| Target Validation Information | |||||
|---|---|---|---|---|---|
| Target ID | T23172 | ||||
| Target Name | Tyrosine-protein kinase JAK3 | ||||
| Target Type | Successful |
||||
| Drug Potency against Target | 6-o-tolylquinazolin-2-amine | Drug Info | IC50 = 9819 nM | [528429] | |
| Tofacitinib | Drug Info | IC50 = 1 nM | [552773] | ||
| Atropisomer 1 | Drug Info | IC50 = 1530 nM | [530583] | ||
| Action against Disease Model | Tofacitinib | A specific orally active inhibitor of JAK3, CP-690,550, significantly prolonged survival in a murine model of heart transplantation and in cynomolgus monkeys receiving kidney transplants. CP-690,550 treatment was not associated with hypertension, hyperlipidemia, or lymphoproliferative disease. On the basis of these preclinical results, we believe JAK3 blockade by CP-690,550 has potential for therapeutically desirable immunosuppression in h uMan organ transplantation and in other clinical setting | [552391] | Drug Info | |
| The Effect of Target Knockout, Knockdown or Genetic Variations | JAK3 knockout mice and JAK3 deficient patients cannot signal through the interleukin-2,4,7,9,or 15 receptors and suffer from severe combined immunodeficiency (SCID).JAKl and JAK2 knockout mice do not survive,their cells again showing distinct patterns of cytokine signaling deficits.Dificent IL-2,IL-4,IL-7 in JAK3-/- knockout mice | [552391] | |||
| References | |||||
| Ref 552391 | Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor. Science. 2003 Oct 31;302(5646):875-8. | ||||
| Ref 528429 | J Med Chem. 2006 Sep 21;49(19):5671-86.Discovery of aminoquinazolines as potent, orally bioavailable inhibitors of Lck: synthesis, SAR, and in vivo anti-inflammatory activity. | ||||
| Ref 552773 | A quantitative analysis of kinase inhibitor selectivity. Nat Biotechnol. 2008 Jan;26(1):127-32. doi: 10.1038/nbt1358. | ||||
| Ref 530583 | J Med Chem. 2009 Dec 24;52(24):7938-41.Janus kinase 2 inhibitors. Synthesis and characterization of a novel polycyclic azaindole. | ||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.