Identification

Name
Oritavancin
Accession Number
DB04911
Type
Small Molecule
Groups
Approved, Investigational
Description

Oritavancin (also known as LY333328) is an investigational glycopeptide antibiotic with bactericidal activity effective in treating infections caused by Gram-positive organisms. The clinical efficacy of oritavancin has not yet been determined.

Structure
Thumb
Synonyms
  • Chlorobiphenyl-chloroeremomycin
External IDs
LY-333328 / LY333328
Product Ingredients
IngredientUNIICASInChI Key
Oritavancin diphosphateVL1P93MKZN192564-14-0Not applicable
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
OrbactivInjection, powder, lyophilized, for solution400 mg/1IntravenousThe Medicines Company2014-09-01Not applicableUs
OrbactivInjection, powder, lyophilized, for solution400 mg/1IntravenousThe Medicines Company2014-09-012014-08-12Us
OrbactivInjection, powder, lyophilized, for solution400 mg/1IntravenousMelinta Therapeutics, Inc.2014-09-01Not applicableUs
Categories
UNII
PUG62FRZ2E
CAS number
171099-57-3
Weight
Average: 1793.101
Monoisotopic: 1790.564106447
Chemical Formula
C86H97Cl3N10O26
InChI Key
VHFGEBVPHAGQPI-LXKZPTCJSA-N
InChI
InChI=1S/C86H97Cl3N10O26/c1-35(2)22-51(92-7)77(110)98-67-69(105)42-15-20-55(49(88)24-42)120-57-26-44-27-58(73(57)125-84-74(71(107)70(106)59(34-100)122-84)124-62-32-86(6,76(109)37(4)119-62)93-33-38-8-10-39(11-9-38)40-12-17-45(87)18-13-40)121-56-21-16-43(25-50(56)89)72(123-61-31-85(5,91)75(108)36(3)118-61)68-82(115)97-66(83(116)117)48-28-46(101)29-54(103)63(48)47-23-41(14-19-53(47)102)64(79(112)99-68)96-80(113)65(44)95-78(111)52(30-60(90)104)94-81(67)114/h8-21,23-29,35-37,51-52,59,61-62,64-72,74-76,84,92-93,100-103,105-109H,22,30-34,91H2,1-7H3,(H2,90,104)(H,94,114)(H,95,111)(H,96,113)(H,97,115)(H,98,110)(H,99,112)(H,116,117)/t36-,37-,51+,52-,59+,61-,62-,64+,65+,66-,67+,68-,69+,70+,71-,72+,74+,75-,76-,84-,85-,86-/m0/s1
IUPAC Name
(1S,2R,18R,19R,22S,25R,28R,40S)-2-{[(2R,4S,5R,6S)-4-amino-5-hydroxy-4,6-dimethyloxan-2-yl]oxy}-22-(carbamoylmethyl)-5,15-dichloro-48-{[(2S,3R,4S,5S,6R)-3-{[(2S,4S,5R,6S)-4-({[4-(4-chlorophenyl)phenyl]methyl}amino)-5-hydroxy-4,6-dimethyloxan-2-yl]oxy}-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}-18,32,35,37-tetrahydroxy-19-[(2R)-4-methyl-2-(methylamino)pentanamido]-20,23,26,42,44-pentaoxo-7,13-dioxa-21,24,27,41,43-pentaazaoctacyclo[26.14.2.2³,⁶.2¹⁴,¹⁷.1⁸,¹².1²⁹,³³.0¹⁰,²⁵.0³⁴,³⁹]pentaconta-3,5,8,10,12(48),14,16,29(45),30,32,34(39),35,37,46,49-pentadecaene-40-carboxylic acid
SMILES
[H][C@]12NC(=O)[C@]([H])(NC(=O)[C@]3([H])NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](NC(=O)[C@@H](CC(C)C)NC)[C@H](O)C4=CC(Cl)=C(OC5=C(O[C@@H]6O[C@H](CO)[C@@H](O)[C@H](O)[C@H]6O[C@H]6C[C@](C)(NCC7=CC=C(C=C7)C7=CC=C(Cl)C=C7)[C@@H](O)[C@H](C)O6)C(OC6=C(Cl)C=C(C=C6)[C@H]1O[C@H]1C[C@](C)(N)[C@@H](O)[C@H](C)O1)=CC3=C5)C=C4)C1=CC(=C(O)C=C1)C1=C(C=C(O)C=C1O)[C@H](NC2=O)C(O)=O

Pharmacology

Indication

Investigated for use/treatment in bacterial infection and skin infections/disorders.

Associated Conditions
Pharmacodynamics

Oritavancin is an investigational glycopeptide antibiotic with bactericidal activity effective in treating infections caused by Gram-positive organisms. It treats complicated skin and skin structure infections. This new drug will be tested for treatment of bacteraemia and nosocomial pneumonia. It demonstrates similar activity to vancomycin, but it has stronger activity against Staphylococcus and Enterococcus. The pharmacokinetics and pharmacodynamics of oritavancin appear to be favourable and once-daily dosing is likely. The incidence of multi-drug resistant bacteria is increasing and explorations into additional treatment options are essential.

Mechanism of action

Oritavancin is a glycopeptide antibiotic. This class of drugs inhibit the synthesis of cell walls in susceptible microbes by inhibiting peptidoglycan synthesis. They bind to the amino acids within the cell wall preventing the addition of new units to the peptidoglycan. In particular they bind to acyl-D-alanyl-D-alanine in peptidoglycan.

Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life

The mean (range) plasma terminal half-life of oritavancin is 195.4 (135.8-273.8) hours across all dose levels from 0.05-0.5 mg/kg.

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Gram-positive Bacteria
  • Streptococcus pyogenes
  • Streptococcus pneumoniae
  • Staphylococcus aureus
  • 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 Oritavancin is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of bleeding can be increased when Oritavancin is combined with (S)-Warfarin.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be increased when combined with Oritavancin.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be increased when combined with Oritavancin.
4-MethoxyamphetamineThe metabolism of 4-Methoxyamphetamine can be increased when combined with Oritavancin.
5-androstenedioneThe metabolism of 5-androstenedione can be increased when combined with Oritavancin.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be increased when combined with Oritavancin.
AbemaciclibThe metabolism of Abemaciclib can be increased when combined with Oritavancin.
AbirateroneThe metabolism of Abiraterone can be increased when combined with Oritavancin.
AcebutololThe metabolism of Acebutolol can be increased when combined with Oritavancin.
Food Interactions
Not Available

References

General References
  1. Citron DM, Kwok YY, Appleman MD: In vitro activity of oritavancin (LY333328), vancomycin, clindamycin, and metronidazole against Clostridium perfringens, Propionibacterium acnes, and anaerobic Gram-positive cocci. Anaerobe. 2005 Feb-Apr;11(1-2):93-5. Epub 2004 Dec 10. [PubMed:16701537]
  2. Ward KE, Mersfelder TL, LaPlante KL: Oritavancin--an investigational glycopeptide antibiotic. Expert Opin Investig Drugs. 2006 Apr;15(4):417-29. [PubMed:16548791]
  3. Bhavnani SM, Passarell JA, Owen JS, Loutit JS, Porter SB, Ambrose PG: Pharmacokinetic-pharmacodynamic relationships describing the efficacy of oritavancin in patients with Staphylococcus aureus bacteremia. Antimicrob Agents Chemother. 2006 Mar;50(3):994-1000. [PubMed:16495262]
  4. Mercier RC, Hrebickova L: Oritavancin: a new avenue for resistant Gram-positive bacteria. Expert Rev Anti Infect Ther. 2005 Jun;3(3):325-32. [PubMed:15954849]
  5. Fetterly GJ, Ong CM, Bhavnani SM, Loutit JS, Porter SB, Morello LG, Ambrose PG, Nicolau DP: Pharmacokinetics of oritavancin in plasma and skin blister fluid following administration of a 200-milligram dose for 3 days or a single 800-milligram dose. Antimicrob Agents Chemother. 2005 Jan;49(1):148-52. [PubMed:15616289]
  6. Bhavnani SM, Owen JS, Loutit JS, Porter SB, Ambrose PG: Pharmacokinetics, safety, and tolerability of ascending single intravenous doses of oritavancin administered to healthy human subjects. Diagn Microbiol Infect Dis. 2004 Oct;50(2):95-102. [PubMed:15474317]
External Links
KEGG Compound
C12034
PubChem Compound
16136912
PubChem Substance
175426900
ChemSpider
17286443
ChEBI
82699
ChEMBL
CHEMBL1688530
Wikipedia
Oritavancin
ATC Codes
J01XA05 — Oritavancin
FDA label
Download (527 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableHealthy Volunteers3
1CompletedTreatmentHealthy Volunteers3
1RecruitingTreatmentGram Positive Bacterial Infections1
2CompletedTreatmentAbscesses / Cellulitis / Staphylococcal Skin Infections / Streptococcal Infections / Wounds and Injuries1
3CompletedTreatmentAbscesses / Cellulitis / Systemic Inflammation / Wound Infections2
4CompletedOtherSkin Diseases, Bacterial1
4CompletedTreatmentAcute acute bacterial skin and skin structure infections1
Not AvailableCompletedNot AvailableInfections, Gram-Positive Bacterial1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, powder, lyophilized, for solutionIntravenous400 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US8420592No2013-04-162029-08-29Us
US5840684No1998-11-242016-11-24Us
US5998581No1999-12-072017-11-12Us
US9649352No2017-05-162035-07-16Us
US9682061No2017-06-202030-04-26Us

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0588 mg/mLALOGPS
logP1.92ALOGPS
logP-0.094ChemAxon
logS-4.5ALOGPS
pKa (Strongest Acidic)2.98ChemAxon
pKa (Strongest Basic)10.08ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count27ChemAxon
Hydrogen Donor Count20ChemAxon
Polar Surface Area560.98 Å2ChemAxon
Rotatable Bond Count19ChemAxon
Refractivity441.59 m3·mol-1ChemAxon
Polarizability176.06 Å3ChemAxon
Number of Rings13ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.6087
Blood Brain Barrier-0.9905
Caco-2 permeable-0.7039
P-glycoprotein substrateSubstrate0.9233
P-glycoprotein inhibitor INon-inhibitor0.8502
P-glycoprotein inhibitor IINon-inhibitor0.9262
Renal organic cation transporterNon-inhibitor0.9503
CYP450 2C9 substrateNon-substrate0.8721
CYP450 2D6 substrateNon-substrate0.8153
CYP450 3A4 substrateSubstrate0.6616
CYP450 1A2 substrateNon-inhibitor0.881
CYP450 2C9 inhibitorNon-inhibitor0.8283
CYP450 2D6 inhibitorNon-inhibitor0.8541
CYP450 2C19 inhibitorNon-inhibitor0.8122
CYP450 3A4 inhibitorNon-inhibitor0.6912
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7622
Ames testNon AMES toxic0.6154
CarcinogenicityNon-carcinogens0.8151
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.6222 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9983
hERG inhibition (predictor II)Non-inhibitor0.5464
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as oligopeptides. These are organic compounds containing a sequence of between three and ten alpha-amino acids joined by peptide bonds.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Oligopeptides
Alternative Parents
Cyclic peptides / Aminoglycosides / Phenolic glycosides / Leucine and derivatives / Chlorinated biphenyls / N-acyl-alpha amino acids and derivatives / Alpha amino acid amides / Diarylethers / Disaccharides / O-glycosyl compounds
show 29 more
Substituents
Alpha-oligopeptide / Cyclic alpha peptide / Aminoglycoside core / Phenolic glycoside / Leucine or derivatives / N-acyl-alpha amino acid or derivatives / Chlorinated biphenyl / Biphenyl / Alpha-amino acid amide / O-glycosyl compound
show 55 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
disaccharide derivative, glycopeptide (CHEBI:82699)

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
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
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid 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 oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Rosenthal S, Decano AG, Bandali A, Lai D, Malat GE, Bias TE: Oritavancin (Orbactiv): A New-Generation Lipoglycopeptide for the Treatment Of Acute Bacterial Skin and Skin Structure Infections. P T. 2018 Mar;43(3):143-179. [PubMed:29491695]
  2. Oritavancin FDA label [File]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da

Drug created on October 21, 2007 16:23 / Updated on November 02, 2018 08:50