Target Information

Target General Infomation
Target ID
T21334
Former ID
TTDC00224
Target Name
Tumor necrosis factor ligand superfamily member 11
Gene Name
TNFSF11
Synonyms
ODF; OPGL; Osteoclast differentiation factor; Osteoprotegerin ligand; RANKL; Receptor activatorof nuclear factor kappa B ligand; TNF-related activation-induced cytokine; TRANCE; TNFSF11
Target Type
Successful
Disease Bone metastases [ICD9: 198.5; ICD10: C79.51]
Bone metastases in prostate cancer [ICD9: 185, 198.5; ICD10: C61, C79.51]
Osteoporosis [ICD9: 733.0, V07.4; ICD10: M80-M81, Z79.890]
Postmenopausal osteoporosis [ICD9: 733; ICD10: M80-M81]
Rheumatoid arthritis [ICD9: 710-719, 714; ICD10: M05-M06]
Function
Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A/RANK. Osteoclast differentiation and activation factor. Augments the ability of dendritic cells to stimulate naive T-cell proliferation. May be an important regulator of interactions between T-cells and dendritic cells and may play a role in the regulation of the T-cell-dependent immune response. May also play an important role in enhanced bone-resorption in humoral hypercalcemia of malignancy.
BioChemical Class
Cytokine: tumor necrosis factor
Target Validation
T21334
UniProt ID
O14788
Sequence
MRRASRDYTKYLRGSEEMGGGPGAPHEGPLHAPPPPAPHQPPAASRSMFVALLGLGLGQV
VCSVALFFYFRAQMDPNRISEDGTHCIYRILRLHENADFQDTTLESQDTKLIPDSCRRIK
QAFQGAVQKELQHIVGSQHIRAEKAMVDGSWLDLAKRSKLEAQPFAHLTINATDIPSGSH
KVSLSSWYHDRGWAKISNMTFSNGKLIVNQDGFYYLYANICFRHHETSGDLATEYLQLMV
YVTKTSIKIPSSHTLMKGGSTKYWSGNSEFHFYSINVGGFFKLRSGEEISIEVSNPSLLD
PDQDATYFGAFKVRDID
Drugs and Mode of Action
Drug(s) Denosumab Drug Info Approved Postmenopausal osteoporosis [531351], [541943]
Denosumab Drug Info Phase 3 Bone metastases in prostate cancer [531351], [541943]
Denosumab Drug Info Phase 2 Rheumatoid arthritis [531351], [541943]
ALX-0141 Drug Info Phase 1 Osteoporosis [549005]
CEP-37251 Drug Info Phase 1 Bone metastases [523109]
Inhibitor ALX-0141 Drug Info [550190]
CEP-37251 Drug Info [551200]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Cytokine-cytokine receptor interaction
NF-kappa B signaling pathway
Osteoclast differentiation
Prolactin signaling pathway
Rheumatoid arthritis
NetPath Pathway Leptin Signaling Pathway
TWEAK Signaling Pathway
Pathway Interaction Database IL6-mediated signaling events
Reactome TNFR2 non-canonical NF-kB pathway
TNFs bind their physiological receptors
TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway
WikiPathways Osteoblast Signaling
Vitamin D Receptor Pathway
Differentiation Pathway
RANKL/RANK Signaling Pathway
Osteoclast Signaling
References
Ref 523109ClinicalTrials.gov (NCT01159873) Single Ascending-Dose Study to Characterize the Safety, Pharmacokinetics, and Pharmacodynamics of CEP-37251 in Healthy Postmenopausal Women. U.S. National Institutes of Health.
Ref 531351Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
Ref 541943(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6886).
Ref 549005Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031383)
Ref 531351Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
Ref 550190Clinical pipeline report, company report or official report of Ablynx.
Ref 551200This week in therapeutics Cancer. SciBX 3(40); doi:10.1038/scibx.2010.1202. Oct. 14, 2010

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