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AZD1981 is a novel potent and selective CRTh2 (Chemoattractant receptor-homologous molecule expressed on TH2 cells; DP2-Prostaglandin D2 receptor 2, ) receptor antagonist with IC50 of 4 nM, it displayed >1000-fold selectivity over more than 340 other enzymes and receptors, including DP1. AZD1981 has shown to inhibit eosinophil migration with a pIC50 value of 7.6±0.1. It could block chemotaxis of DP2+ T-cell lines with a pIC50 value of 7.5±0.1. AZD1981 inhibited PGD2 by binding to mouse, rat, rabbit, dog, guinea pig and human DP2. AZD1981 is currently being developed for the treatment of asthma.
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Physicochemical Properties
| Molecular Formula |
C19H17CLN2O3S
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| Molecular Weight |
388.87
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| Exact Mass |
388.065
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| CAS # |
802904-66-1
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| Related CAS # |
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| PubChem CID |
11292191
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| Appearance |
White to gray solid powder
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| LogP |
5.446
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
26
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| Complexity |
527
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
JWYIGNODXSRKGP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H17ClN2O3S/c1-11-19(26-14-8-6-13(20)7-9-14)18-15(21-12(2)23)4-3-5-16(18)22(11)10-17(24)25/h3-9H,10H2,1-2H3,(H,21,23)(H,24,25)
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| Chemical Name |
2-[4-acetamido-3-(4-chlorophenyl)sulfanyl-2-methylindol-1-yl]acetic acid
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| Synonyms |
| AZD1981; AZD-1981; AZD 1981 |
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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
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| 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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Biological Activity
| ln Vitro |
In vitro activity: AZD1981, as a potent antagonist in a disease relevant cell system, inhibits DK-PGD2-induced CD11b expression in human eosinophils with IC50 of 10 nM. AZD1981 blocks DP2-mediated shape change in human eosinophils and basophils in blood, as well as DP2-mediated chemotaxis of human Th2 cells and eosinophils. Moreover, AZD1981 also blocks the binding of [3H]PGD2 to mouse, rat, guinea pig, rabbit and dog recombinant DP2.
Kinase Assay: AZD1981 is a novel potent and selective CRTh2 (DP2) receptor antagonist with IC50 of 4 nM, it displayed >1000-fold selectivity over more than 340 other enzymes and receptors, including DP1.
Cell Assay: AZD1981 could block chemotaxis of DP2+ T-cell lines with a pIC50 value of 7.5±0.1. AZD1981 has been demonstrated to inhibit PGD2 binding to mouse, rat, rabbit, dog, guinea pig and human DP2. AZD1981 could inhibit shape change induced by DP2 in dog and guinea pig granulocytes as well as in human eosinophils and basophils in blood. |
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| ln Vivo |
| Using the previously described guinea pig hind limb model , 10 nM AZD1981 significantly inhibited DK-PGD2-induced eosinophil mobilization by approximately 50%, and the response was completely inhibited with 100 nM AZD1981. AZD1981 exhibited good cross-species binding activity against mouse, rat, guinea pig, rabbit and dog DP2 . Evaluation in mouse, rat or rabbit cell systems was not possible as they did not respond to DP2 agonists. Agonist responses were seen in guinea pig and dog, and AZD1981 blocked DP2 -mediated eosinophil shape change. Such responses were more robust in the guinea pig, where AZD1981 also blocked DP2 -dependent eosinophil emigration from bone marrow. AZD1981 has high oral bioavailability in male sprague dawley rats. In guinea pig hind limb model, AZD1981 (100 nM) completely inhibits DK-PGD2-induced eosinophil mobilization. |
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| Animal Protocol |
| 10 nM | | Guinea pig hind limb model | |
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| References |
Br J Pharmacol.2013 Apr;168(7):1626-38;Bioorg Med Chem Lett.2011 Nov 1;21(21):6288-92.
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| Additional Infomation |
AZD1981 has been used in trials studying the treatment and basic science of Asthma, Postmenopausal, Pharmakokinetic, Asthma Patients, and Drug Interaction, among others.
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Solubility Data
| Solubility (In Vitro) |
| DMSO: 11 mg/mL (28.3 mM) | | Water:<1 mg/mL | | Ethanol:<1 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.43 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.)
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| Preparing Stock Solutions |
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1 mg |
5 mg |
10 mg |
| 1 mM |
2.5716 mL |
12.8578 mL |
25.7155 mL |
| 5 mM |
0.5143 mL |
2.5716 mL |
5.1431 mL |
| 10 mM |
0.2572 mL |
1.2858 mL |
2.5716 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. |
