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)