| Target Validation Information | |||||
|---|---|---|---|---|---|
| Target ID | T21334 | ||||
| Target Name | Tumor necrosis factor ligand superfamily member 11 | ||||
| Target Type | Successful |
||||
| Drug Potency against Target | Denosumab | Drug Info | IC50 < 1 nM | [552887] | |
| Action against Disease Model | Denosumab | Denos uMab and h uMan OPG-Fc inhibited the ability of h uMan RANKL (143-317) to stimulate the formation of osteoclasts derived from murine RAW 264.7 cells, with IC50 values of 1.64 and 1.15 nM, respectively. | [552582] | Drug Info | |
| The Effect of Target Knockout, Knockdown or Genetic Variations | NF-kappaB is a pleiotropic transcription factor, which regulates osteoclast formation, function, and survival. The finding that the deletion of both NF-kappaB p50 and p52 subunits resulted in osteopetrosis due to the absence of osteoclasts was followed by the observation that NF-kappaB is essential for RANK-expressing osteoclast precursors to differentiate into TRAP+ osteoclasts in response to RANKL and other osteoclastogenic cytokines. Thus, inhibitors of NF-kappaB should prevent osteoclast formation induced directly or indirectly by RANKL or TNF. | [552887] | |||
| References | |||||
| Ref 552887 | Denosumab, a fully human monoclonal antibody to RANKL, inhibits bone resorption and increases BMD in knock-in mice that express chimeric (murine/human) RANKL. J Bone Miner Res. 2009 Feb;24(2):182-95. doi: 10.1359/jbmr.081112. | ||||
| Ref 552582 | CCK1 receptor antagonist, dexloxiglumide: effects on human isolated gallbladder. Potential clinical applications. Minerva Gastroenterol Dietol. 2003 Sep;49(3):211-6. | ||||
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