Tavaborole

Identification

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Name
Tavaborole
Accession Number
DB09041  (DB05058)
Type
Small Molecule
Groups
Approved, Investigational
Description

Tavaborale is a novel, boron-based topical antifungal medication for the treatment of onychomycosis, a fungal infection of the nail and nail bed due to Trichophyton rubrum or Trichophyton mentagrophytes infection. Tavaborole functions by inhibiting Leucyl-tRNA synthetase, or LeuRS, an essential fungal enzyme required for protein synthesis and for the catalysis of ATP-dependent ligation of L-leucine to tRNA(Leu).

Structure
Thumb
Synonyms
  • 5-Fluoro-1,3-dihydro-1-hydroxy-2,1-benzoxaborole
  • 5-Fluoro-2,1-benzoxaborol-1(3H)-ol
  • Tavaborole
External IDs
AN 2690 / AN-2690 / AN2690
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
KerydinSolution43.5 mg/1mLTopicalPharma Derm, A Division Of Fougera Pharmaceuticals Inc.2014-07-07Not applicableUs
KerydinSolution43.5 mg/1mLTopicalAnacor Pharmaceuticals, Inc.2014-07-072015-06-04Us
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories
UNII
K124A4EUQ3
CAS number
174671-46-6
Weight
Average: 151.93
Monoisotopic: 152.044488
Chemical Formula
C7H6BFO2
InChI Key
LFQDNHWZDQTITF-UHFFFAOYSA-N
InChI
InChI=1S/C7H6BFO2/c9-6-1-2-7-5(3-6)4-11-8(7)10/h1-3,10H,4H2
IUPAC Name
5-fluoro-1,3-dihydro-2,1-benzoxaborol-1-ol
SMILES
OB1OCC2=CC(F)=CC=C12

Pharmacology

Indication

Indicated for the treatment of onychomycosis (a fungal infection) of the toenails due to Trichophyton rubrum or Trichophyton mentagrophytes.

Associated Conditions
Pharmacodynamics

After a single dose, the mean (± standard deviation) peak concentration (Cmax) of tavaborole was 3.54 ± 2.26 ng/mL (n=21 with measurable concentrations, range 0.618-10.2 ng/mL, LLOQ=0.5 ng/mL), and the mean AUClast was 44.4 ± 25.5 nghr/mL (n=21). After 2 weeks of daily dosing, the mean Cmax was 5.17 ± 3.47 ng/mL (n=24, range 1.51­-12.8 ng/mL), and the mean AUCτ was 75.8 ± 44.5 nghr/mL.

Mechanism of action

Tavaborole exerts its antifungal activity by blocking cellular protein synthesis through the formation of an adduct with cytoplasmic leucyl-aminoacyl transfer RNA (tRNA) synthetase.

TargetActionsOrganism
ACytosolic leucyl-tRNA synthetase
inhibitor
Yeast
Additional Data Available
Adverse Effects

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Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Additional Data Available
Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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Absorption

7.5%. Subungual onychomycosis is difficult to treat due to the poorly perfused location of the infection in the nailbed. To be effective, a topical treatment must penetrate the nail plate and reach the site of infection at a concentration sufficient to exert anti-fungal activity. Tavaborole was shown to produce anti-fungal effects after 5 days of topical administration.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Tavaborole undergoes extensive metabolism. Metabolite profiling revealed trace levels of a sulfated-conjugate and a benzoic acid metabolite, consistent with the known biotransformation of tavaborole.

Route of elimination

Primarily renal.

Half life

28.5 hr

Clearance
Not Available
Toxicity

Tavaborole is generally well tolerated with most adverse events reported as mild and not related to treatment. Treatment related adverse events that occurred in >1 % of participants include application site exfoliation, application site erythema, and application site dermatitis, and ingrown toenail.

Affected organisms
  • Yeast and other Trichophyton or Microsporum fungi
  • Dermatophytic fungi including Trichophyton, Microsporum and Epidermophyton
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Toledo-Bahena ME, Bucko A, Ocampo-Candiani J, Herz-Ruelas ME, Jones TM, Jarratt MT, Pollak RA, Zane LT: The efficacy and safety of tavaborole, a novel, boron-based pharmaceutical agent: phase 2 studies conducted for the topical treatment of toenail onychomycosis. J Drugs Dermatol. 2014 Sep;13(9):1124-32. [PubMed:25226015]
  2. Markham A: Tavaborole: first global approval. Drugs. 2014 Sep;74(13):1555-8. doi: 10.1007/s40265-014-0276-7. [PubMed:25118637]
External Links
KEGG Drug
D10169
PubChem Compound
11499245
PubChem Substance
310264989
ChemSpider
9674047
BindingDB
50370987
ChEBI
77942
ChEMBL
CHEMBL443052
Wikipedia
Tavaborole
ATC Codes
D01AE24 — Tavaborole
FDA label
Download (603 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedOtherOnychomycosis1
2CompletedTreatmentDistal, Subungual Onychomycosis2
2CompletedTreatmentOnychomycosis5
3CompletedTreatmentOnychomycosis of Toenails2
4CompletedTreatmentOnychomycosis / Tinea Unguium1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
SolutionTopical43.5 mg/1mL
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7582621Yes2009-09-012027-11-26Us
US7767657No2010-08-032027-05-22Us
US9566289Yes2017-02-142026-08-16Us
US9549938Yes2017-01-242026-08-16Us
US9566290Yes2017-02-142026-08-16Us
US9572823Yes2017-02-212026-08-16Us
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

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Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility11.3 mg/mLALOGPS
logP1.51ALOGPS
logP2.24ChemAxon
logS-1.1ALOGPS
pKa (Strongest Acidic)8.91ChemAxon
pKa (Strongest Basic)-4.8ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area29.46 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity33.86 m3·mol-1ChemAxon
Polarizability14.21 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

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 aryl fluorides. These are organic compounds containing the acyl fluoride functional group.
Kingdom
Organic compounds
Super Class
Organohalogen compounds
Class
Aryl halides
Sub Class
Aryl fluorides
Direct Parent
Aryl fluorides
Alternative Parents
Benzenoids / Oxaborole derivatives / Boronic acid esters / Oxacyclic compounds / Organic metalloid salts / Organooxygen compounds / Organofluorides / Organoboron compounds / Hydrocarbon derivatives
Substituents
Benzenoid / Aryl fluoride / 1,2-oxaborole derivative / Boronic acid ester / Boronic acid derivative / Oxacycle / Organic metalloid salt / Organoheterocyclic compound / Organic oxygen compound / Hydrocarbon derivative
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
organofluorine compound, benzoxaborole (CHEBI:77942)

Targets

Kind
Protein
Organism
Yeast
Pharmacological action
Yes
Actions
Inhibitor
General Function
Leucine-trna ligase activity
Specific Function
Not Available
Gene Name
CDC60
Uniprot ID
Q9HGT2
Uniprot Name
Cytosolic leucyl-tRNA synthetase
Molecular Weight
125454.54 Da
References
  1. Toledo-Bahena ME, Bucko A, Ocampo-Candiani J, Herz-Ruelas ME, Jones TM, Jarratt MT, Pollak RA, Zane LT: The efficacy and safety of tavaborole, a novel, boron-based pharmaceutical agent: phase 2 studies conducted for the topical treatment of toenail onychomycosis. J Drugs Dermatol. 2014 Sep;13(9):1124-32. [PubMed:25226015]

Drug created on April 23, 2015 11:24 / Updated on May 01, 2019 10:49