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.
理化性质和储存条件
| Molecular Weight (MW) | 388.87 |
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| Formula | C19H17ClN2O3S |
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| CAS No. | 802904-66-1 |
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| Storage | -20℃ for 3 years in powder form |
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| -80℃ for 2 years in solvent |
| Solubility (In vitro) | DMSO: 11 mg/mL (28.3 mM) |
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| Water: <1 mg/mL |
| Ethanol:<1 mg/mL |
| SMILES | O=C(O)CN1C(C)=C(SC2=CC=C(Cl)C=C2)C3=C1C=CC=C3NC(C)=O |
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| Synonyms | AZD1981; AZD-1981; AZD 1981 |
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实验参考方法
| In 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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| In 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 model | Guinea pig hind limb model |
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| Formulation & Dosage | 10 nM |
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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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