Amdinocillin - DrugBank

ID Pharmacology Interactions References Trials Economics Properties Spectra Taxonomy

Targets (6)

Targets (6)Biointeractions (6)

Identification

Name

Amdinocillin

Accession Number

DB01163 (APRD00789)

Type

Small Molecule

Groups

Withdrawn

Description

Amidinopenicillanic acid derivative with broad spectrum antibacterial action. It is poorly absorbed if given orally and is used in urinary infections and typhus. Amdinocillin is not available in the United States.

Structure

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

Synonyms

Mecillinam

Penicillin HX

External IDs

Not Available

Product Ingredients

Not Available

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
Coactin	Not Available
Selexid	Leo

Brand mixtures

Not Available

Categories

UNII

V10579P3QZ

CAS number

32887-01-7

Weight

Average: 325.426
Monoisotopic: 325.146012307

Chemical Formula

C₁₅H₂₃N₃O₃S

InChI Key

BWWVAEOLVKTZFQ-ISVUSNJMSA-N

InChI

InChI=1S/C15H23N3O3S/c1-15(2)11(14(20)21)18-12(19)10(13(18)22-15)16-9-17-7-5-3-4-6-8-17/h9-11,13H,3-8H2,1-2H3,(H,20,21)/b16-9+/t10-,11+,13-/m1/s1

IUPAC Name

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

SMILES

[H]C(=N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@]12[H])N1CCCCCC1

Pharmacology

Indication

Used in the treatment of urinary tract infections caused by some strains of E. coli and klebsiella and enterobacter species. Used mainly against Gram negative organisms.

Structured Indications

Not Available

Pharmacodynamics

Amdinocillin is a novel, semisynthetic penicillin effective against many gram-negative bacteria. The antibacterial activity of amdinocillin is derived from its ability to bind specifically and avidly to Penicillin Binding Protein-2 (PBP 2). Amdinocillin is active alone against many gram-negative organisms. Pseudomonas and non-fermenting gram-negative bacteria, however, are usually resistant. Amdinocillin, in combination with many beta-lactams, exhibits marked synergy against many enterobacteriaceae. No such synergy can be demonstrated for gram-positive organisms or pseudomonas species. Amdinocillin is not beta-lactamase stable. Organisms which produce high levels of plasma-mediated beta-lactamase are resistant to the drug. Co-administration of probenecid results in markedly elevated plasma levels of amdinocillin and delays its excretion.

Mechanism of action

Amdinocillin is a stong and specific antagonist of Penicillin Binding Protein-2 (PBP 2). It is active against gram negative bacteria, preventing cell wall synthesis by inhibiting the activity of PBP2. PBP2 is a peptidoglycan elongation initiating enzyme. Peptidoglycan is a polymer of sugars and amino acids that is the main component of bacterial cell walls.

Target	Kind	Pharmacological action	Actions	Organism	UniProt ID
Penicillin-binding protein 2a	Protein	yes	inhibitor	Streptococcus pneumoniae (strain ATCC BAA-255 / R6)	Q8DNB6	details
Penicillin-binding protein 2	Protein	yes	inhibitor	Escherichia coli (strain K12)	P0AD65	details
Penicillin-binding protein 3	Protein	yes	inhibitor	Streptococcus pneumoniae	Q75Y35	details
Penicillin-binding protein 1A	Protein	yes	inhibitor	Streptococcus pneumoniae (strain ATCC BAA-255 / R6)	Q8DR59	details
Penicillin-binding protein 2B	Protein	yes	inhibitor	Streptococcus pneumoniae (strain ATCC BAA-255 / R6)	P0A3M6	details
Penicillin-binding protein 1b	Protein	yes	inhibitor	Streptococcus pneumoniae (strain ATCC BAA-255 / R6)	Q7CRA4	details

Absorption

Poorly absorbed if given orally.

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

Not Available

Route of elimination

Not Available

Half life

Approximately 1 hour in patients with normal renal function. Increases to 3 to 6 hours in anephric patients.

Clearance

Not Available

Toxicity

Not Available

Affected organisms

Gram-negative Bacteria
Staphylococcus saprophyticus
Escherichia coli
Proteus mirabilis

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

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

Food Interactions

Not Available

References

Synthesis Reference

U.S. Patent 3,957,764.

General References

Neu HC: Penicillin-binding proteins and role of amdinocillin in causing bacterial cell death. Am J Med. 1983 Aug 29;75(2A):9-20. [PubMed:6311012 ]

External Links

Resource	Link
KEGG Drug	D02888
PubChem Compound	36273
PubChem Substance	46508450
ChemSpider	33357
ChEBI	51208
ChEMBL	CHEMBL530
Therapeutic Targets Database	DAP001176
PharmGKB	PA164754807

ATC Codes

J01CA11 — Mecillinam

AHFS Codes

Not Available

PDB Entries

Not Available

FDA label

Not Available

MSDS

Download (42.1 KB)

Clinical Trials

Phase	Status	Purpose	Conditions	Count
1	Completed	Treatment	Acute Cystitis (Excl in Pregnancy)	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage forms

Not Available

Prices

Not Available

Patents

Not Available

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	156 dec °C	PhysProp
water solubility	0.0103 mg/mL at 25 °C	MEYLAN,WM et al. (1996)
logP	1.3	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.979 mg/mL	ALOGPS
logP	1.41	ALOGPS
logP	-0.55	ChemAxon
logS	-2.5	ALOGPS
pKa (Strongest Acidic)	3.3	ChemAxon
pKa (Strongest Basic)	7.92	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	5	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	73.21 Å²	ChemAxon
Rotatable Bond Count	2	ChemAxon
Refractivity	84.31 m³·mol^-1	ChemAxon
Polarizability	34.18 Å³	ChemAxon
Number of Rings	3	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Predicted ADMET features

Property	Value	Probability
Human Intestinal Absorption	-	0.8439
Blood Brain Barrier	-	0.9659
Caco-2 permeable	-	0.6287
P-glycoprotein substrate	Substrate	0.7402
P-glycoprotein inhibitor I	Non-inhibitor	0.6666
P-glycoprotein inhibitor II	Non-inhibitor	0.9677
Renal organic cation transporter	Non-inhibitor	0.7438
CYP450 2C9 substrate	Non-substrate	0.7291
CYP450 2D6 substrate	Non-substrate	0.779
CYP450 3A4 substrate	Substrate	0.5355
CYP450 1A2 substrate	Non-inhibitor	0.8467
CYP450 2C9 inhibitor	Non-inhibitor	0.8666
CYP450 2D6 inhibitor	Non-inhibitor	0.9033
CYP450 2C19 inhibitor	Non-inhibitor	0.7809
CYP450 3A4 inhibitor	Non-inhibitor	0.8914
CYP450 inhibitory promiscuity	Low CYP Inhibitory Promiscuity	0.9761
Ames test	Non AMES toxic	0.7016
Carcinogenicity	Non-carcinogens	0.8428
Biodegradation	Not ready biodegradable	0.5648
Rat acute toxicity	1.5443 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.9958
hERG inhibition (predictor II)	Non-inhibitor	0.7974

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

Spectra

Mass Spec (NIST)

Not Available

Spectra

Not Available

Taxonomy

Description

This compound belongs to the class of chemical entities known as alpha amino acids and derivatives. These are amino acids in which the amino group is attached to the carbon atom immediately adjacent to the carboxylate group (alpha carbon), or a derivative thereof.

Kingdom

Chemical entities

Super Class

Organic compounds

Class

Organic acids and derivatives

Sub Class

Carboxylic acids and derivatives

Direct Parent

Alpha amino acids and derivatives

Alternative Parents

Penams / Azepanes / Thiazolidines / Tertiary carboxylic acid amides / Azetidines / Azacyclic compounds / Thiohemiaminal derivatives / Propargyl-type 1,3-dipolar organic compounds / Carboxamidines / Monocarboxylic acids and derivatives

Substituents

Alpha-amino acid or derivatives / Penam / Azepane / Beta-lactam / Tertiary carboxylic acid amide / Thiazolidine / Azetidine / Carboxamide group / Lactam / Amidine

Molecular Framework

Aliphatic heteropolycyclic compounds

External Descriptors

penicillin (CHEBI:51208 )

Targets

Details

1. Penicillin-binding protein 2a

Kind: Protein
Organism: Streptococcus pneumoniae (strain ATCC BAA-255 / R6)
Pharmacological action: yes
Actions: inhibitor

General Function:: Transferase activity, transferring acyl groups
Specific Function:: Not Available
Gene Name:: pbp2a
Uniprot ID:: Q8DNB6
Uniprot Name:: Penicillin-binding protein 2a
Molecular Weight:: 80797.94 Da

References

Williamson R, Hakenbeck R, Tomasz A: In vivo interaction of beta-lactam antibiotics with the penicillin-binding proteins of Streptococcus pneumoniae. Antimicrob Agents Chemother. 1980 Oct;18(4):629-37. [PubMed:7447421 ]

Details

2. Penicillin-binding protein 2

Kind: Protein
Organism: Escherichia coli (strain K12)
Pharmacological action: yes
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
Uniprot Name:: Penicillin-binding protein 2
Molecular Weight:: 70856.1 Da

References

Neu HC: Penicillin-binding proteins and role of amdinocillin in causing bacterial cell death. Am J Med. 1983 Aug 29;75(2A):9-20. [PubMed:6311012 ]
Licht J, Gally D, Henderson T, Young K, Cooper S: Effect of mecillinam on peptidoglycan synthesis during the division cycle of Salmonella typhimurium 2616. Res Microbiol. 1993 Jul-Aug;144(6):423-33. [PubMed:8190989 ]

Details

3. 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
Uniprot Name:: Penicillin-binding protein 3
Molecular Weight:: 45209.84 Da

References

Williamson R, Hakenbeck R, Tomasz A: In vivo interaction of beta-lactam antibiotics with the penicillin-binding proteins of Streptococcus pneumoniae. Antimicrob Agents Chemother. 1980 Oct;18(4):629-37. [PubMed:7447421 ]

Details

4. Penicillin-binding protein 1A

Kind: Protein
Organism: Streptococcus pneumoniae (strain ATCC BAA-255 / R6)
Pharmacological action: yes
Actions: inhibitor

General Function:: Penicillin binding
Specific Function:: Cell wall formation.
Gene Name:: pbpA
Uniprot ID:: Q8DR59
Uniprot Name:: Penicillin-binding protein 1A
Molecular Weight:: 79700.9 Da

References

Williamson R, Hakenbeck R, Tomasz A: In vivo interaction of beta-lactam antibiotics with the penicillin-binding proteins of Streptococcus pneumoniae. Antimicrob Agents Chemother. 1980 Oct;18(4):629-37. [PubMed:7447421 ]

Details

5. Penicillin-binding protein 2B

Kind: Protein
Organism: Streptococcus pneumoniae (strain ATCC BAA-255 / R6)
Pharmacological action: yes
Actions: inhibitor

General Function:: Not Available
Specific Function:: Penicillin binding
Gene Name:: penA
Uniprot ID:: P0A3M6
Uniprot Name:: Penicillin-binding protein 2B
Molecular Weight:: 73872.305 Da

References

Williamson R, Hakenbeck R, Tomasz A: In vivo interaction of beta-lactam antibiotics with the penicillin-binding proteins of Streptococcus pneumoniae. Antimicrob Agents Chemother. 1980 Oct;18(4):629-37. [PubMed:7447421 ]

Details

6. Penicillin-binding protein 1b

Kind: Protein
Organism: Streptococcus pneumoniae (strain ATCC BAA-255 / R6)
Pharmacological action: yes
Actions: inhibitor

General Function:: Transferase activity, transferring acyl groups
Specific Function:: Not Available
Gene Name:: pbp1b
Uniprot ID:: Q7CRA4
Uniprot Name:: Penicillin-binding protein 1b
Molecular Weight:: 89479.92 Da

References

Williamson R, Hakenbeck R, Tomasz A: In vivo interaction of beta-lactam antibiotics with the penicillin-binding proteins of Streptococcus pneumoniae. Antimicrob Agents Chemother. 1980 Oct;18(4):629-37. [PubMed:7447421 ]

Drug created on June 13, 2005 07:24 / Updated on July 18, 2017 16:56

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Structure for DB01163 (Amdinocillin)

Targets

References

References

References

References

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