Mezlocillin - DrugBank

ID Pharmacology Interactions References Trials Economics Properties Spectra Taxonomy

Targets (3)

Targets (3)Biointeractions (3)

Identification

Name

Mezlocillin

Accession Number

DB00948 (APRD01113)

Type

Small Molecule

Groups

Approved

Description

Semisynthetic ampicillin-derived acylureido penicillin. It has been proposed for infections with certain anaerobes and may be useful in inner ear, bile, and CNS infections. [PubChem]

Structure

MOL SDF 3D-SDF PDB SMILES InChI View 3D Structure

Synonyms

(2S,5R,6R)-3,3-Dimethyl-6-{[(2R)-2-({[3-(methylsulfonyl)-2-oxoimidazolidin-1-yl]carbonyl}amino)-2-phenylacetyl]amino}-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid

6beta-{(2R)-2-[3-(methanesulfonyl)-2-oxoimidazolidine-1-carboxamido]-2-phenylacetamido}penicillanic acid

Mezlin

Mezlocilina

Mezlocillin

Mezlocilline

Mezlocillinum

External IDs

BAY-F-1353

Product Ingredients

Ingredient	UNII	CAS	InChI Key	Details
Mezlocillin sodium	RX227TP94U	42057-22-7	GTGQRSIMEUWHPA-ZBJAFUORSA-M	Details
Mezlocillin sodium monohydrate	3CWW8B5904	80495-46-1	CZXDIDROKIDGNE-SYNJJEHYSA-M	Details

Approved Prescription Products

Not Available

Approved Generic Prescription Products

Not Available

Approved Over the Counter Products

Not Available

Unapproved/Other Products

Not Available

International Brands

Name	Company
Mezlin	Not Available

Brand mixtures

Not Available

Categories

UNII

OH2O403D1G

CAS number

51481-65-3

Weight

Average: 539.582
Monoisotopic: 539.114454181

Chemical Formula

C₂₁H₂₅N₅O₈S₂

InChI Key

YPBATNHYBCGSSN-VWPFQQQWSA-N

InChI

InChI=1S/C21H25N5O8S2/c1-21(2)14(18(29)30)26-16(28)13(17(26)35-21)22-15(27)12(11-7-5-4-6-8-11)23-19(31)24-9-10-25(20(24)32)36(3,33)34/h4-8,12-14,17H,9-10H2,1-3H3,(H,22,27)(H,23,31)(H,29,30)/t12-,13-,14+,17-/m1/s1

IUPAC Name

(2S,5R,6R)-6-[(2R)-2-[(3-methanesulfonyl-2-oxoimidazolidine-1-carbonyl)amino]-2-phenylacetamido]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid

SMILES

[H][C@]12SC(C)(C)[C@@H](N1C(=O)[C@H]2NC(=O)[C@H](NC(=O)N1CCN(C1=O)S(C)(=O)=O)C1=CC=CC=C1)C(O)=O

Pharmacology

Indication

Used to treat serious gram–negative infections of the lungs, urinary tract, and skin.

Structured Indications

Not Available

Pharmacodynamics

Mezlocillin is a penicillin beta-lactam antibiotic used in the treatment of bacterial infections caused by susceptible, usually gram-positive, organisms. The name "penicillin" can either refer to several variants of penicillin available, or to the group of antibiotics derived from the penicillins. Mezlocillin has in vitro activity against gram-positive and gram-negative aerobic and anaerobic bacteria. The bactericidal activity of mezlocillin results from the inhibition of cell wall synthesis and is mediated through mezlocillin binding to penicillin binding proteins (PBPs). Mezlocillin is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, and cephalosporinases and extended spectrum beta-lactamases. Mezlocillin can be used to treat susceptible strains of H. influenzae, Klebsiella species, Pseudomonas species, Proteus mirabilis, E. coli, Enterobacter species, Streptococcus faecelis, Peptococcus species, Peptostreptococcus species, Bacteriodes species (including B. fragilis), Morganella morganii, Serratia species, N. gonorrhoeae, P. vulgaris, and Providencia rettgeri. This drug is discontinued in the U.S.

Mechanism of action

By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, mezlocillin inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that mezlocillin interferes with an autolysin inhibitor.

Target	Kind	Pharmacological action	Actions	Organism	UniProt ID
Penicillin-binding protein 1A	Protein	yes	inhibitor	Clostridium perfringens (strain 13 / Type A)	Q8XJ01	details
Penicillin-binding protein 3	Protein	yes	inhibitor	Streptococcus pneumoniae	Q75Y35	details
Penicillin-binding protein 2	Protein	unknown	inhibitor	Escherichia coli (strain K12)	P0AD65	details

Absorption

Not Available

Volume of distribution

Not Available

Protein binding

16-59%

Metabolism

Unlike many other penicillins, mezlocillin is either extensively metabolized or is subject to biliary excretion, as only about 50% of the dose was accounted for in normal urine.

Route of elimination

Not Available

Half life

1.3 to 4.4 hours

Clearance

Not Available

Toxicity

Symptoms of overdose include rash, fever, chills, and peeling skin.

Affected organisms

Enteric bacteria and other eubacteria

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

Drug	Interaction	Drug group
Acenocoumarol	Mezlocillin may increase the anticoagulant activities of Acenocoumarol.	Approved
Aclarubicin	The serum concentration of Aclarubicin can be decreased when it is combined with Mezlocillin.	Investigational
Amikacin	The serum concentration of Amikacin can be decreased when it is combined with Mezlocillin.	Approved, Vet Approved
Amrubicin	The serum concentration of Amrubicin can be decreased when it is combined with Mezlocillin.	Approved, Investigational
Apramycin	The serum concentration of Apramycin can be decreased when it is combined with Mezlocillin.	Experimental, Vet Approved
Arbekacin	The serum concentration of Arbekacin can be decreased when it is combined with Mezlocillin.	Approved
BCG vaccine	The therapeutic efficacy of Bcg can be decreased when used in combination with Mezlocillin.	Investigational
Chlortetracycline	The therapeutic efficacy of Mezlocillin can be decreased when used in combination with Chlortetracycline.	Approved, Vet Approved
Daunorubicin	The serum concentration of Daunorubicin can be decreased when it is combined with Mezlocillin.	Approved
Demeclocycline	The therapeutic efficacy of Mezlocillin can be decreased when used in combination with Demeclocycline.	Approved
Dicoumarol	Mezlocillin may increase the anticoagulant activities of Dicoumarol.	Approved
Doxorubicin	The serum concentration of Doxorubicin can be decreased when it is combined with Mezlocillin.	Approved, Investigational
Doxycycline	The therapeutic efficacy of Mezlocillin can be decreased when used in combination with Doxycycline.	Approved, Investigational, Vet Approved
Epirubicin	The serum concentration of Epirubicin can be decreased when it is combined with Mezlocillin.	Approved
Ethyl biscoumacetate	Mezlocillin may increase the anticoagulant activities of Ethyl biscoumacetate.	Withdrawn
Fluindione	Mezlocillin may increase the anticoagulant activities of Fluindione.	Investigational
Framycetin	The serum concentration of Framycetin can be decreased when it is combined with Mezlocillin.	Approved
Geneticin	The serum concentration of Geneticin can be decreased when it is combined with Mezlocillin.	Experimental
Gentamicin	The serum concentration of Gentamicin can be decreased when it is combined with Mezlocillin.	Approved, Vet Approved
GENTAMICIN C1A	The serum concentration of GENTAMICIN C1A can be decreased when it is combined with Mezlocillin.	Experimental
Idarubicin	The serum concentration of Idarubicin can be decreased when it is combined with Mezlocillin.	Approved
Kanamycin	The serum concentration of Kanamycin can be decreased when it is combined with Mezlocillin.	Approved, Vet Approved
Methotrexate	The serum concentration of Methotrexate can be increased when it is combined with Mezlocillin.	Approved
Metrizamide	The serum concentration of Metrizamide can be decreased when it is combined with Mezlocillin.	Approved
Minocycline	The therapeutic efficacy of Mezlocillin can be decreased when used in combination with Minocycline.	Approved, Investigational
Mycophenolic acid	The serum concentration of the active metabolites of Mycophenolic acid can be reduced when Mycophenolic acid is used in combination with Mezlocillin resulting in a loss in efficacy.	Approved
Neamine	The serum concentration of Neamine can be decreased when it is combined with Mezlocillin.	Experimental
Neomycin	The serum concentration of Neomycin can be decreased when it is combined with Mezlocillin.	Approved, Vet Approved
Netilmicin	The serum concentration of Netilmicin can be decreased when it is combined with Mezlocillin.	Approved
Oxytetracycline	The therapeutic efficacy of Mezlocillin can be decreased when used in combination with Oxytetracycline.	Approved, Vet Approved
Paromomycin	The serum concentration of Paromomycin can be decreased when it is combined with Mezlocillin.	Approved, Investigational
Phenindione	Mezlocillin may increase the anticoagulant activities of Phenindione.	Approved
Phenprocoumon	Mezlocillin may increase the anticoagulant activities of Phenprocoumon.	Approved
Picosulfuric acid	The therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Mezlocillin.	Approved
Pirarubicin	The serum concentration of Pirarubicin can be decreased when it is combined with Mezlocillin.	Investigational
Plicamycin	The serum concentration of Plicamycin can be decreased when it is combined with Mezlocillin.	Approved, Withdrawn
Probenecid	The serum concentration of Mezlocillin can be increased when it is combined with Probenecid.	Approved
Puromycin	The serum concentration of Puromycin can be decreased when it is combined with Mezlocillin.	Experimental
Ribostamycin	The serum concentration of Ribostamycin can be decreased when it is combined with Mezlocillin.	Approved
Sisomicin	The serum concentration of Sisomicin can be decreased when it is combined with Mezlocillin.	Investigational
SP1049C	The serum concentration of SP1049C can be decreased when it is combined with Mezlocillin.	Investigational
Spectinomycin	The serum concentration of Spectinomycin can be decreased when it is combined with Mezlocillin.	Approved, Vet Approved
Streptomycin	The serum concentration of Streptomycin can be decreased when it is combined with Mezlocillin.	Approved, Vet Approved
Streptozocin	The serum concentration of Streptozocin can be decreased when it is combined with Mezlocillin.	Approved
Tetracycline	The therapeutic efficacy of Mezlocillin can be decreased when used in combination with Tetracycline.	Approved, Vet Approved
Tobramycin	The serum concentration of Tobramycin can be decreased when it is combined with Mezlocillin.	Approved, Investigational
Valrubicin	The serum concentration of Valrubicin can be decreased when it is combined with Mezlocillin.	Approved
Warfarin	Mezlocillin may increase the anticoagulant activities of Warfarin.	Approved
Zorubicin	The serum concentration of Zorubicin can be decreased when it is combined with Mezlocillin.	Experimental

Food Interactions

Not Available

References

Synthesis Reference

Not Available

General References

Kristof RA, Clusmann H, Koehler W, Fink KB, Schramm J: Treatment of accidental high dose intraventricular mezlocillin application by cerebrospinal fluid exchange. J Neurol Neurosurg Psychiatry. 1998 Mar;64(3):379-81. [PubMed:9527154 ]
McCormick PA, Greenslade L, Kibbler CC, Chin JK, Burroughs AK, McIntyre N: A prospective randomized trial of ceftazidime versus netilmicin plus mezlocillin in the empirical therapy of presumed sepsis in cirrhotic patients. Hepatology. 1997 Apr;25(4):833-6. [PubMed:9096584 ]
Rohde B, Werner U, Hickstein H, Ehmcke H, Drewelow B: Pharmacokinetics of mezlocillin and sulbactam under continuous veno-venous hemodialysis (CVVHD) in intensive care patients with acute renal failure. Eur J Clin Pharmacol. 1997;53(2):111-5. [PubMed:9403281 ]

External Links

Resource	Link
Human Metabolome Database (HMDB)	HMDB15083
KEGG Drug	D05021
KEGG Compound	C07221
PubChem Compound	656511
PubChem Substance	46506692
ChemSpider	570894
ChEBI	6919
ChEMBL	CHEMBL1731
Therapeutic Targets Database	DAP001180
PharmGKB	PA164750540
Wikipedia	Mezlocillin

ATC Codes

J01CR50 — Combinations of penicillins

J01CA10 — Mezlocillin

AHFS Codes

Not Available

PDB Entries

Not Available

FDA label

Not Available

MSDS

Not Available

Clinical Trials

Phase	Status	Purpose	Conditions	Count
0	Recruiting	Treatment	Osteomyelitis	1

Pharmacoeconomics

Manufacturers

Bayer pharmaceuticals corp

Packagers

Not Available

Dosage forms

Not Available

Prices

Not Available

Patents

Not Available

Properties

State

Solid

Experimental Properties

Property	Value	Source
logP	0	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.471 mg/mL	ALOGPS
logP	0.21	ALOGPS
logP	-0.84	ChemAxon
logS	-3.1	ALOGPS
pKa (Strongest Acidic)	3.49	ChemAxon
pKa (Strongest Basic)	-5.9	ChemAxon
Physiological Charge	-1	ChemAxon
Hydrogen Acceptor Count	8	ChemAxon
Hydrogen Donor Count	3	ChemAxon
Polar Surface Area	173.5 Å²	ChemAxon
Rotatable Bond Count	5	ChemAxon
Refractivity	124.88 m³·mol^-1	ChemAxon
Polarizability	51.5 Å³	ChemAxon
Number of Rings	4	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	No	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Predicted ADMET features

Property	Value	Probability
Human Intestinal Absorption	-	0.8903
Blood Brain Barrier	-	0.9802
Caco-2 permeable	-	0.6285
P-glycoprotein substrate	Substrate	0.7696
P-glycoprotein inhibitor I	Non-inhibitor	0.817
P-glycoprotein inhibitor II	Non-inhibitor	0.9892
Renal organic cation transporter	Non-inhibitor	0.8761
CYP450 2C9 substrate	Non-substrate	0.5979
CYP450 2D6 substrate	Non-substrate	0.7973
CYP450 3A4 substrate	Non-substrate	0.5132
CYP450 1A2 substrate	Non-inhibitor	0.8033
CYP450 2C9 inhibitor	Non-inhibitor	0.7397
CYP450 2D6 inhibitor	Non-inhibitor	0.8934
CYP450 2C19 inhibitor	Non-inhibitor	0.7272
CYP450 3A4 inhibitor	Non-inhibitor	0.7478
CYP450 inhibitory promiscuity	Low CYP Inhibitory Promiscuity	0.9747
Ames test	Non AMES toxic	0.6484
Carcinogenicity	Non-carcinogens	0.8275
Biodegradation	Ready biodegradable	0.8269
Rat acute toxicity	2.5003 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.9907
hERG inhibition (predictor II)	Non-inhibitor	0.7489

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum Type	Description	Splash Key
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	Not Available

Taxonomy

Description

This compound belongs to the class of chemical entities known as peptides. These are compounds containing an amide derived from two or more amino carboxylic acid molecules (the same or different) by formation of a covalent bond from the carbonyl carbon of one to the nitrogen atom of another.

Kingdom

Chemical entities

Super Class

Organic compounds

Class

Organic acids and derivatives

Sub Class

Carboxylic acids and derivatives

Direct Parent

Peptides

Alternative Parents

Penicillins / N-carbamoyl-alpha amino acids and derivatives / N-acyl-alpha amino acids and derivatives / Alpha amino acid amides / Phenylacetamides / Sulfonylureas / Imidazolidinones / Thiazolidines / Tertiary carboxylic acid amides / Sulfonyls

Substituents

Alpha peptide / Penicillin / N-acyl-alpha amino acid or derivatives / N-carbamoyl-alpha-amino acid or derivatives / Alpha-amino acid amide / N-substituted-alpha-amino acid / Alpha-amino acid or derivatives / Phenylacetamide / Penam / Sulfonylurea

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

penicillin (CHEBI:6919 )

Targets

Details

1. Penicillin-binding protein 1A

Kind: Protein
Organism: Clostridium perfringens (strain 13 / Type A)
Pharmacological action: yes
Actions: inhibitor

General Function:: Transferase activity, transferring glycosyl groups
Specific Function:: Cell wall formation. Synthesis of cross-linked peptidoglycan from the lipid intermediates. The enzyme has a penicillin-insensitive transglycosylase N-terminal domain (formation of linear glycan strands) and a penicillin-sensitive transpeptidase C-terminal domain (cross-linking of the peptide subunits) (By similarity).
Gene Name:: pbpA
Uniprot ID:: Q8XJ01
Molecular Weight:: 75176.35 Da

References

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
Lei Y, Li JT: [Affinity of penicillin-binding proteins of Escherichia coli K-12 for furbenicillin and other beta-lactam antibiotics]. Zhongguo Yao Li Xue Bao. 1989 Mar;10(2):177-80. [PubMed:2683579 ]

Details

2. Penicillin-binding protein 3

Kind: Protein
Organism: Streptococcus pneumoniae
Pharmacological action: yes
Actions: inhibitor

General Function:: Serine-type d-ala-d-ala carboxypeptidase activity
Specific Function:: Not Available
Gene Name:: pbp3
Uniprot ID:: Q75Y35
Molecular Weight:: 45209.84 Da

References

Lei Y, Li JT: [Affinity of penicillin-binding proteins of Escherichia coli K-12 for furbenicillin and other beta-lactam antibiotics]. Zhongguo Yao Li Xue Bao. 1989 Mar;10(2):177-80. [PubMed:2683579 ]
Drugeon HB, Caillon J, Moinard D, Juvin ME, Pirault JL: [Bactericidal effect of piperacillin alone and combined]. Presse Med. 1986 Dec 20;15(46):2297-302. [PubMed:2949271 ]
McCloskey RV, LeFrock JL, Smith BR, Aronoff GR: Microbiology, pharmacology, and clinical use of mezlocillin sodium. Pharmacotherapy. 1982 Nov-Dec;2(6):300-12. [PubMed:6220263 ]

Details

3. Penicillin-binding protein 2

Kind: Protein
Organism: Escherichia coli (strain K12)
Pharmacological action: unknown
Actions: inhibitor

General Function:: Serine-type d-ala-d-ala carboxypeptidase activity
Specific Function:: Cell wall formation; PBP-2 is responsible for the determination of the rod shape of the cell. It synthesizes cross-linked peptidoglycan from lipid intermediates.
Gene Name:: mrdA
Uniprot ID:: P0AD65
Molecular Weight:: 70856.1 Da

References

Lei Y, Li JT: [Affinity of penicillin-binding proteins of Escherichia coli K-12 for furbenicillin and other beta-lactam antibiotics]. Zhongguo Yao Li Xue Bao. 1989 Mar;10(2):177-80. [PubMed:2683579 ]

Drug created on June 13, 2005 07:24 / Updated on July 18, 2017 16:54

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Structure for DB00948 (Mezlocillin)

Targets

References

References

References