RANKL
Synonyms
Osteoclast differentiation factor, TRANCE, TNFSF11, TNF-related activation-induced cytokine, Tumor necrosis factor ligand superfamily member 11, CD254, TNF Superfamily Member 11, Osteoprotegerin Ligand, Receptor Activator Of Nuclear Factor Kappa B Ligand, Tumor Necrosis Factor Superfamily Member 11, CD254 Antigen, HRANKL2, TNLG6B, OPTB2, SOdf, RANK Ligand, ODF, RANKL, OPGL, Tumor Necrosis Factor (Ligand) Superfamily, Member 11, Receptor Activator Of Nuclear Factor Kappa-B Ligand, Tumor Necrosis Factor Ligand 6B
Description
Receptor activator of nuclear factor kappa-Β ligand (RANKL), also known as tumor necrosis factor ligand superfamily member 11 (TNFSF11), TNF-related activation-induced cytokine (TRANCE), osteoprotegerin ligand (OPGL), and osteoclast differentiation factor (ODF), is a protein that in humans is encoded by the TNFSF11 gene. It is a 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 . Induces osteoclastogenesis by activating multiple signaling pathways in osteoclast precursor cells, chief among which is induction of long lasting oscillations in the intracellular concentration of Ca (2+) resulting in the activation of NFATC1, which translocates to the nucleus and induces osteoclast-specific gene transcription to allow differentiation of osteoclasts. During osteoclast differentiation, in a TMEM64 and ATP2A2-dependent manner induces activation of CREB1 and mitochondrial ROS generation necessary for proper osteoclast generation.
KO Status
F0
Drug Information
Launched drug: 1
Drugs in clinical trials: 18
Latest Research Phase: Approved
Drug Name
Code
Phase
Company
Indications
Clinical Trials
Denosumab
AMG-162, NSC-744010
Approved
Amgen Inc
Bone metastases, Solid tumours, Cataract, Kidney Neoplasms, Hematologic Neoplasms, Head and Neck Neoplasms, Endocrine Gland Neoplasms, Osteoporosis, Bone Diseases, Metabolic, Parathyroid Neoplasms, Carcinoma, Osteoporosis, Postmenopausal, Colonic Neoplasms, Hodgkin Disease, Arthritis, Rheumatoid, Kidney Diseases, Hypercalcemia, Prostatic Neoplasms, Castration-Resistant, Multiple Myeloma, Osteogenesis Imperfecta, Prostatic Neoplasms, Breast Neoplasms, Giant Cell Tumors, Giant Cell Tumor of Bone, Bone Neoplasms, Fractures, Bone, Thyroid Neoplasms, Lung Neoplasms, Lymphoma, Non-Hodgkin, Lymphoma, Neoplasm Metastasis, Carcinoma, Non-Small-Cell Lung
Recombinant human anti-RANKL antibody (Jiangsu T-mab BioPharma)
MW031, MW032, TK-006
Phase 3 Clinical
Jiangsu T-Mab Biopharma
Bone metastases, Solid tumours, Osteoporosis, Osteoporosis, Postmenopausal, Breast Neoplasms, Bone Neoplasms
Denosumab biosimilar (Intas Biopharmaceuticals)
Phase 3 Clinical
Intas Biopharmaceuticals
Osteoporosis, Postmenopausal
Denosumab biosimilar (Boan Biopharma/Luye Pharma)
LY-06006, LY-01011
Phase 3 Clinical
Shandong Boan Biotechnology Co Ltd, Luye Pharma Group Ltd
Bone metastases, Osteoporosis, Osteoporosis, Postmenopausal, Bone Neoplasms, Neoplasm Metastasis
Denosumab biosimilar (Sandoz)
GP-2411
Phase 3 Clinical
Novartis Pharma Ag, Sandoz
Osteoporosis, Postmenopausal
Recombinant human anti-RANKL momoclonal antibody (Qilu Pharmaceutical)
Phase 3 Clinical
Qilu Pharmaceutical Co Ltd
Osteoporosis, Postmenopausal, Neoplasms
Recombinant human anti-RANKL antibody (Alphamab)
KN-012
Phase 3 Clinical
Suzhou Alphamab Co Ltd
Osteoporosis, Postmenopausal
Denosumab biosimiliar (Celltrion)
CT-P41
Phase 3 Clinical
Celltrion
Osteoporosis, Postmenopausal
Denosumab biosimilar (Samsung Bioepis)
SB-16
Phase 3 Clinical
Samsung Bioepis
Osteoporosis, Postmenopausal
Denosumab biosimilar (Qilu Pharma)
QL-1206
Phase 3 Clinical
Qilu Pharmaceutical Co Ltd
Bone metastases, Osteoporosis, Postmenopausal
References
Title
Authors
Source
A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function
Anderson D.M., Maraskovsky E., Billingsley W.L., Dougall W.C., Tometsko M.E., Roux E.R., Teepe M.C., DuBose R.F., Cosman D., Galibert L.,
Nature 390:175-179(1997)
Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation
Lacey D.L., Timms E., Tan H.-L., Kelley M.J., Dunstan C.R., Burgess T., Elliott R., Colombero A., Elliott G., Scully S., Hsu H., Sullivan J., Hawkins N., Davy E., Capparelli C., Eli A., Qian Y.-X., Kaufman S., Boyle W.J.,
Cell 93:165-176(1998)
Cancer cells responsible for humoral hypercalcemia express mRNA encoding a secreted form of ODF/TRANCE that induces osteoclast formation
Nagai M., Kyakumoto S., Sato N.,
Biochem. Biophys. Res. Commun. 269:532-536(2000)
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)
The MGC Project Team,
Genome Res. 14:2121-2127(2004)
TRANCE is a novel ligand of the tumor necrosis factor receptor family that activates c-Jun N-terminal kinase in T cells
Wong B.R., Rho J., Arron J., Robinson E., Orlinick J., Chao M., Kalachikov S., Cayani E., Bartlett F.S. III, Frankel W.N., Lee S.Y., Choi Y.,
J. Biol. Chem. 272:25190-25194(1997)
Crystal structure of human RANKL complexed with its decoy receptor osteoprotegerin
Luan X., Lu Q., Jiang Y., Zhang S., Wang Q., Yuan H., Zhao W., Wang J., Wang X.,
J. Immunol. 189:245-252(2012)
Osteoclast-poor human osteopetrosis due to mutations in the gene encoding RANKL
Sobacchi C., Frattini A., Guerrini M.M., Abinun M., Pangrazio A., Susani L., Bredius R., Mancini G., Cant A., Bishop N., Grabowski P., Del Fattore A., Messina C., Errigo G., Coxon F.P., Scott D.I., Teti A., Rogers M.J., Helfrich M.H.,
Nat. Genet. 39:960-962(2007)