Sarolaner
(Synonyms: 1-[5'-[(5S)-5-(3,5-二氯-4-氟苯基)-4,5-二氢-5-(三氟甲基)-3-异恶唑基]螺[氮杂环丁烷-3,1'(3'H)-异苯并呋喃]-1-基]-2-(甲基磺酰基)乙酮,PF-6450567) 目录号 : GC34774
An isoxazoline ectoparasiticide
Cas No.:1398609-39-6
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Sarolaner is an isoxazoline ectoparasiticide.1 It inhibits GABA-induced chloride currents in CHO-K1 cells expressing either the gene for susceptible C. felis flea resistance-to-dieldrin subunits containing alanine at residue 285 (CfRDL-A285; IC50 = 135 nM) or the gene for CfRDL subunits containing the alanine-to-serine resistance mutation (CfRDL-S285; IC50 = 136 nM). It induces mortality in C. felis fleas (LC80 = 0.3 ?g/ml) and O. turicata soft ticks (LC100 = 0.003 ?g/ml). Sarolaner (2.5 mg/kg) eliminates live C. felis fleas, as well as R. sanguineus, I. ricinus, and D. reticulatus ticks, on dogs after 48 hours and reduces the number of fleas and ticks for at least 35 days. Formulations containing sarolaner have been used in the treatment and control of flea and tick infestations in dogs.
1.McTier, T.L., Chubb, N., Curtis, M.P., et al.Discovery of sarolaner: A novel, orally administered, broad-spectrum, isoxazoline ectoparasiticide for dogsVet. Parasitol.2223-11(2016)
| Cas No. | 1398609-39-6 | SDF | |
| 别名 | 1-[5'-[(5S)-5-(3,5-二氯-4-氟苯基)-4,5-二氢-5-(三氟甲基)-3-异恶唑基]螺[氮杂环丁烷-3,1'(3'H)-异苯并呋喃]-1-基]-2-(甲基磺酰基)乙酮,PF-6450567 | ||
| Canonical SMILES | O=S(CC(N1CC2(OCC3=C2C=CC(C4=NO[C@](C(F)(F)F)(C5=CC(Cl)=C(F)C(Cl)=C5)C4)=C3)C1)=O)(C)=O | ||
| 分子式 | C23H18Cl2F4N2O5S | 分子量 | 581.36 |
| 溶解度 | DMSO : 150 mg/mL (258.02 mM);Water : < 0.1 mg/mL (insoluble) | 储存条件 | Store at 4°C, sealed storage, away from moisture |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.7201 mL | 8.6005 mL | 17.201 mL |
| 5 mM | 0.344 mL | 1.7201 mL | 3.4402 mL |
| 10 mM | 0.172 mL | 0.8601 mL | 1.7201 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Efficacy and safety of Sarolaner (Simparica®) in the treatment and control of naturally occurring flea infestations in dogs presented as veterinary patients in Australia
Parasit Vectors 2017 Aug 16;10(1):387.PMID:28814332DOI:10.1186/s13071-017-2321-3.
Background: The efficacy and safety of a novel isoxazoline compound, Sarolaner (Simparica®, Zoetis) and spinosad (Comfortis®, Elanco) as a positive control were evaluated for the treatment and control of natural flea infestations on dogs in two randomised, blinded, multi-centric clinical trials conducted in 11 veterinary clinics in northeastern and southeastern states of Australia. Methods: A total of 162 client-owned dogs (80 in northern study and 82 in southern study) from 105 households were enrolled. Each household was randomly allocated to receive either Sarolaner (Simparica®, Zoetis) or spinosad (Comfortis®, Elanco). Dogs were dosed on Days 0, 30 and 60 and physical examinations and flea counts were conducted on Days 0, 14, 30, 60 and 90. Efficacy assessments were based on the percentage reduction in live flea counts post-treatment compared to Day 0. Results: In the northern study, at enrolment, primary dogs had flea counts ranging from 5 to 772. At the first efficacy assessment on Day 14, Sarolaner resulted in 99.3% mean reduction in live flea counts relative to Day 0, compared to 94.6% in the spinosad group. On Day 30, the sarolaner-treated group had mean efficacy of 99.2% compared to 95.7% in the spinosad-treated group, and on days 60 and 90, both groups had mean efficacies of ≥ 98.8%. In the southern study, at enrolment, primary dogs had flea counts ranging from 5 to 156. Both Sarolaner and spinosad resulted in ≥ 96.7% mean reduction in live flea counts on Day 14. On Day 30, the sarolaner-treated group had mean efficacy of 99.5% compared to 89.7% in the spinosad-treated group, and on days 60 and 90, both groups had mean efficacies of ≥ 98.6%. No treatment-related adverse events were observed in either study. Conclusions: A single monthly dose of Sarolaner (Simparica®) administered orally at 2-4 mg/kg for three consecutive months was well tolerated and provided excellent efficacy against natural infestations of fleas under a range of Australian field conditions including different climatic and housing conditions. Similar efficacy was observed with spinosad (Comfortis®) after the second and third monthly treatments.
Discovery of Sarolaner: A novel, orally administered, broad-spectrum, isoxazoline ectoparasiticide for dogs
Vet Parasitol 2016 May 30;222:3-11.PMID:26961590DOI:10.1016/j.vetpar.2016.02.019.
The novel isoxazoline ectoparasiticide, Sarolaner, was identified during a lead optimization program for an orally-active compound with efficacy against fleas and ticks on dogs. The aim of the discovery program was to identify a novel isoxazoline specifically for use in companion animals, beginning with de novo synthesis in the Zoetis research laboratories. The Sarolaner molecule has unique structural features important for its potency and pharmacokinetic (PK) properties, including spiroazetidine and sulfone moieties. The flea and tick activity resides in the chirally pure S-enantiomer, which was purified to alleviate potential off-target effects from the inactive enantiomer. The mechanism of action was established in electrophysiology assays using CHO-K1 cell lines stably expressing cat flea (Ctenocephalides felis) RDL (resistance-to-dieldrin) genes for assessment of GABA-gated chloride channel (GABACls) pharmacology. As expected, Sarolaner inhibited GABA-elicited currents at both susceptible (CfRDL-A285) and resistant (CfRDL-S285) flea GABACls with similar potency. Initial whole organism screening was conducted in vitro using a blood feeding assay against C. felis. Compounds which demonstrated robust activity in the flea feed assay were subsequently tested in an in vitro ingestion assay against the soft tick, Ornithodoros turicata. Efficacious compounds which were confirmed safe in rodents at doses up to 30mg/kg were progressed to safety, PK and efficacy studies in dogs. In vitro Sarolaner demonstrated an LC80 of 0.3μg/mL against C. felis and an LC100 of 0.003μg/mL against O. turicata. In a head-to-head comparative in vitro assay with both afoxolaner and fluralaner, Sarolaner demonstrated superior flea and tick potency. In exploratory safety studies in dogs, Sarolaner demonstrated safety in dogs≥8 weeks of age upon repeated monthly dosing at up to 20mg/kg. Sarolaner was rapidly and well absorbed following oral dosing. Time to maximum plasma concentration occurred within the first day post-dose. Bioavailability for Sarolaner was calculated at >85% and the compound was highly protein bound (>99.9%). The half-life for Sarolaner was calculated at 11-12 days. Sarolaner plasma concentrations indicated dose proportionality over the range 1.25-5mg/kg, and these same doses provided robust efficacy (>99%) for ≥35days against both fleas (C. felis) and multiple species of ticks (Rhipicephalus sanguineus, Ixodes ricinus and Dermacentor reticulatus) after oral administration to dogs. As a result of these exploratory investigations, Sarolaner was progressed for development as an oral monthly dose for treatment and control of fleas and ticks on dogs.
Efficacy of Oral Sarolaner for the Treatment of Feline Otodectic Mange
Pathogens 2021 Mar 15;10(3):341.PMID:33804037DOI:10.3390/pathogens10030341.
Otodectes cynotis is a mite with a cosmopolitan distribution that is the primary agent for the development of otitis externa in feline species. The aim of this study was to evaluate the efficacy of the oral administration of Sarolaner for the treatment of feline otodectic mange. We used 20 adult cats of both sexes that were naturally infested with O. cynotis. The mite infestation scoring was performed by video-otoscopy before treatment. The cats were randomized according to the infestation score and divided into two groups (treated and control). The treated group underwent oral administration of Sarolaner in a single dose of 2-4 mg/kg. The evaluations were performed by video-otoscopy to evaluate the reduction of infestation score 2, 4, 6, 24 and 48 h and 7, 14, 21 and 28 days after medication. At the end of the study, the cats were sedated to enable the recovery of live and dead mites to determine efficacy. No adverse effects or laboratory changes were observed in these cats. Sarolaner showed 100% efficacy 48 h after treatment. Based on the results, a single oral dose of Sarolaner was effective in controlling otodectic mange in naturally infested cats.
Efficacy of Sarolaner (Simparica®) against induced infestations of Haemaphysalis longicornis on dogs
Parasit Vectors 2019 Oct 30;12(1):509.PMID:31666109DOI:10.1186/s13071-019-3765-4.
Background: Haemaphysalis longicornis is the major tick affecting dogs in most of the East Asia/Pacific region and has recently been detected in a number of areas of the USA. This tick is a vector for a number of pathogens of dogs, other mammals and humans. In this study, the efficacy of a single oral administration of Sarolaner (Simparica®, Zoetis) at the minimum label dosage (2 mg/kg) was evaluated against an existing infestation of H. longicornis and subsequent weekly reinfestations for 5 weeks after treatment. Methods: Sixteen dogs were ranked on pretreatment tick counts and randomly allocated to treatment on Day 0 with Sarolaner at 2 mg/kg or a placebo. The dogs were infested with H. longicornis nymphs on Days - 2, 5, 12, 19, 26 and 33. Efficacy was determined at 48 hours after treatment and subsequent re-infestations based on live tick counts relative to placebo-treated dogs. Results: There were no adverse reactions to treatment. A single dose of Sarolaner provided 100% efficacy on Days 2, 7, 14 and 21; and ≥ 97.4% efficacy on Days 28 and 35. Considering only attached, live ticks, efficacy was 100% for the entire 35 days of the study. Geometric mean live tick counts for Sarolaner were significantly lower than those for placebo on all days (11.62 ≤ t(df) ≤ 59.99, where 13.0 ≤ df ≤ 14.1, P < 0.0001). Conclusions: In this study, a single oral administration of Sarolaner at 2 mg/kg provided 100% efficacy against an existing infestation of H. longicornis nymphs and ≥ 97.4% efficacy (100% against attached ticks) against weekly reinfestation for at least 35 days after treatment.
Efficacy of oral Sarolaner against Lynxacarus radovskyi in naturally infested cats
Vet Dermatol 2020 Oct;31(5):355-e92.PMID:32497276DOI:10.1111/vde.12857.
Background: Lynxacarus radovskyi is a fur mite of cats. Several classes of ectoparasiticides have shown success for treatment, including an isoxazoline. Objectives: To evaluate the efficacy of a single oral dose of Sarolaner for the treatment of L. radovskyi mites in naturally infested cats. Animals: Fourteen adult cats (six males and eight females), naturally infested with L. radovskyi. Methods and materials: Animals were randomized according to sex and average pretreatment mite count. The cats were assigned to two groups of seven cats each. The treated group received one 10 mg Sarolaner tablet, corresponding to a dose of 2-4 mg/kg body weight, and the control group received no treatment. From each cat, three trichograms consisting of approximately 50 hairs each were collected from the dorsal neck, lateral thigh and perineum/tail region (total of nine samples per cat). The severity of infestation was scored on a scale of 0 (no parasites) to 4 (>50 mites) at baseline and days 7, 15, 30, 45 and 60 post-treatment. Efficacy was compared between the treatment and control groups using the arithmetic mean reduction of the mite score; results were analysed using the Kruskal-Wallis test followed by the Student-Newtman-Keuls test, with significance set at P < 5%. Results: The efficacy of oral Sarolaner was >95% at Day 30 post-treatment. Statistical differences were first observed between the means of the control and treated groups 15 days post-treatment. Conclusion: A single oral dose of Sarolaner effectively eliminated L. radovskyi in most cats.