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Identification
NameRolitetracycline
Accession NumberDB01301
TypeSmall Molecule
GroupsApproved
DescriptionA pyrrolidinylmethyl tetracycline. [PubChem]
Structure
Thumb
Synonyms
N-(1-Pyrrolidinylmethyl)-tetracycline
N-(Pyrrolidinomethyl)tetracycline
Pyrrolidino-methyl-tetracycline
Reverin
Rolitetraciclina
Rolitetracyclinum
Synterin
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Reverin 275mgPowder, for solution275 mgIntra-articular; Intraperitoneal; Intrapleural; Intrathecal; IntravenousHoechst Canada Inc.1959-12-311996-12-12Canada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIGH9IW85221
CAS number751-97-3
WeightAverage: 527.5662
Monoisotopic: 527.226765047
Chemical FormulaC27H33N3O8
InChI KeyHMEYVGGHISAPJR-IAHYZSEUSA-N
InChI
InChI=1S/C27H33N3O8/c1-26(37)13-7-6-8-16(31)17(13)21(32)18-14(26)11-15-20(29(2)3)22(33)19(24(35)27(15,38)23(18)34)25(36)28-12-30-9-4-5-10-30/h6-8,14-15,20,31,33-34,37-38H,4-5,9-12H2,1-3H3,(H,28,36)/t14-,15-,20-,26+,27-/m0/s1
IUPAC Name
(4S,4aS,5aS,6S,12aS)-4-(dimethylamino)-3,6,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-N-(pyrrolidin-1-ylmethyl)-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide
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)NCN1CCCC1)=C(O)[[email protected]]2N(C)C
Pharmacology
IndicationRolitetracycline is a broad-spectrum antibiotic used in cases needing high concentrations or when oral administration is impractical.
Structured Indications Not Available
PharmacodynamicsNot Available
Mechanism of actionRolitetracycline is a semisynthetic broad-spectrum tetracycline antibiotic used especially for parenteral administration in cases requiring high concentrations or when oral administration is impractical. Rolitetracycline passively diffuses through porin channels in the bacterial membrane and reversibly binds to the 30S ribosomal subunit, preventing binding of tRNA to the mRNA-ribosome complex, and thus interfering with protein synthesis.
TargetKindPharmacological actionActionsOrganismUniProt ID
30S ribosomal protein S9Proteinyes
inhibitor
Escherichia coli (strain K12)P0A7X3 details
16S rRNANucleotideyes
inhibitor
Enteric bacteria and other eubacterianot applicabledetails
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicitySymptoms of overdose include anorexia, nausea, diarrhoea, glossitis, dysphagia, enterocolitis and inflammatory lesions (with monilial overgrowth) in the anogenital region, skin reactions such as maculopapular and erythematous rashes, exfoliative dermatitis, photosensitivity, hypersensitivity reactions such as urticaria, angioneurotic oedema, anaphylaxis, anaphyl-actoid purpura, pericarditis, and exacerbation of systemic lupus erythematosus, benign intracranial hypertension in adults disappearing on discontinuation of the medicine, haematologic abnormalities such as haemolytic anaemia, thrombocytopenia, neutropenia, and eosinophilia. LD50=262 mg/kg (I.P. in rat).
Affected organismsNot Available
Pathways
PathwayCategorySMPDB ID
Rolitetracycline Action PathwayDrug actionSMP00726
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug Interactions
DrugInteractionDrug group
BcgThe therapeutic efficacy of Bcg can be decreased when used in combination with Rolitetracycline.Investigational
Picosulfuric acidThe therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Rolitetracycline.Approved
Food InteractionsNot Available
References
Synthesis Reference

Horacio Alfredo Priestap, Carlos Rappaport, “Process for producing rolitetracycline.” U.S. Patent US3985768, issued September, 1963.

US3985768
General ReferencesNot Available
External Links
ATC CodesJ01AA09
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.7999
Blood Brain Barrier-0.9659
Caco-2 permeable-0.6259
P-glycoprotein substrateSubstrate0.9289
P-glycoprotein inhibitor INon-inhibitor0.875
P-glycoprotein inhibitor IIInhibitor0.7922
Renal organic cation transporterNon-inhibitor0.7671
CYP450 2C9 substrateNon-substrate0.7614
CYP450 2D6 substrateNon-substrate0.7656
CYP450 3A4 substrateSubstrate0.7527
CYP450 1A2 substrateNon-inhibitor0.9068
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.923
CYP450 2C19 inhibitorNon-inhibitor0.8968
CYP450 3A4 inhibitorNon-inhibitor0.926
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8647
Ames testNon AMES toxic0.6931
CarcinogenicityNon-carcinogens0.9246
BiodegradationNot ready biodegradable0.6204
Rat acute toxicity2.7094 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8692
hERG inhibition (predictor II)Inhibitor0.7194
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Powder, for solutionIntra-articular; Intraperitoneal; Intrapleural; Intrathecal; Intravenous275 mg
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
water solubility5.55E+005 mg/LMERCK INDEX (1996)
Predicted Properties
PropertyValueSource
Water Solubility1.81 mg/mLALOGPS
logP-0.08ALOGPS
logP-3.8ChemAxon
logS-2.5ALOGPS
pKa (Strongest Acidic)0.31ChemAxon
pKa (Strongest Basic)8.24ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count10ChemAxon
Hydrogen Donor Count6ChemAxon
Polar Surface Area170.87 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity139.45 m3·mol-1ChemAxon
Polarizability54.05 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassPhenylpropanoids and polyketides
ClassTetracyclines
Sub ClassNot Available
Direct ParentTetracyclines
Alternative Parents
Substituents
  • Tetracycline
  • Tetracene
  • Naphthacene
  • Anthracene carboxylic acid or derivatives
  • Tetralin
  • Aryl ketone
  • Aralkylamine
  • Benzenoid
  • N-alkylpyrrolidine
  • Vinylogous acid
  • Tertiary alcohol
  • Pyrrolidine
  • Tertiary aliphatic amine
  • Tertiary amine
  • Secondary carboxylic acid amide
  • Polyol
  • Ketone
  • Carboxamide group
  • Azacycle
  • Organoheterocyclic compound
  • Enol
  • Carboxylic acid derivative
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Alcohol
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors

Targets

Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
yes
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
Molecular Weight:
14856.105 Da
References
  1. Carrasco-Pancorbo A, Casado-Terrones S, Segura-Carretero A, Fernandez-Gutierrez A: Reversed-phase high-performance liquid chromatography coupled to ultraviolet and electrospray time-of-flight mass spectrometry on-line detection for the separation of eight tetracyclines in honey samples. J Chromatogr A. 2008 Jun 27;1195(1-2):107-16. doi: 10.1016/j.chroma.2008.05.003. Epub 2008 May 10. [PubMed:18501371 ]
  2. Griffin MO, Fricovsky E, Ceballos G, Villarreal F: Tetracyclines: a pleitropic family of compounds with promising therapeutic properties. Review of the literature. Am J Physiol Cell Physiol. 2010 Sep;299(3):C539-48. doi: 10.1152/ajpcell.00047.2010. Epub 2010 Jun 30. [PubMed:20592239 ]
2. 16S rRNA
Kind
Nucleotide
Organism
Enteric bacteria and other eubacteria
Pharmacological action
yes
Actions
inhibitor
References
  1. Pringle M, Fellstrom C, Johansson KE: Decreased susceptibility to doxycycline associated with a 16S rRNA gene mutation in Brachyspira hyodysenteriae. Vet Microbiol. 2007 Jul 20;123(1-3):245-8. Epub 2007 Feb 25. [PubMed:17428623 ]
  2. Kumar S, Kutlin A, Roblin P, Kohlhoff S, Bodetti T, Timms P, Hammerschlag MR: Isolation and antimicrobial susceptibilities of Chlamydial isolates from Western barred bandicoots. J Clin Microbiol. 2007 Feb;45(2):392-4. Epub 2006 Nov 22. [PubMed:17122017 ]
  3. Ross JI, Eady EA, Cove JH, Cunliffe WJ: 16S rRNA mutation associated with tetracycline resistance in a gram-positive bacterium. Antimicrob Agents Chemother. 1998 Jul;42(7):1702-5. [PubMed:9661007 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
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Drug created on June 30, 2007 08:26 / Updated on August 17, 2016 12:23