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Identification
NameDalfopristin
Accession NumberDB01764  (EXPT01246)
TypeSmall Molecule
GroupsApproved
Description

Dalfopristin is a combination of two antibiotics (Dalfopristin and quinupristin) used to treat infections by staphylococci and by vancomycin-resistant Enterococcus faecium. It is not effective against Enterococcus faecalis infections. Dalfopristin inhibits the early phase of protein synthesis in the bacterial ribosome and quinupristin inhibits the late phase of protein synthesis.

Structure
Thumb
Synonyms
Dalfopristina
Dalfopristine
Dalfopristinum
External Identifiers
  • RP 54476
  • RP-54476
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixtures
NameLabellerIngredients
SynercidPfizer Laboratories Div Pfizer Inc
SaltsNot Available
Categories
UNIIR9M4FJE48E
CAS number112362-50-2
WeightAverage: 690.847
Monoisotopic: 690.329849908
Chemical FormulaC34H50N4O9S
InChI KeySUYRLXYYZQTJHF-VMBLUXKRSA-N
InChI
InChI=1S/C34H50N4O9S/c1-7-37(8-2)16-17-48(44,45)28-13-15-38-31(28)34(43)47-32(22(3)4)24(6)11-12-29(41)35-14-9-10-23(5)18-25(39)19-26(40)20-30-36-27(21-46-30)33(38)42/h9-12,18,21-22,24-25,28,31-32,39H,7-8,13-17,19-20H2,1-6H3,(H,35,41)/b10-9+,12-11+,23-18+/t24-,25-,28-,31-,32-/m1/s1
IUPAC Name
(6R,7S,10R,11R,12E,17E,19E,21S)-6-[2-(diethylamino)ethanesulfonyl]-21-hydroxy-11,19-dimethyl-10-(propan-2-yl)-9,26-dioxa-3,15,28-triazatricyclo[23.2.1.0³,⁷]octacosa-1(27),12,17,19,25(28)-pentaene-2,8,14,23-tetrone
SMILES
[H]\C1=C(\[H])/C(/C)=C([H])/[C@@]([H])(O)CC(=O)CC2=NC(=CO2)C(=O)N2CC[C@]([H])([C@]2([H])C(=O)O[C@]([H])(C(C)C)[C@]([H])(C)\C([H])=C([H])\C(O)=NC1)S(=O)(=O)CCN(CC)CC
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as macrolide lactams. These are cyclic polyketides containing both a cyclic amide and a cyclic ester group.
KingdomOrganic compounds
Super ClassPhenylpropanoids and polyketides
ClassMacrolide lactams
Sub ClassNot Available
Direct ParentMacrolide lactams
Alternative Parents
Substituents
  • Macrolide lactam
  • Macrolactam
  • Alpha-amino acid ester
  • Heteroaromatic compound
  • Sulfonyl
  • Sulfone
  • Pyrrolidine
  • Oxazole
  • Azole
  • Cyclic ketone
  • Tertiary aliphatic amine
  • Tertiary amine
  • Secondary carboxylic acid amide
  • Secondary alcohol
  • Lactone
  • Lactam
  • Ketone
  • Carboxylic acid ester
  • Carboxamide group
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Monocarboxylic acid or derivatives
  • Carboxylic acid derivative
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Organosulfur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Alcohol
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationFor the treatment of bacterial infections (usually in combination with quinupristin).
PharmacodynamicsDalfopristin is a streptogramin antibiotic, derived from pristinamycin IIA.
Mechanism of actionThe site of action of dalfopristin is the bacterial ribosome. Dalfopristin has been shown to inhibit the early phase of protein synthesis.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingModerate
Metabolism

Converted to an active non-conjugated metabolite by hydrolysis.

Route of eliminationNot Available
Half lifeThe elimination half-life is approximately 0.70 hours.
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Enteric bacteria and other eubacteria
  • Enterococcus faecalis
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.6544
Blood Brain Barrier-0.9286
Caco-2 permeable-0.6574
P-glycoprotein substrateSubstrate0.7988
P-glycoprotein inhibitor INon-inhibitor0.6395
P-glycoprotein inhibitor IINon-inhibitor0.9399
Renal organic cation transporterNon-inhibitor0.9011
CYP450 2C9 substrateNon-substrate0.7897
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.5
CYP450 1A2 substrateNon-inhibitor0.8118
CYP450 2C9 inhibitorNon-inhibitor0.7261
CYP450 2D6 inhibitorNon-inhibitor0.8606
CYP450 2C19 inhibitorNon-inhibitor0.6834
CYP450 3A4 inhibitorNon-inhibitor0.7363
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9392
Ames testNon AMES toxic0.6184
CarcinogenicityNon-carcinogens0.6071
BiodegradationNot ready biodegradable0.6975
Rat acute toxicity2.6096 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9396
hERG inhibition (predictor II)Non-inhibitor0.7254
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Injection, powder, lyophilized, for solutionintravenous
Powder for solutionintravenous
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0716 mg/mLALOGPS
logP2.57ALOGPS
logP1.58ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)11.38ChemAxon
pKa (Strongest Basic)7.09ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count9ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area176.42 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity182.84 m3·mol-1ChemAxon
Polarizability72.94 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General References
  1. Allington DR, Rivey MP: Quinupristin/dalfopristin: a therapeutic review. Clin Ther. 2001 Jan;23(1):24-44. [PubMed:11219478 ]
  2. Lamb HM, Figgitt DP, Faulds D: Quinupristin/dalfopristin: a review of its use in the management of serious gram-positive infections. Drugs. 1999 Dec;58(6):1061-97. [PubMed:10651391 ]
  3. Manzella JP: Quinupristin-dalfopristin: a new antibiotic for severe gram-positive infections. Am Fam Physician. 2001 Dec 1;64(11):1863-6. [PubMed:11764864 ]
  4. Paradisi F, Corti G, Messeri D: Antistaphylococcal (MSSA, MRSA, MSSE, MRSE) antibiotics. Med Clin North Am. 2001 Jan;85(1):1-17. [PubMed:11190346 ]
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB Entries
FDA labelDownload (67.1 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
CyclosporineThe serum concentration of Cyclosporine can be increased when it is combined with Dalfopristin.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Enterococcus faecium
Pharmacological action
yes
Actions
inhibitor
General Function:
Transferase activity, transferring acyl groups
Specific Function:
Inactivates the A compounds of streptogramin antibiotics by acetylation, thus providing resistance to these antibiotics.
Gene Name:
vatD
Uniprot ID:
P50870
Molecular Weight:
23649.22 Da
References
  1. Manfredi R, Sabbatani S: Novel pharmaceutical molecules against emerging resistant gram-positive cocci. Braz J Infect Dis. 2010 Jan-Feb;14(1):96-108. [PubMed:20428664 ]

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. Rubinstein E, Prokocimer P, Talbot GH: Safety and tolerability of quinupristin/dalfopristin: administration guidelines. J Antimicrob Chemother. 1999 Sep;44 Suppl A:37-46. [PubMed:10511396 ]
  2. Lamb HM, Figgitt DP, Faulds D: Quinupristin/dalfopristin: a review of its use in the management of serious gram-positive infections. Drugs. 1999 Dec;58(6):1061-97. [PubMed:10651391 ]
  3. Bearden DT: Clinical pharmacokinetics of quinupristin/dalfopristin. Clin Pharmacokinet. 2004;43(4):239-52. [PubMed:15005638 ]
  4. Delgado G Jr, Neuhauser MM, Bearden DT, Danziger LH: Quinupristin-dalfopristin: an overview. Pharmacotherapy. 2000 Dec;20(12):1469-85. [PubMed:11130220 ]
Comments
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23