Identification

Name
Quinupristin
Accession Number
DB01369
Type
Small Molecule
Groups
Approved
Description

Quinupristin/dalfopristin is a combination of two antibiotics used to treat infections by staphylococci and by vancomycin-resistant Enterococcus faecium. Dalfopristin inhibits the early phase of protein synthesis in the bacterial ribosome and quinupristin inhibits the late phase of protein synthesis. The combination of the two components acts synergistically and is more effective in vitro than each component alone.

Structure
Thumb
Synonyms
  • Quinupristin
External IDs
RP 57669
Product Ingredients
IngredientUNIICASInChI Key
Quinupristin mesylate91VAC8654ENot AvailableZNQOUMVWYLNQRW-FDQSXSIVSA-N
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
SynercidQuinupristin (180 mg/6mL) + Dalfopristin (420 mg/6mL)InjectionIntravenousMonarch Pharmaceuticals, Inc.2006-11-222006-11-22Us
SynercidQuinupristin (150 mg) + Dalfopristin (350 mg)Powder, for solutionIntravenousMonarch Pharmaceuticals, Inc.2000-07-052008-05-28Canada
SynercidQuinupristin (150 mg/5mL) + Dalfopristin (350 mg/5mL)Injection, powder, lyophilized, for solutionIntravenousPfizer Laboratories Div Pfizer Inc.1999-09-21Not applicableUs
Categories
UNII
23OW28RS7P
CAS number
120138-50-3
Weight
Average: 1022.23
Monoisotopic: 1021.473160567
Chemical Formula
C53H67N9O10S
InChI Key
WTHRRGMBUAHGNI-LCYNINFDSA-N
InChI
InChI=1S/C53H67N9O10S/c1-6-37-50(68)61-23-11-14-38(61)51(69)59(5)40(26-32-16-18-36(19-17-32)58(3)4)52(70)62-28-35(30-73-43-29-60-24-20-33(43)21-25-60)42(64)27-39(62)47(65)57-45(34-12-8-7-9-13-34)53(71)72-31(2)44(48(66)55-37)56-49(67)46-41(63)15-10-22-54-46/h7-10,12-13,15-19,22,31,33,35,37-40,43-45,63H,6,11,14,20-21,23-30H2,1-5H3,(H,55,66)(H,56,67)(H,57,65)/t31-,35+,37-,38+,39+,40+,43-,44+,45+/m1/s1
IUPAC Name
N-[(3S,6S,12R,15S,16R,19S,22S,25R)-25-{[(3S)-1-azabicyclo[2.2.2]octan-3-ylsulfanyl]methyl}-3-{[4-(dimethylamino)phenyl]methyl}-12-ethyl-4,16-dimethyl-2,5,11,14,18,21,24-heptaoxo-19-phenyl-17-oxa-1,4,10,13,20-pentaazatricyclo[20.4.0.0⁶,¹⁰]hexacosan-15-yl]-3-hydroxypyridine-2-carboxamide
SMILES
[H][C@@]12CCCN1C(=O)[C@@H](CC)NC(=O)[C@@H](NC(=O)C1=NC=CC=C1O)[C@@H](C)OC(=O)[C@@H](NC(=O)[C@]1([H])CC(=O)[C@]([H])(CS[C@@H]3CN4CCC3CC4)CN1C(=O)[C@H](CC1=CC=C(C=C1)N(C)C)N(C)C2=O)C1=CC=CC=C1

Pharmacology

Indication

For the treatment of bacterial infections (usually in combination with dalfopristin).

Associated Conditions
Pharmacodynamics

Quinupristin is a streptogramin antibiotic, derived from pristinamycin I. By inhibiting the bacterial ribosomal subunits, protein synthesis is inhibited thus leading to eventual bacterial cell death or stasis.

Mechanism of action

Quinupristin inhibits the late phase of protein synthesis in the bacterial ribosome. Dalfopristin binds to the 23S portion of the 50S ribosomal subunit, and changes the conformation it, enhancing the binding of quinupristin by a factor of about 100. In addition, it inhibits peptidyl transferase. Quinupristin binds to a nearby site on the 50S ribosomal subunit and prevents elongation of the polypeptide as well as causing incomplete chains to be released.

TargetActionsOrganism
A23S rRNA
inhibitor
Enteric bacteria and other eubacteria
A50S ribosomal protein L10
inhibitor
Shigella flexneri
A50S ribosomal protein L22
inhibitor
Escherichia coli O157:H7
Absorption
Not Available
Volume of distribution
Not Available
Protein binding

Moderate.

Metabolism

Quinupristin is converted to two conjugated active major metabolites, one with glutathione and one with cysteine.

Route of elimination
Not Available
Half life

3.1 hours

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Enteric bacteria and other eubacteria
  • Enterococcus faecalis
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of bleeding can be increased when Quinupristin is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of bleeding can be increased when Quinupristin is combined with (S)-Warfarin.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Quinupristin.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Quinupristin.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Quinupristin.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Quinupristin.
7-ethyl-10-hydroxycamptothecinThe metabolism of 7-ethyl-10-hydroxycamptothecin can be decreased when combined with Quinupristin.
9-aminocamptothecinThe metabolism of 9-aminocamptothecin can be decreased when combined with Quinupristin.
AbemaciclibThe metabolism of Abemaciclib can be decreased when combined with Quinupristin.
AbirateroneThe metabolism of Abiraterone can be decreased when combined with Quinupristin.
Food Interactions
Not Available

References

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
KEGG Drug
D00852
KEGG Compound
C08032
PubChem Compound
5388937
PubChem Substance
46505148
ChemSpider
4470884
ChEMBL
CHEMBL1200649
Therapeutic Targets Database
DAP001288
PharmGKB
PA164749647
Wikipedia
Quinupristin
FDA label
Download (67.1 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentOsteomyelitis1
3TerminatedTreatmentInfections, Gram-Positive Bacterial1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • DSM Corp.
  • Gruppo Lepetit SPA
  • Monarch Pharmacy
  • Sanofi-Aventis Inc.
Dosage forms
FormRouteStrength
InjectionIntravenous
Injection, powder, lyophilized, for solutionIntravenous
Powder, for solutionIntravenous
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0445 mg/mLALOGPS
logP2.99ALOGPS
logP2.18ChemAxon
logS-4.4ALOGPS
pKa (Strongest Acidic)7.45ChemAxon
pKa (Strongest Basic)8.28ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count12ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area231.2 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity272.84 m3·mol-1ChemAxon
Polarizability107.45 Å3ChemAxon
Number of Rings8ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.6848
Blood Brain Barrier-0.9972
Caco-2 permeable-0.648
P-glycoprotein substrateSubstrate0.8607
P-glycoprotein inhibitor INon-inhibitor0.5298
P-glycoprotein inhibitor IINon-inhibitor0.6803
Renal organic cation transporterNon-inhibitor0.8877
CYP450 2C9 substrateNon-substrate0.7898
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.6413
CYP450 1A2 substrateNon-inhibitor0.8804
CYP450 2C9 inhibitorNon-inhibitor0.803
CYP450 2D6 inhibitorNon-inhibitor0.8539
CYP450 2C19 inhibitorNon-inhibitor0.7776
CYP450 3A4 inhibitorNon-inhibitor0.8954
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9155
Ames testNon AMES toxic0.7484
CarcinogenicityNon-carcinogens0.8552
BiodegradationNot ready biodegradable0.9816
Rat acute toxicity2.9306 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9575
hERG inhibition (predictor II)Inhibitor0.7598
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 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 cyclic depsipeptides. These are natural or synthetic compounds having sequences of amino and hydroxy carboxylic acid residues (usually α-amino and α-hydroxy acids) connected in a ring. The residues are commonly but not necessarily regularly alternating.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Peptidomimetics
Sub Class
Depsipeptides
Direct Parent
Cyclic depsipeptides
Alternative Parents
Macrolide lactams / Alpha amino acid esters / Macrolactams / N-acyl-alpha amino acids and derivatives / Pyridinecarboxamides / Quinuclidines / 2-heteroaryl carboxamides / Aniline and substituted anilines / Dialkylarylamines / Piperidinones
show 19 more
Substituents
Cyclic depsipeptide / Macrolide lactam / N-acyl-alpha amino acid or derivatives / Alpha-amino acid ester / Macrolactam / Alpha-amino acid or derivatives / Pyridine carboxylic acid or derivatives / Pyridinecarboxamide / 2-heteroaryl carboxamide / Aniline or substituted anilines
show 42 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

1. 23S rRNA
Kind
Nucleotide
Organism
Enteric bacteria and other eubacteria
Pharmacological action
Yes
Actions
Inhibitor
References
  1. Barthel D, Schlitzer M, Pradel G: Telithromycin and quinupristin-dalfopristin induce delayed death in Plasmodium falciparum. Antimicrob Agents Chemother. 2008 Feb;52(2):774-7. Epub 2007 Dec 3. [PubMed:18056275]
  2. Beyer D, Pepper K: The streptogramin antibiotics: update on their mechanism of action. Expert Opin Investig Drugs. 1998 Apr;7(4):591-9. [PubMed:15991995]
  3. Harms JM, Schlunzen F, Fucini P, Bartels H, Yonath A: Alterations at the peptidyl transferase centre of the ribosome induced by the synergistic action of the streptogramins dalfopristin and quinupristin. BMC Biol. 2004 Apr 1;2:4. [PubMed:15059283]
  4. Dang V, Nanda N, Cooper TW, Greenfield RA, Bronze MS: Part VII. Macrolides, azalides, ketolides, lincosamides, and streptogramins. J Okla State Med Assoc. 2007 Mar;100(3):75-81. [PubMed:17432033]
Kind
Protein
Organism
Shigella flexneri
Pharmacological action
Yes
Actions
Inhibitor
General Function
Structural constituent of ribosome
Specific Function
Protein L10 is also a translational repressor protein. It controls the translation of the rplJL-rpoBC operon by binding to its mRNA (By similarity).Forms part of the ribosomal stalk, playing a cent...
Gene Name
rplJ
Uniprot ID
P0A7J6
Uniprot Name
50S ribosomal protein L10
Molecular Weight
17711.38 Da
References
  1. Barthel D, Schlitzer M, Pradel G: Telithromycin and quinupristin-dalfopristin induce delayed death in Plasmodium falciparum. Antimicrob Agents Chemother. 2008 Feb;52(2):774-7. Epub 2007 Dec 3. [PubMed:18056275]
  2. Harms JM, Schlunzen F, Fucini P, Bartels H, Yonath A: Alterations at the peptidyl transferase centre of the ribosome induced by the synergistic action of the streptogramins dalfopristin and quinupristin. BMC Biol. 2004 Apr 1;2:4. [PubMed:15059283]
  3. Dang V, Nanda N, Cooper TW, Greenfield RA, Bronze MS: Part VII. Macrolides, azalides, ketolides, lincosamides, and streptogramins. J Okla State Med Assoc. 2007 Mar;100(3):75-81. [PubMed:17432033]
Kind
Protein
Organism
Escherichia coli O157:H7
Pharmacological action
Yes
Actions
Inhibitor
General Function
Structural constituent of ribosome
Specific Function
This protein binds specifically to 23S rRNA; its binding is stimulated by other ribosomal proteins, e.g. L4, L17, and L20. It is important during the early stages of 50S assembly. It makes multiple...
Gene Name
rplV
Uniprot ID
P61177
Uniprot Name
50S ribosomal protein L22
Molecular Weight
12226.165 Da
References
  1. Barthel D, Schlitzer M, Pradel G: Telithromycin and quinupristin-dalfopristin induce delayed death in Plasmodium falciparum. Antimicrob Agents Chemother. 2008 Feb;52(2):774-7. Epub 2007 Dec 3. [PubMed:18056275]
  2. Harms JM, Schlunzen F, Fucini P, Bartels H, Yonath A: Alterations at the peptidyl transferase centre of the ribosome induced by the synergistic action of the streptogramins dalfopristin and quinupristin. BMC Biol. 2004 Apr 1;2:4. [PubMed:15059283]
  3. Dang V, Nanda N, Cooper TW, Greenfield RA, Bronze MS: Part VII. Macrolides, azalides, ketolides, lincosamides, and streptogramins. J Okla State Med Assoc. 2007 Mar;100(3):75-81. [PubMed:17432033]
  4. Halling SM, Jensen AE: Intrinsic and selected resistance to antibiotics binding the ribosome: analyses of Brucella 23S rrn, L4, L22, EF-Tu1, EF-Tu2, efflux and phylogenetic implications. BMC Microbiol. 2006 Oct 2;6:84. [PubMed:17014718]
  5. Tu D, Blaha G, Moore PB, Steitz TA: Structures of MLSBK antibiotics bound to mutated large ribosomal subunits provide a structural explanation for resistance. Cell. 2005 Apr 22;121(2):257-70. [PubMed:15851032]
  6. Schlunzen F, Harms JM, Franceschi F, Hansen HA, Bartels H, Zarivach R, Yonath A: Structural basis for the antibiotic activity of ketolides and azalides. Structure. 2003 Mar;11(3):329-38. [PubMed:12623020]
  7. Petropoulos AD, Kouvela EC, Starosta AL, Wilson DN, Dinos GP, Kalpaxis DL: Time-resolved binding of azithromycin to Escherichia coli ribosomes. J Mol Biol. 2009 Jan 30;385(4):1179-92. doi: 10.1016/j.jmb.2008.11.042. Epub 2008 Nov 27. [PubMed:19071138]
  8. Champney WS, Miller M: Inhibition of 50S ribosomal subunit assembly in Haemophilus influenzae cells by azithromycin and erythromycin. Curr Microbiol. 2002 Jun;44(6):418-24. [PubMed:12000992]

Enzymes

Kind
Protein
Organism
Humans
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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
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. Bearden DT: Clinical pharmacokinetics of quinupristin/dalfopristin. Clin Pharmacokinet. 2004;43(4):239-52. [PubMed:15005638]
  3. Delgado G Jr, Neuhauser MM, Bearden DT, Danziger LH: Quinupristin-dalfopristin: an overview. Pharmacotherapy. 2000 Dec;20(12):1469-85. [PubMed:11130220]

Drug created on July 06, 2007 14:25 / Updated on December 16, 2018 06:48