Identification

Name
Tavaborole
Accession Number
DB09041  (DB05058)
Type
Small Molecule
Groups
Approved
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
External IDs
AN 2690 / AN-2690 / AN2690
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
KerydinSolution43.5 mg/mLTopicalAnacor Pharmaceuticals, Inc.2014-07-072016-10-26Us
KerydinSolution43.5 mg/mLTopicalPharma Derm, A Division Of Fougera Pharmaceuticals Inc.2014-07-07Not applicableUs
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.

Structured Indications
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
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
DrugInteractionDrug group
AmlodipineThe risk or severity of adverse effects can be increased when Tavaborole is combined with Amlodipine.Approved
Amphotericin BThe therapeutic efficacy of Amphotericin B can be decreased when used in combination with Tavaborole.Approved, Investigational
AmrinoneThe risk or severity of adverse effects can be increased when Tavaborole is combined with Amrinone.Approved
AzelnidipineThe risk or severity of adverse effects can be increased when Tavaborole is combined with Azelnidipine.Approved, Investigational
AzimilideThe risk or severity of adverse effects can be increased when Tavaborole is combined with Azimilide.Investigational
BarnidipineThe risk or severity of adverse effects can be increased when Tavaborole is combined with Barnidipine.Approved
BencyclaneThe risk or severity of adverse effects can be increased when Tavaborole is combined with Bencyclane.Experimental
BenidipineThe risk or severity of adverse effects can be increased when Tavaborole is combined with Benidipine.Approved, Investigational
BepridilThe risk or severity of adverse effects can be increased when Tavaborole is combined with Bepridil.Approved, Withdrawn
BuspironeThe metabolism of Buspirone can be decreased when combined with Tavaborole.Approved, Investigational
BusulfanThe serum concentration of Busulfan can be increased when it is combined with Tavaborole.Approved, Investigational
CarboxyamidotriazoleThe risk or severity of adverse effects can be increased when Tavaborole is combined with Carboxyamidotriazole.Investigational
CaroverineThe risk or severity of adverse effects can be increased when Tavaborole is combined with Caroverine.Experimental
CilnidipineThe risk or severity of adverse effects can be increased when Tavaborole is combined with Cilnidipine.Approved, Investigational
CinnarizineThe risk or severity of adverse effects can be increased when Tavaborole is combined with Cinnarizine.Approved, Investigational
CisaprideThe serum concentration of Cisapride can be increased when it is combined with Tavaborole.Approved, Investigational, Withdrawn
ClevidipineThe risk or severity of adverse effects can be increased when Tavaborole is combined with Clevidipine.Approved
CyclosporineThe metabolism of Cyclosporine can be decreased when combined with Tavaborole.Approved, Investigational, Vet Approved
DarodipineThe risk or severity of adverse effects can be increased when Tavaborole is combined with Darodipine.Experimental
DidanosineDidanosine can cause a decrease in the absorption of Tavaborole resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
DiltiazemThe risk or severity of adverse effects can be increased when Tavaborole is combined with Diltiazem.Approved
DocetaxelThe metabolism of Docetaxel can be decreased when combined with Tavaborole.Approved, Investigational
DofetilideThe serum concentration of Dofetilide can be increased when it is combined with Tavaborole.Approved
DotarizineThe risk or severity of adverse effects can be increased when Tavaborole is combined with Dotarizine.Investigational
EfonidipineThe risk or severity of adverse effects can be increased when Tavaborole is combined with Efonidipine.Approved, Investigational
EperisoneThe risk or severity of adverse effects can be increased when Tavaborole is combined with Eperisone.Approved, Investigational
EtravirineThe serum concentration of Etravirine can be increased when it is combined with Tavaborole.Approved
FelodipineThe risk or severity of adverse effects can be increased when Tavaborole is combined with Felodipine.Approved, Investigational
FendilineThe risk or severity of adverse effects can be increased when Tavaborole is combined with Fendiline.Withdrawn
FlunarizineThe risk or severity of adverse effects can be increased when Tavaborole is combined with Flunarizine.Approved
FosphenytoinThe serum concentration of Tavaborole can be decreased when it is combined with Fosphenytoin.Approved
GabapentinThe risk or severity of adverse effects can be increased when Tavaborole is combined with Gabapentin.Approved, Investigational
GallopamilThe risk or severity of adverse effects can be increased when Tavaborole is combined with Gallopamil.Investigational
IsradipineThe risk or severity of adverse effects can be increased when Tavaborole is combined with Isradipine.Approved
LacidipineThe risk or severity of adverse effects can be increased when Tavaborole is combined with Lacidipine.Approved, Investigational
LamotrigineThe risk or severity of adverse effects can be increased when Tavaborole is combined with Lamotrigine.Approved, Investigational
LercanidipineThe risk or severity of adverse effects can be increased when Tavaborole is combined with Lercanidipine.Approved, Investigational
LidoflazineThe risk or severity of adverse effects can be increased when Tavaborole is combined with Lidoflazine.Experimental
LosartanThe metabolism of Losartan can be decreased when combined with Tavaborole.Approved
Magnesium SulfateThe risk or severity of adverse effects can be increased when Tavaborole is combined with Magnesium Sulfate.Approved, Vet Approved
ManidipineThe risk or severity of adverse effects can be increased when Tavaborole is combined with Manidipine.Approved, Investigational
MibefradilThe risk or severity of adverse effects can be increased when Tavaborole is combined with Mibefradil.Investigational, Withdrawn
NaftopidilThe risk or severity of adverse effects can be increased when Tavaborole is combined with Naftopidil.Investigational
NicardipineThe risk or severity of adverse effects can be increased when Tavaborole is combined with Nicardipine.Approved
NifedipineThe risk or severity of adverse effects can be increased when Tavaborole is combined with Nifedipine.Approved
NiguldipineThe risk or severity of adverse effects can be increased when Tavaborole is combined with Niguldipine.Experimental
NiludipineThe risk or severity of adverse effects can be increased when Tavaborole is combined with Niludipine.Experimental
NilvadipineThe risk or severity of adverse effects can be increased when Tavaborole is combined with Nilvadipine.Approved, Investigational
NimesulideThe risk or severity of adverse effects can be increased when Tavaborole is combined with Nimesulide.Approved, Investigational, Withdrawn
NimodipineThe risk or severity of adverse effects can be increased when Tavaborole is combined with Nimodipine.Approved
NisoldipineThe risk or severity of adverse effects can be increased when Tavaborole is combined with Nisoldipine.Approved
NitrendipineThe risk or severity of adverse effects can be increased when Tavaborole is combined with Nitrendipine.Approved, Investigational
OtiloniumThe risk or severity of adverse effects can be increased when Tavaborole is combined with Otilonium.Experimental, Investigational
PerhexilineThe risk or severity of adverse effects can be increased when Tavaborole is combined with Perhexiline.Approved, Investigational
PhenytoinThe serum concentration of Phenytoin can be increased when it is combined with Tavaborole.Approved, Vet Approved
PinaveriumThe risk or severity of adverse effects can be increased when Tavaborole is combined with Pinaverium.Approved
PregabalinThe risk or severity of adverse effects can be increased when Tavaborole is combined with Pregabalin.Approved, Illicit, Investigational
PrenylamineThe risk or severity of adverse effects can be increased when Tavaborole is combined with Prenylamine.Withdrawn
ProgesteroneThe absorption of Progesterone can be decreased when combined with Tavaborole.Approved, Vet Approved
QuinidineThe serum concentration of Quinidine can be increased when it is combined with Tavaborole.Approved
RanolazineThe serum concentration of Ranolazine can be increased when it is combined with Tavaborole.Approved, Investigational
RifabutinThe serum concentration of Rifabutin can be increased when it is combined with Tavaborole.Approved
RifampicinThe serum concentration of Rifampicin can be increased when it is combined with Tavaborole.Approved
RifapentineThe serum concentration of Rifapentine can be increased when it is combined with Tavaborole.Approved
RifaximinThe serum concentration of Rifaximin can be increased when it is combined with Tavaborole.Approved, Investigational
RisedronateThe risk or severity of adverse effects can be increased when Tavaborole is combined with Risedronate.Approved, Investigational
SolifenacinThe metabolism of Solifenacin can be decreased when combined with Tavaborole.Approved
SucralfateSucralfate can cause a decrease in the absorption of Tavaborole resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
SunitinibThe metabolism of Sunitinib can be decreased when combined with Tavaborole.Approved, Investigational
TacrolimusThe metabolism of Tacrolimus can be decreased when combined with Tavaborole.Approved, Investigational
TerodilineThe risk or severity of adverse effects can be increased when Tavaborole is combined with Terodiline.Experimental
TetrahydropalmatineThe risk or severity of adverse effects can be increased when Tavaborole is combined with Tetrahydropalmatine.Investigational
Tolfenamic AcidThe risk or severity of adverse effects can be increased when Tavaborole is combined with Tolfenamic Acid.Approved
TranilastThe risk or severity of adverse effects can be increased when Tavaborole is combined with Tranilast.Approved, Investigational
VerapamilThe risk or severity of adverse effects can be increased when Tavaborole is combined with Verapamil.Approved
VinpocetineThe risk or severity of adverse effects can be increased when Tavaborole is combined with Vinpocetine.Investigational
XylometazolineThe risk or severity of adverse effects can be increased when Tavaborole is combined with Xylometazoline.Approved
ZiconotideThe risk or severity of adverse effects can be increased when Tavaborole is combined with Ziconotide.Approved
ZolpidemThe serum concentration of Zolpidem can be increased when it is combined with Tavaborole.Approved
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
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Tavaborole
FDA label
Download (603 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedOtherOnychomycosis1
1, 2CompletedTreatmentOnychomycosis2
2CompletedTreatmentDistal, Subungual Onychomycosis2
2CompletedTreatmentOnychomycosis3
3CompletedTreatmentOnychomycosis of Toenails2

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
SolutionTopical43.5 mg/mL
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7582621No2007-05-262027-05-26Us
US7767657No2007-05-222027-05-22Us
US9566289No2006-02-162026-02-16Us
US9549938No2006-02-162026-02-16Us
US9566290No2006-02-162026-02-16Us
US9572823No2006-02-162026-02-16Us

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 December 01, 2017 16:12