATURE DRUG LABEL
Peptidoglycan D,D-transpeptidase FtsI Enzyme INHIBITOR IC50 6.17 SCIENTIFIC LITERATURE DRUG LABEL
Penicillin-binding protein 4 Enzyme INHIBITOR IC50 5.44 SCIENTIFIC LITERATURE DRUG LABEL

External reference:

IDSource
SZ34OMG6E8 UNII
2135543-94-9 SECONDARY_CAS_RN
4039174 VANDF
C4548369 UMLSCUI
CHEBI:140376 CHEBI
CHEMBL3989974 ChEMBL_ID
77843966 PUBCHEM_CID
DB14879 DRUGBANK_ID
CHEMBL4297211 ChEMBL_ID
D000097602 MESH_DESCRIPTOR_UI
D11302 KEGG_DRUG
10234 INN_ID
10776 IUPHAR_LIGAND_ID
1217151007 SNOMEDCT_US
830101009 SNOMEDCT_US
830161006 SNOMEDCT_US
37832 MMSL
d09462 MMSL
018219 NDDF
018220 NDDF
2265702 RXNORM

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Fetroja HUMAN PRESCRIPTION DRUG LABEL 1 59630-266 INJECTION, POWDER, FOR SOLUTION 1 g INTRAVENOUS NDA 31 sections