Virginiamycin M1

Identification

Name
Virginiamycin M1
Accession Number
DB01669  (EXPT03225)
Type
Small Molecule
Groups
Experimental
Description

Pristinamycin IIA is a macrolide antibiotic. It is a member of the streptogramin A group of antibiotics and one component of pristinamycin (the other being pristinamycin IA). It is produced by Streptomyces graminofaciens and other bacteria.

Structure
Thumb
Synonyms
  • Mikamycin A
  • Ostreogrycin A
  • Pristinamycin IIA
  • Streptogramin A
External IDs
NSC-244426 / NSC-87432 / PA-114A / RP-12536 / RPR-132552 / RPR132552
Categories
UNII
8W4UOL59AZ
CAS number
21411-53-0
Weight
Average: 525.5934
Monoisotopic: 525.247500489
Chemical Formula
C28H35N3O7
InChI Key
DAIKHDNSXMZDCU-FQTGFAPKSA-N
InChI
InChI=1S/C28H35N3O7/c1-17(2)26-19(4)9-10-24(34)29-11-5-7-18(3)13-20(32)14-21(33)15-25-30-22(16-37-25)27(35)31-12-6-8-23(31)28(36)38-26/h5,7-10,13,16-17,19-20,26,32H,6,11-12,14-15H2,1-4H3,(H,29,34)/b7-5+,10-9+,18-13+/t19-,20-,26-/m1/s1
IUPAC Name
(10R,11R,12E,17E,19E,21S)-21-hydroxy-11,19-dimethyl-10-(propan-2-yl)-9,26-dioxa-3,15,28-triazatricyclo[23.2.1.0³,⁷]octacosa-1(27),6,12,17,19,25(28)-hexaene-2,8,14,23-tetrone
SMILES
CC(C)[C@H]1OC(=O)C2=CCCN2C(=O)C2=COC(=N2)CC(=O)C[C@H](O)\C=C(/C)\C=C\CNC(=O)\C=C\[C@H]1C

Pharmacology

Indication

For the treatment of bacterial infections.

Pharmacodynamics
Not Available
Mechanism of action

Virginiamycin M1 is a macrocyclic lactone antibiotic that acts syngeristically with the structurally unrelated cyclic depsipeptides more commonly known as the virginiamycins B (ostreogrycin B or streptogramin B) and S to inhibit peptide elongation. This is achieved by blocking formation of a peptide bond between the growing peptide chain (peptidyl-tRNA) linked to the 50S ribosome and aminoacyl-tRNA. Virginiamycin M1 has proven to be highly active against Gram positive bacteria, particularly methicillin-resistant S. aureus.

TargetActionsOrganism
UStreptogramin A acetyltransferaseNot AvailableEnterococcus faecium
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Bacteria
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Virginiamycin M1.
Picosulfuric acidThe therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Virginiamycin M1.
WarfarinThe risk or severity of bleeding can be increased when Virginiamycin M1 is combined with Warfarin.
Food Interactions
Not Available

References

General References
  1. US Biological [Link]
External Links
KEGG Compound
C11299
PubChem Compound
5459319
PubChem Substance
46506471
ChemSpider
10222381
ChEBI
9997
ChEMBL
CHEMBL1236670
HET
VIR
Wikipedia
Pristinamycin_IIA
PDB Entries
1khr / 1n8r / 1yit / 4hus / 4u25

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

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

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityPoorly soluble in waterNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0601 mg/mLALOGPS
logP2.6ALOGPS
logP2.38ChemAxon
logS-3.9ALOGPS
pKa (Strongest Acidic)11.38ChemAxon
pKa (Strongest Basic)2.19ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area139.04 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity144.17 m3·mol-1ChemAxon
Polarizability55.74 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.7861
Blood Brain Barrier-0.9659
Caco-2 permeable-0.6999
P-glycoprotein substrateSubstrate0.7225
P-glycoprotein inhibitor INon-inhibitor0.7261
P-glycoprotein inhibitor IINon-inhibitor0.8885
Renal organic cation transporterNon-inhibitor0.8822
CYP450 2C9 substrateNon-substrate0.85
CYP450 2D6 substrateNon-substrate0.8337
CYP450 3A4 substrateSubstrate0.6184
CYP450 1A2 substrateNon-inhibitor0.7669
CYP450 2C9 inhibitorNon-inhibitor0.843
CYP450 2D6 inhibitorNon-inhibitor0.9163
CYP450 2C19 inhibitorNon-inhibitor0.7838
CYP450 3A4 inhibitorNon-inhibitor0.9423
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9459
Ames testNon AMES toxic0.6864
CarcinogenicityNon-carcinogens0.8613
BiodegradationNot ready biodegradable0.786
Rat acute toxicity2.6179 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9482
hERG inhibition (predictor II)Non-inhibitor0.8977
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 GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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 macrolide lactams. These are cyclic polyketides containing both a cyclic amide and a cyclic ester group.
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Macrolide lactams
Sub Class
Not Available
Direct Parent
Macrolide lactams
Alternative Parents
Macrolactams / Alpha amino acids and derivatives / 2-heteroaryl carboxamides / Tertiary carboxylic acid amides / Enoate esters / Heteroaromatic compounds / Oxazoles / Pyrrolines / Secondary alcohols / Lactones
show 10 more
Substituents
Macrolide lactam / Macrolactam / Alpha-amino acid or derivatives / 2-heteroaryl carboxamide / Azole / Oxazole / Heteroaromatic compound / Pyrroline / Tertiary carboxylic acid amide / Enoate ester
show 24 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
cyclic ketone, 1,3-oxazoles, secondary alcohol, macrolide antibiotic, enamide, lactam, pyrroline, macrolide (CHEBI:9997)

Targets

Kind
Protein
Organism
Enterococcus faecium
Pharmacological action
Unknown
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
Uniprot Name
Streptogramin A acetyltransferase
Molecular Weight
23649.22 Da
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:17139284]
  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:17016423]

Drug created on June 13, 2005 07:24 / Updated on October 01, 2018 13:07