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Identification
Name Demeclocycline
Accession Number DB00618 (APRD00272)
Type small molecule
Groups approved
Description

A tetracycline analog having a 7-chloro and a 6-methyl. Because it is excreted more slowly than tetracycline, it maintains effective blood levels for longer periods of time. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Brand names
  • 6-Demethyl-7-chlorotetracycline
  • 6-Demethylchlorotetracycline
  • 7-Chloro-6-demethyltetracycline
  • Bioterciclin
  • Clortetrin
  • Declomycin
  • Deganol
  • Demeclociclina [INN-Spanish]
  • Demeclocycline [USAN:BAN]
  • Demeclocycline HCL
  • Demeclocycline hydrochloride
  • Demeclocyclinum [INN-Latin]
  • Demeclor
  • Demethylchlorotetracycline
  • Demethylchlortetracyclin
  • Demethylchlortetracycline
  • Demethylchlortetracycline hydrochloride
  • Demethylchlortetracyclinum
  • Demetraclin
  • Diuciclin
  • DMCT
  • DMCT (antibiotic)
  • Elkamicina
  • Ledermycin
  • Ledermycin hydrochloride
  • Methylchlorotetracycline
  • Mexocine
  • Novotriclina
  • Perciclina
  • Sumaclina
  • Tri-demethylchlortetracycline
Brand name mixtures Not Available
Categories
  • Anti-Bacterial Agents
  • Tetracyclines
CAS number 127-33-3
Weight Average: 464.853
Monoisotopic: 464.098643365
Chemical Formula C21H21ClN2O8
InChI Key InChIKey=HXPZLYXFFSKHJA-GNCUHUTISA-N
InChI
InChI=1S/C21H21ClN2O8/c1-24(2)14-7-5-6-10(16(27)12-9(25)4-3-8(22)11(12)15(6)26)18(29)21(7,32)19(30)13(17(14)28)20(23)31/h3-4,6-7,14-15,25-27,31-32H,5,23H2,1-2H3/b20-13+/t6-,7-,14-,15-,21-/m0/s1
Plain Text
IUPAC Name
(2E,4S,4aS,5aS,6S,12aS)-2-[amino(hydroxy)methylidene]-7-chloro-4-(dimethylamino)-6,10,11,12a-tetrahydroxy-1,2,3,4,4a,5,5a,6,12,12a-decahydrotetracene-1,3,12-trione
SMILES
[H][C@]12C[C@@]3([H])[C@H](N(C)C)C(=O)\C(=C(\N)O)C(=O)[C@@]3(O)C(=O)C1=C(O)C1=C([C@H]2O)C(Cl)=CC=C1O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Tetracyclines
Substructures
  • Tetracyclines
  • Hydroxy Compounds
  • Benzyl Alcohols and Derivatives
  • Naphthalenes
  • Phenols and Derivatives
  • Amino Ketones
  • Phenylpropenes
  • Benzene and Derivatives
  • Aryl Halides
  • Halobenzenes
  • Aliphatic and Aryl Amines
  • Alcohols and Polyols
  • Aromatic compounds
  • Cinnamaldehydes
  • Ketenes and Derivatives
  • Phenyl Esters
  • Enols
  • Ketones
Pharmacology
Indication Used primarily to treat Lyme disease, acne, and bronchitis. Also indicated (but rarely used) to treat urinary tract infections, gum disease, malaria, and other bacterial infections such as gonorrhea and chlamydia. One of its other registered uses is the treatment of hyponatremia (low blood sodium concentration) due to the syndrome of inappropriate antidiuretic hormone (SIADH) where fluid restriction alone has been ineffective.
Pharmacodynamics Demeclocycline is a tetracycline antibiotic active against the following microorganisms: Rickettsiae (Rocky Mountain spotted fever, typhus fever and the typhus group, Q fever, rickettsial pox, tick fevers), Mycoplasma pneumoniae (PPLO, Eaton agent), agents of psittacosis and ornithosis, agents of lymphogranulomavenereum and granuloma inguinale, the spirochetal agent of relapsing fever (Borrelia recurrentis), Haemophilus ducreyi (chancroid), Yersinia pestis, Pasteurella pestis and Pasteurella tularensis, Bartonella bacilliformis, Bacteroides species, Vibrio comma and Vibrio fetus, and Brucella species (in conjunction with streptomycin). Demeclocycline inhibits cell growth by inhibiting translation. Demeclocycline is lipophilic and can easily pass through the cell membrane or passively diffuses through porin channels in the bacterial membrane. Demeclocycline is bacteriostatic (it impairs bacterial growth but does not kill bacteria directly). Because it is excreted more slowly than tetracycline, it maintains effective blood levels for longer periods of time.
Mechanism of action Demeclocycline inhibits cell growth by inhibiting translation. It binds (reversibly) to the 30S and 50S ribosomal subunit and prevents the amino-acyl tRNA from binding to the A site of the ribosome, which impairs protein synthesis by bacteria. The binding is reversible in nature. The use in SIADH actually relies on a side-effect of tetracycline antibiotics; many may cause diabetes insipidus (dehydration due to the inability to concentrate urine). It is not completely understood why demeclocycline impairs the action of antidiuretic hormone, but it is thought that it blocks the binding of the hormone to its receptor.
Absorption Tetracyclines are readily absorbed.
Volume of distribution Not Available
Protein binding 41-50%
Metabolism

Hepatic
Route of elimination Demeclocycline hydrochloride, like other tetracyclines, is concentrated in the liver and excreted into the bile where it is found in much higher concentrations than in the blood. Following a single 150 mg dose of demeclocycline hydrochloride in normal volunteers, 44% (n = 8) was excreted in urine and 13% and 46%, respectively, were excreted in feces in two patients within 96 hours as active drug.
Half life 10-17 hours
Clearance
  • Renal cl=35 mL/min/1.73 m2
Toxicity Oral, rat: LD50 = 2372 mg/kg
Affected organisms
  • Enteric bacteria and other eubacteria
Pathways
Pathway Name SMPDB ID
Smp00290 Demeclocycline Pathway SMP00290
Pharmacoeconomics
Manufacturers
  • Lederle laboratories div american cyanamid co
  • Stiefel laboratories inc
  • Amneal pharmaceutical
  • Barr laboratories inc
  • Convenant pharma inc
  • Impax laboratories inc
  • Abbott laboratories pharmaceutical products div
  • Elkins sinn div ah robins co inc
  • John j ferrante
  • Heather drug co inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Laboratorios atral sarl
  • Mm mast and co
  • Mutual pharmaceutical co inc
  • Mylan pharmaceuticals inc
  • Purepac pharmaceutical co
  • Private formulations inc
  • Roxane laboratories inc
  • Sandoz inc
  • Superpharm corp
  • Valeant pharmaceuticals international
  • Warner chilcott inc
  • Watson laboratories inc
  • West ward pharmaceutical corp
  • Wyeth ayerst laboratories
  • Alpharma us pharmaceuticals division
  • Proter laboratory spa
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Declomycin 300 mg tablet 22.29 USD tablet
Demeclocycline 300 mg tablet 17.06 USD tablet
Declomycin 150 mg tablet 12.31 USD tablet
Demeclocycline 150 mg tablet 9.42 USD tablet
Patents Not Available
Properties
State solid
Melting point 220-223 oC
Experimental Properties
Property Value Source
water solubility 1520 mg/L PhysProp
logP 0.2 PhysProp
logS -2.52 [ADME Research, USCD] PhysProp
Predicted Properties
Property Value Source
water solubility 5.30e-01 g/l ALOGPS
logP -0.07 ALOGPS
logP -0.02 ChemAxon Molconvert
logS -2.94 ALOGPS
pKa 7.45 ChemAxon Molconvert
hydrogen acceptor count 10 ChemAxon Molconvert
hydrogen donor count 6 ChemAxon Molconvert
polar surface area 181.62 ChemAxon Molconvert
rotatable bond count 1 ChemAxon Molconvert
refractivity 123.34 ChemAxon Molconvert
polarizability 43.75 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. De Troyer A, Demanet JC: Correction of antidiuresis by demeclocycline. N Engl J Med. 1975 Oct 30;293(18):915-8. Pubmed
External Links
Resource Link
KEGG Drug D00290 Link_out
PubChem Compound 5311063 Link_out
PubChem Substance 46506314 Link_out
ChemSpider 4470600 Link_out
ChEBI 4392 Link_out
ChEMBL 4392 Link_out
Therapeutic Targets Database DAP000402 Link_out
PharmGKB PA449228 Link_out
Drug Product Database 2169924 Link_out
RxList http://www.rxlist.com/cgi/generic3/demeclocycline.htm Link_out
Drugs.com http://www.drugs.com/cdi/demeclocycline.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Demeclocycline Link_out
ATC Codes
  • D06AA01
  • J01AA01
AHFS Codes
  • 08:12.24
PDB Entries
FDA label Not Available
MSDS show (51.5 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Avoid milk and multivalent ions.
  • Take on an empty stomach.
Targets

1. 30S ribosomal protein S9

Pharmacological action: yes
Actions: inhibitor

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

Organism class: bacterial
UniProt ID: P0A7X3 Link_out
Gene: rpsI
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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

2. 30S ribosomal protein S4

Pharmacological action: yes
Actions: inhibitor

Also functions as a rho-dependent antiterminator of rRNA transcription, increasing the synthesis of rRNA under conditions of excess protein, allowing a more rapid return to homeostasis. Binds directly to RNA polymerase

Organism class: bacterial
UniProt ID: P0A7V8 Link_out
Gene: rpsD
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:05

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.