AZD1981

製品コードS7263 バッチS726301

化学情報

	Synonyms	N/A	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₁₉H₁₇ClN₂O₃S
	分子量	388.87	CAS No.	802904-66-1
Solubility (25°C)*	体外	DMSO	11 mg/mL (28.28 mM)
		Water	Insoluble
		Ethanol	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	AZD1981 is a potent, selective CRTh2 (DP2) receptor antagonist with IC50 of 4 nM, showing >1000-fold selectivity over more than 340 other enzymes and receptors, including DP1. Phase 2.
in vitro	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. ^[1] 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. ^[2]
in vivo	AZD1981 has high oral bioavailability in male sprague dawley rats. ^[1] In guinea pig hind limb model, AZD1981 (100 nM) completely inhibits DK-PGD2-induced eosinophil mobilization. ^[2]
特徴	An orally available selective DP2(CRTh2) receptor antagonist in clinical development for asthma.

プロトコル(参考用のみ)

キナーゼアッセイ	DP2 binding studies
キナーゼアッセイ	A scintillation proximity assay (SPA) following [³H]PGD2 binding to membranes of HEK cells expressing recombinant DP2 is used. The potency of AZD1981 as an antagonist is determined by quantifying its ability to displace specific radio-ligand binding. Briefly, membranes from HEK293 expressing recombinant human DP2 are pre-bound to Wheat Germ Agglutinin-coated PVT-SPA beads for 18 h at 4°C. Assays were started by the addition of 25 μL of membrane-coated beads (10 mg/mL of beads) to an assay buffer (50 mm HEPES pH 7.4 containing 5 mm MgCl₂) containing 2.5 nM [³H]PGD2 in the absence or the presence of increasing concentrations of the tested compounds (50 μL final volume). Non-specific binding is determined in the same conditions but in the presence of 10 μM DK-PGD2. Plates are incubated for 2 h at room temperature, and bead-associated radioactivity is measured using a Wallac Microbeta counter. The concentration of the compounds causing 50% inhibition of binding of [³H]PGD2 to the receptor is calculated (IC50). Ki values have not been derived from IC50, as there is no evidence of a simple competitive interaction with PGD2. The same methodology is used for recombinant human, murine, rat, guinea pig, dog and rabbit DP2. Reversibility of binding to the human receptor was assessed by recovery of [³H]PGD2 binding after removal of AZD1981 by washing of the membrane-coated SPA beads. HEK-membrane-coated beads are incubated in the presence of AZD1981 for 2 h at room temperature to bind the compound to DP2. To remove the bound AZD1981, beads are centrifuged (1 min at 1300× g), and the pellet resuspended in 1 mL of assay buffer. This is repeated four times. Aliquots (30 μL) are transferred to 96-well plates, and [³H]PGD2 binding is evaluated as above. Parallel samples containing (i) 10 μM DK-PGD2 during the 2 h incubation and in the wash buffer; (ii) AZD1981 at 2 μM in the wash buffer; and (iii) vehicle are processed alongside to determine non-specific binding and the ‘no wash’ condition whilst controlling for loss of beads during the washing process. The time from first wash to end of first reading is approximately 13 min.
動物実験	動物モデル	Male sprague dawley rats.
	投薬量	1 mg/kg(i.v.), 4 mg/kg(oral)
	投与方法	i.v. or oral administration

参考

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Target Deconvolution of a Multikinase Inhibitor with Antimetastatic Properties Identifies TAOK3 as a Key Contributor to a Cancer Stem Cell-Like Phenotype. [ Mol Cancer Ther, 2019, 18(11):2097-2110]	PubMed: 31395684

Target Deconvolution of a Multikinase Inhibitor with Antimetastatic Properties Identifies TAOK3 as a Key Contributor to a Cancer Stem Cell-Like Phenotype. [ Mol Cancer Ther, 2019, 18(11):2097-2110]

PubMed: 31395684

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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