Tradipitant (VLY-686)
(Synonyms: VLY-686; LY686017) 目录号 : GC33735
Tradipitant (VLY-686) (VLY-686) 是一种神经激肽-1 (NK-1) 拮抗剂。
Cas No.:622370-35-8
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cell experiment: | Brains from male, Hartley guinea pigs (350 to 400 g) are removed, rinsed for 5 to 15 min in cold PBS, patted dry with a paper towel and frozen on aluminum foil lined with parafilm placed on dry ice. Once frozen, the brains are stored at -80°C until they are sectioned using a cryostat set at a thickness of 12 μm. The tissue sections are thaw mounted onto chrome alum/gelatin coated slides and allowed to air dry for 5 to 20 min before being frozen again. To assessthe binding of Tradipitant ([3H]-LY686017) to sections, the slides are preincubated for 30 min in modified Kreb’s phosphate buffer followed by an incubation in the same buffer containing 0.05% bacitracin, 0.4% BSA and various concentrations of Tradipitant. Rinse time, incubation time and saturation binding are determined using sections through the caudate nucleus[1]. |
Animal experiment: | Male, Hartley guinea pigs (550 to 650 g) are used. Guinea pigs are singly housed in cages for 2 to 4 days before being used in an experiment. On the day of the experiment, the catheters are flushed with heparinized 0.9% saline and, if the catheter is clear, the animal received 25 microCi of Tradipitant ([3H]-LY686017) in saline for time course and compound displacement studies (n=4 to 6/group) and 100 microCi for autoradiography studies (n=5). The catheter line is cleared of radioactivity by again flushing the line with 0.5 mL heparinized saline. The end of the catheter is subsequently plugged using the original steel wire plug. Based on data from initial time course experiments, the animals are sacrificed by rapid decapitation 2 h post-jugular injection for compound displacement and autoradiography studies[1]. |
References: [1]. Gackenheimer SL, et al. In vitro and ex vivo autoradiography of the NK-1 antagonist [3H]-LY686017 in Guinea pig brain. Neuropeptides. 2011 Apr;45(2):157-64. | |
Tradipitant is a neurokinin-1 (NK-1) antagonist.
Results reveal that Tradipitant ([3H]-LY686017) bind to sections of guinea pig brain with a distribution similar to that previously reported for NK-1 receptors. Areas with the highest density are the accessory olfactory nucleus, anteroventral thalamic nucleus, paraventricular hypothalamic nucleus central amygdaloid nucleus (lateral) and the medial amygdaloid nucleus (anterodorsal)[1].
Autoradiography experiments reveal that intravenously administered Tradipitant ([3H]-LY686017) localizes in the guinea pig brain and has a distribution similar to that described for the NK-1 receptor using agonist or antagonist radioligands[1].
[1]. Gackenheimer SL, et al. In vitro and ex vivo autoradiography of the NK-1 antagonist [³H]-LY686017 in Guinea pig brain. Neuropeptides. 2011 Apr;45(2):157-64.
| Cas No. | 622370-35-8 | SDF | |
| 别名 | VLY-686; LY686017 | ||
| Canonical SMILES | O=C(C1=CC=CN=C1C2=C(C3=CC=NC=C3)N(CC4=CC(C(F)(F)F)=CC(C(F)(F)F)=C4)N=N2)C5=CC=CC=C5Cl | ||
| 分子式 | C28H16ClF6N5O | 分子量 | 587.9 |
| 溶解度 | DMSO: 100 mg/mL (170.10 mM) | 储存条件 | Store at -20°C |
| 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。 |
||
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 1.701 mL | 8.5048 mL | 17.0097 mL |
| 5 mM | 0.3402 mL | 1.701 mL | 3.4019 mL |
| 10 mM | 0.1701 mL | 0.8505 mL | 1.701 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。
Treatments for Childhood Atopic Dermatitis: an Update on Emerging Therapies
Clin Rev Allergy Immunol 2021 Oct;61(2):114-127.PMID:32607924DOI:10.1007/s12016-020-08799-1.
Atopic dermatitis (AD) is generally considered a T helper type 2-dominated disease. Pediatric AD is usually less severe than adult AD, but it may present as moderate to severe lesions that are inadequately managed by current modalities including emollients/moisturizers, topical corticosteroids (TCSs), topical calcineurin inhibitors (TCIs), and even systemic immunosuppressants (such as cyclosporine, azathioprine, methotrexate, and mycophenolate mofetil). In addition, systemic immunosuppressants are often not recommended for childhood AD by the current guidelines due to their toxicities. Therefore, there is still an unmet need for a safe and effective long-term therapy for pediatric AD patients whose disease is inadequately controlled or who are intolerant to current treatments. The emerging therapeutics for AD focuses on intervening in the inflammatory pathway by targeting specific cytokines/chemokines or their receptors. Monoclonal antibodies against immunoglobulin E (IgE), interleukin (IL)-4 receptor subunit α, IL-5, IL-13, IL-31 receptor subunit α, IL-33, and thymic stromal lymphopoietin (TSLP) have been evaluated clinically for AD. Encouraging results have been reported for many of the biologics, of which the most exciting is dupilumab. Other emerging systemic therapies include small molecules such as baricitinib, abrocitinib, upadacitinib, and Tradipitant. Several novel topical agents are under clinical investigation for the treatment of AD, including topical phosphodiesterase 4 (PDE4) inhibitors, Janus kinase (JAK) inhibitors, aryl hydrocarbon receptor (AhR) modulating agents, and transient receptor potential vanilloid subfamily member 1 (TRPV1) antagonists. Accompanied by thorough characterization of different phenotype and endotype subsets, the application of precision medicine could provide new prospects for the optimal treatment of AD.
Efficacy and Safety of Tradipitant in Patients With Diabetic and Idiopathic Gastroparesis in a Randomized, Placebo-Controlled Trial
Gastroenterology 2021 Jan;160(1):76-87.e4.PMID:32693185DOI:10.1053/j.gastro.2020.07.029.
Background & aims: Treatments are needed for gastroparesis; antagonists of tachykinin receptor 1 (TACR1, also called NK1R) can reduce symptoms of nausea and vomiting. We investigated the safety and efficacy of Tradipitant, an antagonist of NK1R, in patients with idiopathic or diabetic gastroparesis. Methods: We performed a double-blind trial of 152 adults with gastroparesis at 47 sites in the United States from November 2016 through December 2018. Participants were randomly assigned to groups given oral Tradipitant 85 mg (n = 77) or placebo (n = 75) twice daily for 4 weeks. Symptoms were assessed by a daily symptom dairy, Gastroparesis Cardinal Symptom Index scores, and other patient-reported questionnaires. The primary outcome from the intent-to-treat analysis was change from baseline to week 4 in average nausea severity, measured by the Gastroparesis Core Symptom Daily Diary. Results: Patients receiving Tradipitant had a significant decrease in nausea score (reduction of 1.2) at week 4 compared with placebo (reduction of 0.7) (P = .0099) and a significant increase in of nausea-free days at week 4 (28.8% increase on Tradipitant vs 15.0% on placebo; P = .0160). Patients with nausea and vomiting at baseline (n = 101) had an even greater decrease in nausea in when given Tradipitant (reduction of 1.4) compared with those given placebo (reduction of 0.4) (P < .0001), as well as an increase in nausea-free days at week 4 (32.3% improvement on Tradipitant vs 7.6% on placebo; P = .0003). The average nausea score was 1 or less at week 4 in 32.9% of patients given Tradipitant compared with 11.8% of patients given placebo (P = .0013). A greater than 1-point improvement in Gastroparesis Cardinal Symptom Index score was observed in 46.6% of patients given Tradipitant compared with 23.5% of patients given placebo (P = .0053). Conclusions: Tradipitant resulted in statistically and clinically meaningful improvements in nausea and reduced vomiting, compared with placebo, in patients with idiopathic or diabetic gastroparesis. ClinicalTrials.gov, Number: NCT02970968.
Evaluation of Tradipitant, a selective NK1 antagonist, on response to oxycodone in humans
Psychopharmacology (Berl) 2021 Jul;238(7):1857-1866.PMID:33988725DOI:10.1007/s00213-021-05814-x.
Rationale: Preclinical studies demonstrate that the NK1 receptor is involved in opioid reinforcement and withdrawal expression. Few studies have examined the impact of treatment with NK1 antagonists on opioid response in humans. Objective: To explore the potential for a selective NK1 antagonist, Tradipitant, to attenuate the abuse liability and reinforcing and analgesic effects of oxycodone in opioid-experienced individuals. Methods: Participants with recreational opioid use, but without opioid physical dependence, were enrolled as inpatients for ~6 weeks (n = 8). A within-subject, double-blind, randomized, placebo-controlled, crossover design was employed. The pharmacodynamic response to intranasal oxycodone across a range of doses (0 to 30 mg) was examined during two counterbalanced maintenance periods (Tradipitant 0 or 85 mg/bid). Oxycodone self-administration was assessed with a modified progressive ratio procedure, and analgesia was assessed with the cold pressor test. Results: Oxycodone produced significant and dose-related increases on a broad array of prototypic opioid measures, including subjective ratings related to abuse liability (e.g., liking) and physiological outcomes (i.e., expired CO2). Oxycodone self-administration increased with increasing dose, as did analgesia. Tradipitant largely did not alter any of these effects of oxycodone, with the exception of producing a reduction in ratings of desire for opioids. Conclusions: Given that the vast majority of oxycodone effects were unchanged by Tradipitant, these data do not provide support for the utility of NK1 antagonists as a potential treatment for opioid use disorder.
Tradipitant in the Treatment of Motion Sickness: A Randomized, Double-Blind, Placebo-Controlled Study
Front Neurol 2020 Sep 29;11:563373.PMID:33117260DOI:10.3389/fneur.2020.563373.
Introduction: Novel therapies are needed for the treatment of motion sickness given the inadequate relief and bothersome and dangerous adverse effects of currently approved therapies. Neurokinin-1 (NK1) receptor antagonists have the potential to be effective in improving the symptoms of motion sickness, given the involvement of Substance P in nauseogenic and emetic pathways and the expression of NK1 receptors in the gastrointestinal system. Here we evaluated the efficacy of Tradipitant, a novel NK1 receptor antagonist, in preventing motion sickness in variable sea conditions. Methods: A total of 126 adults participated in the Motion Sifnos study. Groups of participants were assigned to one of seven boat trips lasting ~4 h on the Pacific Ocean. Participants were randomized 1:1 to Tradipitant 170 mg or placebo and completed the Motion Sickness Severity Scale (MSSS) every 30 min, in addition to other assessments. Severity of motion sickness was assessed with the incidence of vomiting and the MSSS. Results: Participants on Tradipitant had a significantly lower incidence of vomiting as compared to those on placebo across all boat trips (Tradipitant = 17.5%, placebo = 39.7%, p = 0.0039). For trips exposed to rough sea conditions, the difference in the incidence of vomiting between the groups was more dramatic (Tradipitant = 15.79%, placebo = 72.22%, p = 0.0009). Across these trips, motion sickness symptoms were significantly lower in the Tradipitant group compared to the placebo group (Tradipitant = 3.19, placebo = 4.57, p = 0.0235). Discussion: Tradipitant has the potential to be an effective therapy for the prevention of vomiting and treatment of nausea in people with motion sickness.
Clinical trial: a single-centre, randomised, controlled trial of Tradipitant on satiation, gastric functions, and serum drug levels in healthy volunteers
Aliment Pharmacol Ther 2022 Jul;56(2):224-230.PMID:35644931DOI:10.1111/apt.17065.
Background: Tradipitant, an NK1 receptor antagonist, improved symptoms in patients with gastroparesis. It is unclear whether these effects are mediated centrally (e.g., vomiting centre) or on gastric functions. As a class, NK1 antagonists may retard gastric emptying (GE) or increase fasting and postprandial gastric volumes (GV). Aim: To evaluate the effects of Tradipitant relative to placebo on gastric motor functions, satiation, postprandial symptoms, and pharmacokinetics. Methods: We conducted a randomised, double-blind, placebo-controlled, single-centre study of Tradipitant 85 mg or matching placebo b.i.d. for 9 consecutive days in 24 healthy volunteers. During the last 2 days of treatment, participants underwent scintigraphic measurements of GE of 320 kcal egg meal, fasting and postprandial GV by SPECT, and satiation by nutrient drink ingested to maximum tolerated volume (MTV) and symptoms 30 min later. Treatments were compared by Wilcoxon rank sum test. The study had 80% power to detect group differences of 23.6% in GV and 29.2% in GE T1/2 . Results: The two groups of healthy participants were well balanced based on demographic features, age, and BMI. There were nonsignificant positive correlations between blood levels of Tradipitant and accommodation GV and GE at 4 h. There were no significant effects of Tradipitant, 85 mg b.i.d. for 9 days compared to placebo on GE, GV, satiation, or symptoms 30 min after MTV. Conclusion: Tradipitant, 85 mg b.i.d., does not significantly affect gastric motor functions (GV or GE). Importantly, there was no retardation of GE by Tradipitant, which is important in relation to its potential use in patients with gastroparesis. Clinic trials registry: ClinicalTrials.gov #NCT04849559.