Identification

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
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.

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
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
AgmatineThe therapeutic efficacy of Tavaborole can be increased when used in combination with Agmatine.Experimental, Investigational
AmiodaroneThe therapeutic efficacy of Tavaborole can be increased when used in combination with Amiodarone.Approved, Investigational
AmlodipineThe therapeutic efficacy of Tavaborole can be increased when used in combination with Amlodipine.Approved
Amphotericin BThe therapeutic efficacy of Amphotericin B can be decreased when used in combination with Tavaborole.Approved, Investigational
AmrinoneThe therapeutic efficacy of Tavaborole can be increased when used in combination with Amrinone.Approved
AranidipineThe therapeutic efficacy of Tavaborole can be increased when used in combination with Aranidipine.Approved, Investigational
AzelnidipineThe therapeutic efficacy of Tavaborole can be increased when used in combination with Azelnidipine.Approved, Investigational
AzimilideThe therapeutic efficacy of Tavaborole can be increased when used in combination with Azimilide.Investigational
BarnidipineThe therapeutic efficacy of Tavaborole can be increased when used in combination with Barnidipine.Approved
BencyclaneThe therapeutic efficacy of Tavaborole can be increased when used in combination with Bencyclane.Experimental
BenidipineThe therapeutic efficacy of Tavaborole can be increased when used in combination with Benidipine.Approved, Investigational
BepridilThe therapeutic efficacy of Tavaborole can be increased when used in combination with Bepridil.Approved, Withdrawn
BioallethrinThe therapeutic efficacy of Tavaborole can be increased when used in combination with Bioallethrin.Approved, Experimental
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 therapeutic efficacy of Tavaborole can be increased when used in combination with Carboxyamidotriazole.Investigational
CaroverineThe therapeutic efficacy of Tavaborole can be increased when used in combination with Caroverine.Experimental
CilnidipineThe therapeutic efficacy of Tavaborole can be increased when used in combination with Cilnidipine.Approved, Investigational
CinnarizineThe therapeutic efficacy of Tavaborole can be increased when used in combination with Cinnarizine.Approved, Investigational
CisaprideThe serum concentration of Cisapride can be increased when it is combined with Tavaborole.Approved, Investigational, Withdrawn
ClevidipineThe therapeutic efficacy of Tavaborole can be increased when used in combination with Clevidipine.Approved, Investigational
CyclandelateThe therapeutic efficacy of Tavaborole can be increased when used in combination with Cyclandelate.Approved
CyclosporineThe metabolism of Cyclosporine can be decreased when combined with Tavaborole.Approved, Investigational, Vet Approved
DarodipineThe therapeutic efficacy of Tavaborole can be increased when used in combination 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 therapeutic efficacy of Tavaborole can be increased when used in combination with Diltiazem.Approved, Investigational
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, Investigational
DotarizineThe therapeutic efficacy of Tavaborole can be increased when used in combination with Dotarizine.Investigational
EfonidipineThe therapeutic efficacy of Tavaborole can be increased when used in combination with Efonidipine.Approved, Investigational
EperisoneThe therapeutic efficacy of Tavaborole can be increased when used in combination with Eperisone.Approved, Investigational
EthosuximideThe therapeutic efficacy of Tavaborole can be increased when used in combination with Ethosuximide.Approved
EtravirineThe serum concentration of Etravirine can be increased when it is combined with Tavaborole.Approved
FelodipineThe therapeutic efficacy of Tavaborole can be increased when used in combination with Felodipine.Approved, Investigational
FendilineThe therapeutic efficacy of Tavaborole can be increased when used in combination with Fendiline.Withdrawn
Fish oilThe therapeutic efficacy of Tavaborole can be increased when used in combination with Fish oil.Approved, Nutraceutical
FlunarizineThe therapeutic efficacy of Tavaborole can be increased when used in combination with Flunarizine.Approved
FluspirileneThe therapeutic efficacy of Tavaborole can be increased when used in combination with Fluspirilene.Approved, Investigational
FosphenytoinThe serum concentration of Tavaborole can be decreased when it is combined with Fosphenytoin.Approved, Investigational
GabapentinThe therapeutic efficacy of Tavaborole can be increased when used in combination with Gabapentin.Approved, Investigational
GallopamilThe therapeutic efficacy of Tavaborole can be increased when used in combination with Gallopamil.Investigational
IsradipineThe therapeutic efficacy of Tavaborole can be increased when used in combination with Isradipine.Approved, Investigational
LacidipineThe therapeutic efficacy of Tavaborole can be increased when used in combination with Lacidipine.Approved, Investigational
LamotrigineThe therapeutic efficacy of Tavaborole can be increased when used in combination with Lamotrigine.Approved, Investigational
LercanidipineThe therapeutic efficacy of Tavaborole can be increased when used in combination with Lercanidipine.Approved, Investigational
LevetiracetamThe therapeutic efficacy of Tavaborole can be increased when used in combination with Levetiracetam.Approved, Investigational
LidoflazineThe therapeutic efficacy of Tavaborole can be increased when used in combination with Lidoflazine.Experimental
LoperamideThe therapeutic efficacy of Tavaborole can be increased when used in combination with Loperamide.Approved
LosartanThe metabolism of Losartan can be decreased when combined with Tavaborole.Approved
Magnesium sulfateThe therapeutic efficacy of Tavaborole can be increased when used in combination with Magnesium sulfate.Approved, Investigational, Vet Approved
ManidipineThe therapeutic efficacy of Tavaborole can be increased when used in combination with Manidipine.Approved, Investigational
MentholThe therapeutic efficacy of Tavaborole can be increased when used in combination with Menthol.Approved
MethsuximideThe therapeutic efficacy of Tavaborole can be increased when used in combination with Methsuximide.Approved
MibefradilThe therapeutic efficacy of Tavaborole can be increased when used in combination with Mibefradil.Investigational, Withdrawn
NaftopidilThe therapeutic efficacy of Tavaborole can be increased when used in combination with Naftopidil.Investigational
NicardipineThe therapeutic efficacy of Tavaborole can be increased when used in combination with Nicardipine.Approved, Investigational
NifedipineThe therapeutic efficacy of Tavaborole can be increased when used in combination with Nifedipine.Approved
NiguldipineThe therapeutic efficacy of Tavaborole can be increased when used in combination with Niguldipine.Experimental
NiludipineThe therapeutic efficacy of Tavaborole can be increased when used in combination with Niludipine.Experimental
NilvadipineThe therapeutic efficacy of Tavaborole can be increased when used in combination with Nilvadipine.Approved, Investigational
NimesulideThe therapeutic efficacy of Tavaborole can be increased when used in combination with Nimesulide.Approved, Investigational, Withdrawn
NimodipineThe therapeutic efficacy of Tavaborole can be increased when used in combination with Nimodipine.Approved, Investigational
NisoldipineThe therapeutic efficacy of Tavaborole can be increased when used in combination with Nisoldipine.Approved
NitrendipineThe therapeutic efficacy of Tavaborole can be increased when used in combination with Nitrendipine.Approved, Investigational
NylidrinThe therapeutic efficacy of Tavaborole can be increased when used in combination with Nylidrin.Approved
OtiloniumThe therapeutic efficacy of Tavaborole can be increased when used in combination with Otilonium.Experimental, Investigational
PhenytoinThe serum concentration of Phenytoin can be increased when it is combined with Tavaborole.Approved, Vet Approved
PinaveriumThe therapeutic efficacy of Tavaborole can be increased when used in combination with Pinaverium.Approved
PrenylamineThe therapeutic efficacy of Tavaborole can be increased when used in combination 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, Investigational
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, Investigational
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, Investigational
RifaximinThe serum concentration of Rifaximin can be increased when it is combined with Tavaborole.Approved, Investigational
SeletracetamThe therapeutic efficacy of Tavaborole can be increased when used in combination with Seletracetam.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 therapeutic efficacy of Tavaborole can be increased when used in combination with Terodiline.Experimental
TetrahydropalmatineThe therapeutic efficacy of Tavaborole can be increased when used in combination with Tetrahydropalmatine.Investigational
Tolfenamic AcidThe therapeutic efficacy of Tavaborole can be increased when used in combination with Tolfenamic Acid.Approved, Investigational
TranilastThe therapeutic efficacy of Tavaborole can be increased when used in combination with Tranilast.Approved, Investigational
TrimebutineThe therapeutic efficacy of Tavaborole can be increased when used in combination with Trimebutine.Approved
TrimethadioneThe therapeutic efficacy of Tavaborole can be increased when used in combination with Trimethadione.Approved
VerapamilThe therapeutic efficacy of Tavaborole can be increased when used in combination with Verapamil.Approved
VinpocetineThe therapeutic efficacy of Tavaborole can be increased when used in combination with Vinpocetine.Investigational
WIN 55212-2The therapeutic efficacy of Tavaborole can be increased when used in combination with WIN 55212-2.Experimental
ZiconotideThe therapeutic efficacy of Tavaborole can be increased when used in combination with Ziconotide.Approved
ZolpidemThe serum concentration of Zolpidem can be increased when it is combined with Tavaborole.Approved
ZonisamideThe therapeutic efficacy of Tavaborole can be increased when used in combination with Zonisamide.Approved, Investigational
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
2CompletedTreatmentDistal, Subungual Onychomycosis2
2CompletedTreatmentOnychomycosis5
3CompletedTreatmentOnychomycosis of Toenails2
4CompletedTreatmentOnychomycosis / Tinea Unguium1

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 June 02, 2018 08:15