Identification

Name
Lymecycline
Accession Number
DB00256  (APRD00565, EXPT01049)
Type
Small Molecule
Groups
Approved, Investigational
Description

A tetracycline with a 7-chloro substitution.

Structure
Thumb
Synonyms
  • (+)-N-(5-Amino-5-carboxypentylaminomethyl)-4-dimethylamino-1,4,4a,5,5a,6,11,12a-octahydro-3,6,10,12,12a-pentahydroxy-6-methyl-1,11-dioxonaphthacene-2-carboxamide
  • Limeciclina
  • Lymecyclinum
  • N-Lysinomethyltetracycline
  • N2-(((+)-5-Amino-5-carboxypentylamino)methyl)tetracycline
  • N6-((4-(Dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,6,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-2-naphthacenecarboxamido)methyl)lysine
  • Tetracycline-L-methylene lysine
  • Tetracycline-L-methylenelysine
International/Other Brands
Eficiclina / Tetralisal / Tetralysal
Categories
UNII
7D6EM3S13P
CAS number
992-21-2
Weight
Average: 602.6328
Monoisotopic: 602.258793456
Chemical Formula
C29H38N4O10
InChI Key
AHEVKYYGXVEWNO-UEPZRUIBSA-N
InChI
InChI=1S/C29H38N4O10/c1-28(42)13-7-6-9-17(34)18(13)22(35)19-14(28)11-15-21(33(2)3)23(36)20(25(38)29(15,43)24(19)37)26(39)32-12-31-10-5-4-8-16(30)27(40)41/h6-7,9,14-16,21,31,34,36-37,42-43H,4-5,8,10-12,30H2,1-3H3,(H,32,39)(H,40,41)/t14-,15-,16-,21-,28+,29-/m0/s1
IUPAC Name
(2S)-6-[({[(4S,4aS,5aS,6S,12aS)-4-(dimethylamino)-3,6,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracen-2-yl]formamido}methyl)amino]-2-aminohexanoic acid
SMILES
[H][[email protected]@]12C[[email protected]@]3([H])C(C(=O)C4=C(O)C=CC=C4[[email protected]@]3(C)O)=C(O)[[email protected]]1(O)C(=O)C(C(=O)NCNCCCC[[email protected]](N)C(O)=O)=C(O)[[email protected]]2N(C)C

Pharmacology

Indication

For the treatment of infections and to treat acne. It may also be used to treat urinary tract infections, gum disease, and other bacterial infections such as gonorrhea and chlamydia. Lymecycline is also used commonly as a prophylactic treatment for infection by Bacillus anthracis (anthrax). It is also effective against Yersinia pestis and malaria and is also prescribed for the treatment of Lyme disease.

Structured Indications
Not Available
Pharmacodynamics

Lymecycline is a tetracycline broad-spectrum antibiotic. It is approximately 5000 times more soluble than tetracycline base and is unique amongst tetracyclines in that it is absorbed by the "active transport" process across the intestinal wall, making use of the same fast and efficient mechanism by which carbohydrates are absorbed. It inhibits cell growth by inhibiting translation.

Mechanism of action

Lymecycline inhibits cell growth by inhibiting translation. It binds to the 30S ribosomal subunit and prevents the amino-acyl tRNA from binding to the A site of the ribosome. The binding is reversible in nature. Lymecycline is lipophilic and can easily pass through the cell membrane or passively diffuses through porin channels in the bacterial membrane. Cells become resistant to lymecycline by at least two mechanisms: efflux and ribosomal protection. In efflux, a resistance gene encodes a membrane protein that actively pumps lymecycline out of the cell. This is the mechanism of action of the tetracycline resistance gene on the artificial plasmid pBR322. In ribosomal protection, a resistance gene encodes a protein which binds to the ribosome and prevents lymecycline from acting on the ribosome.

TargetActionsOrganism
U30S ribosomal protein S4
inhibitor
Escherichia coli (strain K12)
U30S ribosomal protein S9
inhibitor
Escherichia coli (strain K12)
Absorption

Absorption is fast and efficient. Bioavailability is 100% following oral administration.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

Adverse effects include nausea, vomiting, diarrhoea, glossitis, enterocolitis, dysphagia, dermatitis, hypersensitivity reactions, proctitis, and vaginitis.

Affected organisms
  • Enteric bacteria and other eubacteria
Pathways
PathwayCategory
Lymecycline Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Lymecycline.Investigational
MedrogestoneThe serum concentration of Medrogestone can be decreased when it is combined with Lymecycline.Approved
Picosulfuric acidThe therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Lymecycline.Approved
Procaine benzylpenicillinThe therapeutic efficacy of Procaine benzylpenicillin can be decreased when used in combination with Lymecycline.Approved, Vet Approved
Technetium Tc-99m oxidronateLymecycline can cause a decrease in the absorption of Technetium Tc-99m oxidronate resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
Food Interactions
  • Do not to take any indigestion remedies, iron or zinc supplements at the same time as this medicine.

References

Synthesis Reference

Willis L. Winstrom, "Process and apparatus for the preparation of chlortetracycline-containing animal feed compositions." U.S. Patent US06844006, issued January 18, 2005.

US06844006
General References
  1. Meynadier J, Alirezai M: Systemic antibiotics for acne. Dermatology. 1998;196(1):135-9. [PubMed:9557248]
External Links
Human Metabolome Database
HMDB14401
KEGG Drug
D06884
PubChem Compound
54707177
PubChem Substance
46505518
ChemSpider
20121315
ChEBI
59040
ChEMBL
CHEMBL2103929
Therapeutic Targets Database
DAP000881
PharmGKB
PA164747190
Wikipedia
Lymecycline
ATC Codes
J01AA04 — LymecyclineJ01AA20 — Combinations of tetracyclines

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Unknown StatusTreatmentCervicitis / Chlamydia Trachomatis / Genital Mycoplasma Infection / Urethritis1

Pharmacoeconomics

Manufacturers
  • Lederle laboratories div american cyanamid co
Packagers
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilitySoluble (at all physiological pH values)Not Available
logP0.3Not Available
Predicted Properties
PropertyValueSource
Water Solubility1.31 mg/mLALOGPS
logP-0.27ALOGPS
logP-8.3ChemAxon
logS-2.7ALOGPS
pKa (Strongest Acidic)0.4ChemAxon
pKa (Strongest Basic)9.5ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count13ChemAxon
Hydrogen Donor Count9ChemAxon
Polar Surface Area242.98 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity154.51 m3·mol-1ChemAxon
Polarizability62.88 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.7376
Blood Brain Barrier-0.9893
Caco-2 permeable-0.6208
P-glycoprotein substrateSubstrate0.9292
P-glycoprotein inhibitor INon-inhibitor0.9211
P-glycoprotein inhibitor IINon-inhibitor0.6582
Renal organic cation transporterNon-inhibitor0.8738
CYP450 2C9 substrateNon-substrate0.7747
CYP450 2D6 substrateNon-substrate0.8136
CYP450 3A4 substrateSubstrate0.6766
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9123
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8593
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9265
Ames testNon AMES toxic0.6718
CarcinogenicityNon-carcinogens0.9182
BiodegradationNot ready biodegradable0.8673
Rat acute toxicity2.5422 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9699
hERG inhibition (predictor II)Inhibitor0.5732
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as tetracyclines. These are polyketides having an octahydrotetracene-2-carboxamide skeleton, substituted with many hydroxy and other groups.
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Tetracyclines
Sub Class
Not Available
Direct Parent
Tetracyclines
Alternative Parents
Naphthacenes / Anthracenecarboxylic acids and derivatives / L-alpha-amino acids / Tetralins / Aryl ketones / Medium-chain fatty acids / Amino fatty acids / 1-hydroxy-4-unsubstituted benzenoids / Hydroxy fatty acids / Aralkylamines
show 16 more
Substituents
Tetracycline / Naphthacene / Tetracene / Anthracene carboxylic acid or derivatives / Tetralin / L-alpha-amino acid / Alpha-amino acid / Alpha-amino acid or derivatives / Aryl ketone / Medium-chain fatty acid
show 37 more
Molecular Framework
Aromatic homopolycyclic compounds
External Descriptors
tetracyclines (CHEBI:59040)

Targets

Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Translation repressor activity, nucleic acid binding
Specific Function
One of two assembly initiator proteins for the 30S subunit, it binds directly to 16S rRNA where it nucleates assembly of the body of the 30S subunit.With S5 and S12 plays an important role in trans...
Gene Name
rpsD
Uniprot ID
P0A7V8
Uniprot Name
30S ribosomal protein S4
Molecular Weight
23468.915 Da
References
  1. 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]
  2. 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]
  3. Smythies JR, Benington F, Morin RD: On the molecular mechanism of action of the tetracyclines. Experientia. 1972 Oct 15;28(10):1253-4. [PubMed:5087060]
Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Trna binding
Specific Function
The C-terminal tail plays a role in the affinity of the 30S P site for different tRNAs. Mutations that decrease this affinity are suppressed in the 70S ribosome.
Gene Name
rpsI
Uniprot ID
P0A7X3
Uniprot Name
30S ribosomal protein S9
Molecular Weight
14856.105 Da
References
  1. 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]
  2. 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]
  3. Smythies JR, Benington F, Morin RD: On the molecular mechanism of action of the tetracyclines. Experientia. 1972 Oct 15;28(10):1253-4. [PubMed:5087060]

Drug created on June 13, 2005 07:24 / Updated on November 07, 2017 01:35