Osteoclast-targeting small molecules for the treatment of neoplastic bone metastases.
Osteoclasts are highly specialized cells that resorb bone, and their abnormal activity is implicated in a variety of human bone diseases. In neoplastic bone metastasis, the bone destruction caused by osteoclasts is not only associated with the formation and progression of metastatic lesions, but also could contribute to frequent complications such as severe pain and pathological fractures, which greatly diminish the quality of life of patients. Bisphosphonates, potent antiresorptive drugs, have been shown to have efficacy for treating bone metastases in many types of cancer, and the development of various molecularly targeted agents is currently proceeding. Thus, inhibition of osteoclast function is now established as an important treatment strategy for bony metastases. This review focuses on promising small molecules that disrupt osteoclast function and introduces our chemical/biological approach for identifying osteoclast-targeting small molecular inhibitors.
Kawatani
Makoto
M
Antibiotics Laboratory, Chemical Biology Department, Advanced Science Institute, RIKEN, Wako-shi, Saitama, Japan.
Osada
Hiroyuki
H
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D001862:Bone Resorption / Q000209:etiology; D000081247:CSK Tyrosine-Protein Kinase; D002454:Cell Differentiation; D004164:Diphosphonates / Q000494:pharmacology; D004987:Ethers / Q000494:pharmacology; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors; D010010:Osteoclasts / Q000187:drug effects* / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011714:Pyrans / Q000494:pharmacology; D013141:Spiro Compounds / Q000494:pharmacology; D019061:src-Family Kinases
C477902:4-carboxy-5,5'-dihydroxy-3,3'-dimethyl-diphenylether; D000970:Antineoplastic Agents; D001713:Biphenyl Compounds; D004164:Diphosphonates; D004987:Ethers; D039302:Integrin alphaVbeta3; D011714:Pyrans; D013141:Spiro Compounds; C068098:reveromycin A; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human