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| 1mg |
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| 5mg |
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| 10mg |
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| 50mg |
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| Targets |
Vidupiprant targets two prostaglandin D2 receptors: CRTH2 (DP2) and DP (DP1). Prostaglandin D2 is a lipid mediator involved in allergic and inflammatory responses, particularly in asthma and other Th2-driven conditions. CRTH2 is expressed on Th2 cells, eosinophils, and basophils, and its activation promotes chemotaxis and activation of these cells. By acting as a dual antagonist at both CRTH2 and DP, vidupiprant blocks the pro-inflammatory effects of prostaglandin D2. The compound exhibits IC50 values of 8 nM for CRTH2 and 35 nM for DP, demonstrating high potency at both targets.
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| ln Vitro |
Vidupiprant (AMG 853, Compound 2) has a Kb of 0.2 nM and inhibits the downregulation of CRTH2 on CD16-negative granulocytes (eosinophils) in human whole blood caused by prostaglandin D2 (PGD2). Additionally, at a Kb of 4.7 nM, vidupiprant significantly reduced the PGD2-induced cAMP responses in human whole blood platelets by 80%, in contrast to AMG 009's Kb of 148 nM. Additionally, Vidupiprant was compared to the CRTH2 receptor downregulation human whole blood assay in the aequorin assay utilizing CRTH2-transfected HEK 293 cells and the eosinophil shape change assay [1].
In vitro, vidupiprant acts as a potent antagonist at both CRTH2 and DP receptors. It inhibits CRTH2-mediated signaling with an IC50 of 8 nM and DP-mediated signaling with an IC50 of 35 nM. The compound suppresses eosinophil activation and migration, as well as Th2-driven inflammatory responses. These in vitro studies confirm the dual antagonistic activity of vidupiprant and support its potential as a therapeutic agent for asthma and other allergic diseases. |
| ln Vivo |
In a guinea pig model of PGD2-induced airway constriction, Vidupiprant (AMG 853, Compound 2) showed much higher DP potency in vivo compared to AMG 009. Based on the PGD2 challenge, airway resistance is calculated in this model. The guinea pig whole blood cAMP assay was used to evaluate the in vitro DP potency. AMG 009 has a Kb of 82 nM, compared to 5 nM for Vidupiprant[1].
In vivo, vidupiprant has been investigated in clinical trials for the treatment of asthma. As an orally active dual antagonist of CRTH2 and DP, it has the potential to reduce airway inflammation and improve asthma control. By blocking DP2 signaling, vidupiprant suppresses eosinophil activation and migration, which are key drivers of airway inflammation in asthma. Clinical trials have evaluated its efficacy in reducing asthma exacerbations and improving lung function. |
| Enzyme Assay |
The in vitro enzyme/receptor binding (non-cellular) assays for vidupiprant are radioligand binding assays using membrane preparations from cells expressing recombinant human CRTH2 or DP receptors. The compound's binding affinity (IC50) is determined by its ability to displace a labeled ligand from the receptor. Functional assays may also be performed to measure the compound's ability to inhibit receptor-mediated signaling. These assays confirm the direct interaction of vidupiprant with both CRTH2 and DP receptors and provide quantitative measures of its potency.
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| Cell Assay |
In vitro cellular assays for vidupiprant are performed using cell lines expressing CRTH2 or DP receptors, or using primary cells such as eosinophils or Th2 cells. The compound's antagonist activity is assessed by measuring its ability to inhibit prostaglandin D2-induced chemotaxis, calcium mobilization, or other downstream signaling events. Eosinophil activation and migration are also evaluated in response to prostaglandin D2 in the presence of vidupiprant. These assays confirm the functional antagonism of vidupiprant at both receptors.
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| Animal Protocol |
In vivo animal experiments for vidupiprant have been conducted in models of allergic airway inflammation. Mice or rats are sensitized and challenged with an allergen (e.g., ovalbumin) to induce airway inflammation, and vidupiprant is administered orally. Endpoints include airway hyperresponsiveness, eosinophil infiltration into the lung, and levels of inflammatory cytokines in bronchoalveolar lavage fluid. Clinical trials have also been conducted in humans to evaluate the compound's efficacy in asthma.
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| ADME/Pharmacokinetics |
Vidupiprant has a molecular weight of 609.49 g/mol and a molecular formula of C28H27Cl2FN2O6S. The compound is orally active. Detailed pharmacokinetic parameters such as half-life, Cmax, and bioavailability are not extensively reported in the available literature, but the compound's clinical development suggests adequate pharmacokinetic properties for therapeutic use. Vidupiprant has been evaluated in human trials for asthma, indicating that it has suitable pharmacokinetic and safety profiles for clinical investigation.
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| Toxicity/Toxicokinetics |
Vidupiprant has been evaluated in clinical trials and has been reported to be well-tolerated. Common adverse effects may include mild to moderate gastrointestinal disturbances, headache, or other treatment-emergent adverse events. No significant safety concerns have been reported in clinical trials. However, as with any investigational drug, comprehensive safety data would be required for regulatory approval. The compound's dual antagonism of CRTH2 and DP may offer a favorable safety profile with targeted anti-inflammatory effects.
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| References | |
| Additional Infomation |
Vidupiprant has been used in trials investigating asthma treatment and basic science.
Vidupiprant is a potent and orally active dual antagonist of CRTH2 and DP, with IC50 values of 8 nM and 35 nM, respectively. It has been investigated for the treatment of allergic and inflammatory conditions, particularly asthma and eosinophilic disorders. The compound suppresses eosinophil activation, migration, and Th2-driven inflammatory responses by blocking DP2 signaling. Vidupiprant has been evaluated in clinical trials for asthma but is not an approved drug. It represents a potential therapeutic approach for Th2-mediated inflammatory diseases. |
| Molecular Formula |
C28H27CL2FN2O6S
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| Molecular Weight |
609.4904
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| Exact Mass |
608.095
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| CAS # |
1169483-24-2
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| PubChem CID |
42641863
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| Appearance |
White to off-white solid powder
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| LogP |
8.303
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
40
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| Complexity |
1020
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
PFWVGKROPKKEDW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C28H27Cl2FN2O6S/c1-28(2,3)32-27(36)17-6-8-23(39-24-14-21(31)18(11-19(24)29)13-26(34)35)22(12-17)33-40(37,38)25-9-7-16(10-20(25)30)15-4-5-15/h6-12,14-15,33H,4-5,13H2,1-3H3,(H,32,36)(H,34,35)
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| Chemical Name |
2-[4-[4-(tert-butylcarbamoyl)-2-[(2-chloro-4-cyclopropylphenyl)sulfonylamino]phenoxy]-5-chloro-2-fluorophenyl]acetic acid
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| Synonyms |
AMG-853; AMG 853; AMG853
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~164.07 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.10 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6407 mL | 8.2036 mL | 16.4072 mL | |
| 5 mM | 0.3281 mL | 1.6407 mL | 3.2814 mL | |
| 10 mM | 0.1641 mL | 0.8204 mL | 1.6407 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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