Lymecycline

Identification

Name
Lymecycline
Accession Number
DB00256
Description

Lymecycline is a broad-spectrum second-generation tetracycline antibiotic used for the treatment of acne and other susceptible bacterial infections.8,9 It has been proven a cost-effective alternative to treatment with minocycline with comparable safety and efficacy.2 Lymecycline was initially discovered in 1961. It is marketed by Galderma and used in the UK as well as New Zealand in addition to other countries. Lymecycline is not marketed in the USA, however, equivalent drugs are available, such as minocycline and tetracycline.5,8

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 602.6328
Monoisotopic: 602.258793456
Chemical Formula
C29H38N4O10
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
  • Lymecycline
  • 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

Pharmacology

Pharmacology
Accelerate your drug discovery research with the industry’s only fully connected ADMET dataset, ideal for:
Machine Learning
Data Science
Drug Discovery
Accelerate your drug discovery research with our fully connected ADMET dataset
Learn more
Indication

Lymecycline is used for the treatment of acne in addition to other susceptible infections; propionibacterium is often the cause of acne.8 Some of the infections that can be treated with lymecycline include upper respiratory tract infections, urinary tract infections, bronchitis, chlamydial infections, and rickettsial infections.9

Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
Contraindications & Blackbox Warnings
With our commercial data, access important information on dangerous risks, contraindications, and adverse effects.
Learn more
Our Blackbox Warnings cover Risks, Contraindications, and Adverse Effects
Learn more
Pharmacodynamics

Lymecycline, like other tetracyclines, exerts bacteriostatic actions on intracellular and extracellular bacteria, treating susceptible bacterial infections.9 It has been shown to be safe and effective in the treatment of moderate to severe acne.1

It is important to note that like other tetracyclines, lymecycline may cause esophageal irritation and ulceration, which can be prevented by drinking adequate fluids during administration. It also has the potential to cause photosensitivity. Lymecycline can lead to renal tubular acidosis or hepatic toxicity. It is not recommended to administer this drug in patients with renal disease or severe hepatic disease.8,9

Mechanism of action

Normally, the ribosome synthesizes proteins through the binding of aminoacyl-tRNA to the mRNA-ribosome complex. Lymecycline binds to the 30S ribosomal subunit, preventing amino-acyl tRNA from binding to the A site of the ribosome, which prevents the elongation of polypeptide chains.5,6,8 This results in bacteriostatic actions, treating various infections.

TargetActionsOrganism
A30S ribosomal protein S4
inhibitor
Escherichia coli (strain K12)
Absorption

Lymecycline is 77-88% absorbed after oral administration with a relative bioavailability of 70%.4 The Cmax of lymecycline is 2.1 mg/L and is achieved about 3 hours after administration.3 The AUC is 21.9 ± 4.3 mg·h/L.3

Volume of distribution

Lymecycline is lipophilic and easily crosses the cell membrane and passively diffuses through bacterial porin channels.3,5 As a second-generation tetracycline, the concentration in the bile ranges from 10 to 25 times higher than plasma concentration.3,7 In general, the volume of distribution of tetracyclines ranges from 1.3–1.7 L/kg or 100–130 L.3

Protein binding
Not Available
Metabolism
Not Available
Route of elimination

Lymecycline is 25% eliminated in the urine.3 Based on being a member of the tetracycline drug class, fecal elimination is likely another route of elimination.7

Half-life

The half-life of lymecycline is approximately 8 hours.3

Clearance

Lymecycline is partially cleared by the kidneys, like other tetracyclines.7

Adverse Effects
Medicalerrors
Reduce medical errors
and improve treatment outcomes with our comprehensive & structured data on drug adverse effects.
Learn more
Reduce medical errors & improve treatment outcomes with our adverse effects data
Learn more
Toxicity

The oral LD50 of lymecycline in rats is 3200 mg/kg.10 Overdoses with lymecycline are rare. In the case of an overdose, gastric lavage should be performed immediately. Provide supportive treatment and maintain fluid balance.9

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

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AcenocoumarolThe risk or severity of bleeding can be increased when Lymecycline is combined with Acenocoumarol.
AcitretinThe risk or severity of pseudotumor cerebri can be increased when Acitretin is combined with Lymecycline.
AlitretinoinThe risk or severity of pseudotumor cerebri can be increased when Alitretinoin is combined with Lymecycline.
AlmasilateAlmasilate can cause a decrease in the absorption of Lymecycline resulting in a reduced serum concentration and potentially a decrease in efficacy.
AluminiumAluminium can cause a decrease in the absorption of Lymecycline resulting in a reduced serum concentration and potentially a decrease in efficacy.
Aluminium phosphateAluminium phosphate can cause a decrease in the absorption of Lymecycline resulting in a reduced serum concentration and potentially a decrease in efficacy.
Aluminum hydroxideAluminum hydroxide can cause a decrease in the absorption of Lymecycline resulting in a reduced serum concentration and potentially a decrease in efficacy.
AmobarbitalThe metabolism of Lymecycline can be increased when combined with Amobarbital.
AmoxicillinThe therapeutic efficacy of Amoxicillin can be decreased when used in combination with Lymecycline.
AmpicillinThe therapeutic efficacy of Ampicillin can be decreased when used in combination with Lymecycline.
Interactions
Improve patient outcomes
Build effective decision support tools with the industry’s most comprehensive drug-drug interaction checker.
Learn more
Food Interactions
  • Take with or without food.

Products

Products
Comprehensive & structured drug product info
From application numbers to product codes, connect different identifiers through our commercial datasets.
Learn more
Easily connect various identifiers back to our datasets
Learn more
International/Other Brands
Eficiclina / Tetralisal / Tetralysal

Categories

ATC Codes
J01AA04 — LymecyclineJ01AA20 — Combinations of tetracyclines
Drug Categories
Chemical TaxonomyProvided by Classyfire
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
1-hydroxy-2-unsubstituted benzenoid / 1-hydroxy-4-unsubstituted benzenoid / Alcohol / Alpha-amino acid / Alpha-amino acid or derivatives / Amine / Amino acid / Amino acid or derivatives / Amino fatty acid / Anthracene carboxylic acid or derivatives
show 37 more
Molecular Framework
Aromatic homopolycyclic compounds
External Descriptors
tetracyclines (CHEBI:59040)

Chemical Identifiers

UNII
7D6EM3S13P
CAS number
992-21-2
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][C@@]12C[C@@]3([H])C(C(=O)C4=C(O)C=CC=C4[C@@]3(C)O)=C(O)[C@]1(O)C(=O)C(C(=O)NCNCCCC[C@H](N)C(O)=O)=C(O)[C@H]2N(C)C

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. Dubertret L, Alirezai M, Rostain G, Lahfa M, Forsea D, Niculae BD, Simola M, Horvath A, Mizzi F: The use of lymecycline in the treatment of moderate to severe acne vulgaris: a comparison of the efficacy and safety of two dosing regimens. Eur J Dermatol. 2003 Jan-Feb;13(1):44-8. [PubMed:12609781]
  2. Bossuyt L, Bosschaert J, Richert B, Cromphaut P, Mitchell T, Al Abadie M, Henry I, Bewley A, Poyner T, Mann N, Czernielewski J: Lymecycline in the treatment of acne: an efficacious, safe and cost-effective alternative to minocycline. Eur J Dermatol. 2003 Mar-Apr;13(2):130-5. [PubMed:12695127]
  3. Agwuh KN, MacGowan A: Pharmacokinetics and pharmacodynamics of the tetracyclines including glycylcyclines. J Antimicrob Chemother. 2006 Aug;58(2):256-65. Epub 2006 Jul 1. [PubMed:16816396]
  4. Sjolin-Forsberg G, Hermansson J: Comparative bioavailability of tetracycline and lymecycline. Br J Clin Pharmacol. 1984 Oct;18(4):529-33. doi: 10.1111/j.1365-2125.1984.tb02500.x. [PubMed:6487493]
  5. Chopra I, Roberts M: Tetracycline antibiotics: mode of action, applications, molecular biology, and epidemiology of bacterial resistance. Microbiol Mol Biol Rev. 2001 Jun;65(2):232-60 ; second page, table of contents. [PubMed:11381101]
  6. Chukwudi CU: rRNA Binding Sites and the Molecular Mechanism of Action of the Tetracyclines. Antimicrob Agents Chemother. 2016 Jul 22;60(8):4433-41. doi: 10.1128/AAC.00594-16. Print 2016 Aug. [PubMed:27246781]
  7. Vojtova V, Urbanek K: [Pharmacokinetics of tetracyclines and glycylcyclines]. Klin Mikrobiol Infekc Lek. 2009 Feb;15(1):17-21. [PubMed:19399726]
  8. EMC: Tetralysal 300mg Hard Capsules [Link]
  9. New Zealand data sheet: Tetralysal (lymecycline) oral capsules [Link]
  10. ClearSynth: Lymecycline MSDS [Link]
Human Metabolome Database
HMDB0014401
KEGG Drug
D06884
PubChem Compound
54707177
PubChem Substance
46505518
ChemSpider
20121315
RxNav
6513
ChEBI
59040
ChEMBL
CHEMBL2103929
ZINC
ZINC000053682936
Therapeutic Targets Database
DAP000881
PharmGKB
PA164747190
Wikipedia
Lymecycline

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Unknown StatusTreatmentCervicitis / Chlamydia Trachomatis / Genital Mycoplasma Infection / Urethritis1
4Unknown StatusTreatmentMild to Moderate Acne1
3CompletedTreatmentAcne Vulgaris1

Pharmacoeconomics

Manufacturers
  • Lederle laboratories div american cyanamid co
Packagers
  • Galderma Laboratories
  • Proter SPA
Dosage Forms
FormRouteStrength
CapsuleOral300 mg
CapsuleOral408 MG
CapsuleOral150 MG
InjectionIntramuscular100 MG
Capsule, coatedOral300 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)192.5https://m.chemicalbook.com/ProductChemicalPropertiesCB2891297_EN.htm
boiling point (°C)928.1±65.0 http://www.chemspider.com/Chemical-Structure.20121315.html
logP-1.70http://www.chemspider.com/Chemical-Structure.20121315.html
pKa2.50±0.24https://m.chemicalbook.com/ProductChemicalPropertiesCB2891297_EN.htm
Predicted Properties
PropertyValueSource
Water Solubility1.31 mg/mLALOGPS
logP-0.27ALOGPS
logP-7.1ChemAxon
logS-2.7ALOGPS
pKa (Strongest Acidic)2.51ChemAxon
pKa (Strongest Basic)9.77ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count13ChemAxon
Hydrogen Donor Count9ChemAxon
Polar Surface Area242.98 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity154.51 m3·mol-1ChemAxon
Polarizability62.48 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

Targets

Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Yes
Actions
Inhibitor
Curator comments
A representative organism has been selected for this target. Lymecycline inhibits the 30S ribosomal subunit of various bacteria.
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. Chopra I, Roberts M: Tetracycline antibiotics: mode of action, applications, molecular biology, and epidemiology of bacterial resistance. Microbiol Mol Biol Rev. 2001 Jun;65(2):232-60 ; second page, table of contents. [PubMed:11381101]
  2. Chukwudi CU: rRNA Binding Sites and the Molecular Mechanism of Action of the Tetracyclines. Antimicrob Agents Chemother. 2016 Jul 22;60(8):4433-41. doi: 10.1128/AAC.00594-16. Print 2016 Aug. [PubMed:27246781]
  3. New Zealand data sheet: Tetralysal (lymecycline) oral capsules [Link]

Drug created on June 13, 2005 13:24 / Updated on February 21, 2021 18:50