| Target Validation Information | |||||
|---|---|---|---|---|---|
| Target ID | T63414 | ||||
| Target Name | P2X purinoceptor 7 | ||||
| Target Type | Clinical Trial |
||||
| Drug Potency against Target | STYLISSADINE A | Drug Info | IC50 = 700 nM | [530221] | |
| STYLISSADINE B | Drug Info | IC50 = 1800 nM | [530221] | ||
| A-740003 | Drug Info | IC50 = 18 nM | [530221] | ||
| [3H]A-804598 | Drug Info | IC50 = 10 nM | [530221] | ||
| KN-62 | Drug Info | IC50 = 110 nM | [530421] | ||
| Action against Disease Model | AZD9056 | The P2X7 receptor antagonist AZD9056 has been evaluated in preclinical models of RA with promising results (the results were classified as unpublished in this report) | Drug Info | ||
| The Effect of Target Knockout, Knockdown or Genetic Variations | We monitored gland secretions in in vivo preparations of wild-type and P2X(7)(-/-) (Pfizer) mice stimulated with pilocarpine. In cell preparations from pancreas, parotid and lacrimal glands we measured ATP release and intracellular Ca(2+) activity using Fura-2. The data showed that pancreatic secretion and salivary secretions were reduced in P2X(7)(-/-) mice, and in contrast, tear secretion was increased in P2X(7)(-/-) mice. The secretory phenotype was also dependent on the sex of the animal, such that males were more dependent on the P2X(7) receptor expression. ATP release in all cell preparations could be elicited by carbachol and other agonists, and this was independent of the P2X(7) receptor expression. ATP and carbachol increased intracellular Ca(2+) activity, but responses depended on the gland type, presence of the P2X(7) receptor and the sex of the animal. Together, these results demonstrate that cholinergic stimulation leads to release of ATP that can via P2X(7) receptors up-regulate pancreatic and salivary secretion but down-regulate tear secretion | [530221] | |||
| References | |||||
| Ref 530221 | Bioorg Med Chem. 2009 Jul 15;17(14):4861-5. Epub 2009 Jun 12.Purinergic P2X(7) receptor antagonists: Chemistry and fundamentals of biological screening. | ||||
| Ref 530221 | Bioorg Med Chem. 2009 Jul 15;17(14):4861-5. Epub 2009 Jun 12.Purinergic P2X(7) receptor antagonists: Chemistry and fundamentals of biological screening. | ||||
| Ref 530221 | Bioorg Med Chem. 2009 Jul 15;17(14):4861-5. Epub 2009 Jun 12.Purinergic P2X(7) receptor antagonists: Chemistry and fundamentals of biological screening. | ||||
| Ref 530221 | Bioorg Med Chem. 2009 Jul 15;17(14):4861-5. Epub 2009 Jun 12.Purinergic P2X(7) receptor antagonists: Chemistry and fundamentals of biological screening. | ||||
| Ref 530421 | Bioorg Med Chem Lett. 2009 Nov 1;19(21):6053-8. Epub 2009 Sep 17.Synthesis and structure-activity relationships of pyrazolodiazepine derivatives as human P2X7 receptor antagonists. | ||||
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