Identification

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Name
Meclocycline
Accession Number
DB13092  (DB06798, DB05709)
Type
Small Molecule
Groups
Experimental, Investigational
Description

Meclocycline is under investigation in clinical trial NCT00385515 (Efficacy of SNX-1012 in the Treatment of Oral Mucositis) 3.

Structure
Thumb
Synonyms
Not Available
External IDs
GS-2989 / NSC-78502
Product Ingredients
IngredientUNIICASInChI Key
Meclocycline sulfosalicylate46VZA7RX2B73816-42-9FYSVKUUNXYGFLA-CCHMMTNSSA-N
Categories
UNII
23Q8M2HE6S
CAS number
2013-58-3
Weight
Average: 476.87
Monoisotopic: 476.0986433
Chemical Formula
C22H21ClN2O8
InChI Key
GGQJXCQBBONZFX-IWVLMIASSA-N
InChI
InChI=1S/C22H21ClN2O8/c1-6-9-7(23)4-5-8(26)11(9)16(27)12-10(6)17(28)14-15(25(2)3)18(29)13(21(24)32)20(31)22(14,33)19(12)30/h4-5,10,14-15,17,26,28-30,33H,1H2,2-3H3,(H2,24,32)/t10-,14-,15+,17+,22+/m1/s1
IUPAC Name
(4S,4aR,5S,5aR,12aS)-7-chloro-4-(dimethylamino)-3,5,10,12,12a-pentahydroxy-6-methylidene-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide
SMILES
CN(C)[C@H]1[C@@H]2[C@@H](O)[C@@H]3C(=C)C4=C(Cl)C=CC(O)=C4C(=O)C3=C(O)[C@]2(O)C(=O)C(C(N)=O)=C1O

Pharmacology

Indication

Currently under investigation for the topical treatment of ulcerative oral mucositis 3

Pharmacodynamics

Tetracyclines such as meclocycline are broad spectrum bacteriostatic agents 1. Meclocyclin likely inhibits the growth of bacterial species present in the damaged oral mucosa, allowing the immune system to more easily eliminate infections.

Mechanism of action

As a tetracycline, meclocycline likely works by reversably associating with the 30s subint of the bacterial ribosome 1. A likely binding site for tetracyclines has been identified on protein S7 of this subunit. This association blocks the association of aminoacyl-tRNA with the ribosome, inhibiting protein synthesis. Ultimately this inhibits bacterial growth due to a lack of proteins necessary for reproduction.

TargetActionsOrganism
A30S ribosomal protein S7
antagonist
Escherichia coli (strain K12)
Absorption

Estimated oral bioavailability of ~66% and tmax of 4h based on that of demeclocycline due to structural similarity 2.

Volume of distribution

Estimated Vd of 121L based on that of demeclocycline due to structural similarity 2.

Protein binding

Estimated plasma protein binding of ~75-91% based on that of demeclocycline due to structural similarity 2.

Metabolism

Most tetracyclines are not metabolized. It is unlikely that meclocycline would be metabolized 2.

Route of elimination

Estimated urinary excretion of ~40% and fecal excretion of ~43% based on that of demeclocycline due to structural similarity 2.

Half life

Half life estimated to be ~5.6h based on that of chlortetracycline due to structural similarity 2.

Clearance
Not Available
Toxicity

Oral LD50 of 6443mg/kg in rats MSDS.

Affected organisms
  • Gram negative and gram positive bacteria
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of bleeding can be increased when Meclocycline is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of bleeding can be increased when Meclocycline is combined with (S)-Warfarin.
4-hydroxycoumarinThe risk or severity of bleeding can be increased when Meclocycline is combined with 4-hydroxycoumarin.
4-OxoretinolThe risk or severity of pseudotumor cerebri and elevated intracranial pressure can be increased when 4-Oxoretinol is combined with Meclocycline.
AcenocoumarolThe risk or severity of bleeding can be increased when Meclocycline is combined with Acenocoumarol.
Acetylcysteine zincAcetylcysteine zinc can cause a decrease in the absorption of Meclocycline resulting in a reduced serum concentration and potentially a decrease in efficacy.
AcetyldigoxinMeclocycline can cause an increase in the absorption of Acetyldigoxin resulting in an increased serum concentration and potentially a worsening of adverse effects.
AcitretinThe risk or severity of pseudotumor cerebri and elevated intracranial pressure can be increased when Acitretin is combined with Meclocycline.
Adenovirus type 7 vaccine liveThe therapeutic efficacy of Adenovirus type 7 vaccine live can be decreased when used in combination with Meclocycline.
AlitretinoinThe risk or severity of pseudotumor cerebri and elevated intracranial pressure can be increased when Alitretinoin is combined with Meclocycline.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

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Food Interactions
Not Available

References

General 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. 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]
  3. Meclocycline Phase II Trial: Oral Mucositis [Link]
External Links
PubChem Compound
54676539
PubChem Substance
347829216
ChemSpider
16735890
ChEBI
135772
ChEMBL
CHEMBL1237124
Wikipedia
Meclocycline
ATC Codes
D10AF04 — Meclocycline
MSDS
Download (316 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentOral Mucositis / Vesicular Stomatitis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilitySolubleMSDS
Predicted Properties
PropertyValueSource
Water Solubility0.542 mg/mLALOGPS
logP0.11ALOGPS
logP-2.9ChemAxon
logS-2.9ALOGPS
pKa (Strongest Acidic)2.61ChemAxon
pKa (Strongest Basic)7.76ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count9ChemAxon
Hydrogen Donor Count6ChemAxon
Polar Surface Area181.62 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity118.47 m3·mol-1ChemAxon
Polarizability45.05 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
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 / Tetralins / Aryl ketones / 1-hydroxy-2-unsubstituted benzenoids / Cyclohexenones / Aryl chlorides / Vinylogous acids / Tertiary alcohols / Trialkylamines
show 9 more
Substituents
Tetracycline / Tetracene / Naphthacene / Anthracene carboxylic acid or derivatives / Tetralin / Aryl ketone / 1-hydroxy-2-unsubstituted benzenoid / Cyclohexenone / Aryl chloride / Aryl halide
show 26 more
Molecular Framework
Aromatic homopolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Yes
Actions
Antagonist
General Function
Trna binding
Specific Function
One of the primary rRNA binding proteins, it binds directly to 16S rRNA where it nucleates assembly of the head domain of the 30S subunit. Is located at the subunit interface close to the decoding ...
Gene Name
rpsG
Uniprot ID
P02359
Uniprot Name
30S ribosomal protein S7
Molecular Weight
20018.91 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]

Enzymes

Kind
Protein
Organism
Bacteroides thetaiotaomicron
Pharmacological action
No
Actions
Substrate
General Function
Oxidoreductase activity
Specific Function
Not Available
Gene Name
tetX2
Uniprot ID
Q93L51
Uniprot Name
TetX family tetracycline inactivation enzyme
Molecular Weight
43707.345 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]

Transporters

Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
No
Actions
Substrate
General Function
Porin activity
Specific Function
Forms pores that allow passive diffusion of small molecules across the outer membrane. It is also a receptor for the bacteriophage T2.
Gene Name
ompF
Uniprot ID
P02931
Uniprot Name
Outer membrane protein F
Molecular Weight
39333.105 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]
Kind
Protein
Organism
Escherichia coli
Pharmacological action
Unknown
Actions
Substrate
General Function
Porin activity
Specific Function
Not Available
Gene Name
ompC
Uniprot ID
Q9K597
Uniprot Name
Membrane protein
Molecular Weight
40311.865 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]

Drug created on October 20, 2016 20:57 / Updated on June 04, 2019 07:47