Timapiprant
(Synonyms: [5-氟-2-甲基-3-(喹啉-2-基甲基)吲哚-1-基]乙酸,OC000459) 目录号 : GC37794
A potent, selective DP2 antagonist
Cas No.:851723-84-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
OC000459 is a potent, selective DP2 antagonist that displaces [3H]prostaglandin D2 ([3H]PGD2) from human recombinant DP2 receptors (Ki = 13 nM), rat recombinant DP2 receptors (Ki = 3 nM), and human native DP2 (Ki = 4 nM; Th2 cell membranes) without interfering with the ligand binding properties of other prostanoid receptors, including PGE1–4, DP1, TP, PGI2, and PGF.1 OC000459 inhibits chemotaxis and cytokine production of human Th2 lymphocytes with IC50 values of 28 and 19 nM, respectively, and competitively antagonizes eosinophil shape change responses induced by PGD2 in both isolated human leukocytes (pKB = 7.9) and human whole blood (pKB = 7.5).1 OC000459 was shown to inhibit blood eosinophilia in rats induced by 13,14-
1.Pettipher, R., Vinall, S.L., Xue, L., et al.Pharmacologic profile of OC000459, a potent, selective, and orally active D prostanoid receptor 2 antagonist that inhibits mast cell-dependent activation of T helper 2 lymphocytes and eosinophilsJ. Pharmacol. Exp. Ther.340(2)473-482(2012)
| Cas No. | 851723-84-7 | SDF | |
| 别名 | [5-氟-2-甲基-3-(喹啉-2-基甲基)吲哚-1-基]乙酸,OC000459 | ||
| Canonical SMILES | O=C(O)CN1C(C)=C(CC2=NC3=CC=CC=C3C=C2)C4=C1C=CC(F)=C4 | ||
| 分子式 | C21H17FN2O2 | 分子量 | 348.37 |
| 溶解度 | DMSO: 10 mg/mL (28.71 mM; ultrasonic and warming and heat to 60°C); Water: < 0.1 mg/mL (insoluble) | 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。 |
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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 | 2.8705 mL | 14.3526 mL | 28.7051 mL |
| 5 mM | 0.5741 mL | 2.8705 mL | 5.741 mL |
| 10 mM | 0.2871 mL | 1.4353 mL | 2.8705 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。
Timapiprant, a prostaglandin D2 receptor antagonist, ameliorates pathology in a rat Alzheimer's model
Life Sci Alliance 2022 Sep 27;5(12):e202201555.PMID:36167438DOI:10.26508/lsa.202201555.
We investigated the relevance of the prostaglandin D2 pathway in Alzheimer's disease, because prostaglandin D2 is a major prostaglandin in the brain. Thus, its contribution to Alzheimer's disease merits attention, given the known impact of the prostaglandin E2 pathway in Alzheimer's disease. We used the TgF344-AD transgenic rat model because it exhibits age-dependent and progressive Alzheimer's disease pathology. Prostaglandin D2 levels in hippocampi of TgF344-AD and wild-type littermates were significantly higher than prostaglandin E2. Prostaglandin D2 signals through DP1 and DP2 receptors. Microglial DP1 receptors were more abundant and neuronal DP2 receptors were fewer in TgF344-AD than in wild-type rats. Expression of the major brain prostaglandin D2 synthase (lipocalin-type PGDS) was the highest among 33 genes involved in the prostaglandin D2 and prostaglandin E2 pathways. We treated a subset of rats (wild-type and TgF344-AD males) with Timapiprant, a potent highly selective DP2 antagonist in development for allergic inflammation treatment. Timapiprant significantly mitigated Alzheimer's disease pathology and cognitive deficits in TgF344-AD males. Thus, selective DP2 antagonists have potential as therapeutics to treat Alzheimer's disease.
New Anti-Eosinophil Drugs for Asthma and COPD: Targeting the Trait!
Chest 2017 Dec;152(6):1276-1282.PMID:28583618DOI:10.1016/j.chest.2017.05.019.
Asthma and COPD are prevalent chronic inflammatory airway diseases that are responsible for a large global disease burden. Both diseases are complex and heterogeneous, and they are increasingly recognized as overlapping syndromes that may share similar pathophysiologic mechanisms and treatable traits. Eosinophilic airway inflammation is considered the most influential treatable trait of chronic airway disease, and over the last decade, several monoclonal antibodies and small molecule therapies have been developed to target this trait. These include monoclonal antibodies against IL-5 or IL-5 receptor alpha (mepolizumab, reslizumab, and benralizumab), IL-13 (lebrikizumab and tralokinumab), IL-4 receptor alpha (dupilumab), IgE (omalizumab), and anti-thymic stromal lymphopoietin (tezepelumab) and small molecule therapies such as prostaglandin D2 blockers (fevipiprant and Timapiprant). Although these novel biologic agents have shown promising results in many patients with asthma and COPD who have eosinophilic airway inflammation, it is evident that not all patients respond equally well, despite similar clinical, functional, and inflammatory characteristics. This heterogeneity in treatment response is probably related to different molecular pathways or endotypes leading to eosinophilic airway inflammation, including adaptive immune pathways mediated by T helper 2 cells and innate immune pathways mediated by innate lymphoid cells. The relative contribution of these pathways in asthma and COPD is not yet clarified, and there are currently no reliable biomarkers that represent the various pathways. Therefore, there is an urgent need for easily measurable and reproducible biomarkers that are linked to underlying pathophysiologic disease mechanisms and can predict and monitor responses to novel biologic agents.
Effect of CRTH2 antagonism on the response to experimental rhinovirus infection in asthma: a pilot randomised controlled trial
Thorax 2021 Oct 29;77(10):950-959.PMID:34716281DOI:10.1136/thoraxjnl-2021-217429.
Background and aims: The chemoattractant receptor-homologous molecule expressed on T helper type 2 cells (CRTH2) antagonist Timapiprant improved lung function and asthma control in a phase 2 study, with evidence suggesting reduced exacerbations. We aimed to assess whether Timapiprant attenuated or prevented asthma exacerbations induced by experimental rhinovirus (RV) infection. We furthermore hypothesised that Timapiprant would dampen RV-induced type 2 inflammation and consequently improve antiviral immune responses. Methods: Atopic patients with partially controlled asthma on maintenance inhaled corticosteroids were randomised to Timapiprant (n=22) or placebo (n=22) and challenged with RV-A16 3 weeks later. The primary endpoint was the cumulative lower respiratory symptom score over the 14 days post infection. Upper respiratory symptoms, spirometry, airway hyperresponsiveness, exhaled nitric oxide, RV-A16 virus load and soluble mediators in upper and lower airways samples, and CRTH2 staining in bronchial biopsies were additionally assessed before and during RV-A16 infection. Results: Six subjects discontinued the study and eight were not infected; outcomes were assessed in 16 timapiprant-treated and 14 placebo-treated, successfully infected subjects. There were no differences between treatment groups in clinical exacerbation severity including cumulative lower respiratory symptom score day 0-14 (difference 3.0 (95% CI -29.0 to 17.0), p=0.78), virus load, antiviral immune responses, or RV-A16-induced airway inflammation other than in the bronchial biopsies, where CRTH2 staining was increased during RV-A16 infection in the placebo-treated but not the timapiprant-treated group. Timapiprant had a favourable safety profile, with no deaths, serious adverse events or drug-related withdrawals. Conclusion: Timapiprant treatment had little impact on the clinicopathological changes induced by RV-A16 infection in partially controlled asthma.
Investigation on the use of fused deposition modeling for the production of IR dosage forms containing Timapiprant
Int J Pharm X 2022 Dec 24;5:100152.PMID:36624741DOI:10.1016/j.ijpx.2022.100152.
The present work focused on evaluating the feasibility of fused deposition modeling (FDM) in the development of a dosage form containing Timapiprant (TMP), also known as CHF6532, which is a novel active molecule indicated in the potential treatment of eosinophilic asthma upon oral administration. The resulting product could be an alternative, with potential towards personalization, of immediate release (IR) tablets used in the clinical studies. Formulations based on different polymeric carriers were screened, leading to the identification of a polyvinyl alcohol-based one, which turned out acceptable for versatility in terms of active ingredient content, printability and dissolution performance (i.e. capability to meet the dissolution specification set, envisaging >80% of the drug dissolved within 30 min). Following an in-depth evaluation on the influence of TMP solid state and of the voids volume resulting from printing on dissolution, few prototypes with shapes especially devised for therapy customization were successfully printed and were compliant with the dissolution specification set.