AFOXOLANER

Details

Stereochemistry	RACEMIC
Molecular Formula	C26H17ClF9N3O3
Molecular Weight	625.87
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

FC(F)(F)CNC(=O)CNC(=O)C1=C2C=CC=CC2=C(C=C1)C3=NOC(C3)(C4=CC(=CC(Cl)=C4)C(F)(F)F)C(F)(F)F

InChI

InChIKey=OXDDDHGGRFRLEE-UHFFFAOYSA-N

InChI=1S/C26H17ClF9N3O3/c27-15-8-13(7-14(9-15)25(31,32)33)23(26(34,35)36)10-20(39-42-23)18-5-6-19(17-4-2-1-3-16(17)18)22(41)37-11-21(40)38-12-24(28,29)30/h1-9H,10-12H2,(H,37,41)(H,38,40)

HIDE SMILES / InChI

Molecular Formula	C26H17ClF9N3O3
Molecular Weight	625.87
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

Description

Afoxolaner (brand name NexGard) is a member of an isoxazoline class of compounds, which is used to kill adult fleas and is indicated for the treatment and prevention of flea infestations, and the treatment and control of Black-legged tick, American Dog tick, Lone Star tick, and Brown dog tick infestations in dogs and puppies. Afoxolaner is a member of the isoxazoline family, shown to bind at a binding site to inhibit insect and acarine ligand-gated chloride channels, in particular those gated by the neurotransmitter gamma-aminobutyric acid (GABA), thereby blocking pre- and post-synaptic transfer of chloride ions across cell membranes. Afoxolaner blocks native and expressed insect GABA-gated chloride channels with nanomolar potency. Prolonged afoxolaner-induced hyperexcitation results in uncontrolled activity of the central nervous system and death of insects and acarines.

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
insect and acarine GABA-gated chloride channels 1	Blocker 555

Conditions

Condition	Modality	Targets	Highest Phase	Product
Flea infestations 12	Curative		Approved 8,583	NEXGARD
Black-legged tick infestations 1	Curative		Approved 8,583	NEXGARD

PubMed

Show entries

Title	Date	PubMed
Afoxolaner against fleas: immediate efficacy and resultant mortality after short exposure on dogs.	2014	25148564
Discovery and mode of action of afoxolaner, a new isoxazoline parasiticide for dogs.	2014 Apr 2	24631502
Evaluation of the efficacy of afoxolaner against Haemaphysalis longicornis on dogs.	2014 Apr 2	24629429
Evaluation of the efficacy of monthly oral administration of afoxolaner plus milbemycin oxime (NexGard Spectra(®), Merial) in the prevention of adult Spirocerca lupi establishment in experimentally infected dogs.	2016 Aug 15	27514901

Showing 1 to 4 of 4 entries

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Patents

Sample Use Guides

In Vivo Use Guide

in veterinary: NexGard is given orally once a month, at the minimum dosage of 1.14 mg/lb (2.5 mg/kg). Dosing Schedule: Body Weight Afoxolaner Per Chewable (mg) Chewables Administered 4.0 to 10.0 lbs. 11.3 One 10.1 to 24.0 lbs. 28.3 One 24.1 to 60.0 lbs. 68 One 60.1 to 121.0 lbs. 136 One Over 121.0 lbs. Administer the appropriate combination of chewables

Route of Administration: Oral

In Vitro Use Guide

A dosage and time titration effect was clearly identified for fleas ingesting afoxolaner with mean efficacies of >95% recorded for fleas fed blood containing the compound at concentrations of 0.16, 0.08 and 0.02 μg/ml at the 24, 48 and 72 h observation points, respectively. There was only 1%, 2.3% and 2.3% mean mortality in the vehicle-treated control at the 24, 48 and 72 h observation points, respectively. Therefore, afoxolaner was judged to be highly active against fleas following ingestion in blood.