osteoclasts

PFI-4 is a potent and selective and cell-permeable BRPF1 bromodomain inhibitor.

Amakusamine is an indole alkaloid from the sponge of Psammocinia sp. It inhibits RANKL-induced isolation of multinucleated osteoclasts and inhibits RANKL-induced multinucleated osteoclasts.

Sodium etidronate (Didronel) is a synthetic therapeutic diphosphonate analog of endogenous pyrophosphate. As a member of the family of drugs known as bisphosphonates, Sodium etidronate differs from endogenous pyrophosphate in its resistance to enzymatic hydrolysis. This agent adsorbs to hydroxyapatite cells and reduces the number of osteoclasts, thereby inhibiting abnormal bone resorption. Etidronate may also directly stimulate bone formation by osteoblasts.

Strontium ranelate (S12911), a strontium (II) salt of the ranelic acid, is a medication for osteoporosis. Studies indicate it can also slow the course of osteoarthritis of the knee. The drug is unusual in that it both increases deposition of new bone by osteoblasts and reduces the resorption of bone by osteoclasts. It is therefore promoted as a "dual action bone agent" (DABA) indicated for use in the treatment of severe osteoporosis.

Scutellarin (Scutellarein-7-glucuronide), an active flavone isolated from Scutellaria baicalensis, can inhibit RANKL-mediated MAPK and NF-κB signaling pathway in osteoclasts, and down-regulate the STAT3/Girdin/Akt signaling in HCC cells.

Icariside I (Lcariside I) is isolated from Epimedium herb. It can stimulate osteogenic differentiation of BMSCs and inhibit bone resorption activity of osteoclasts.

Cyclosporin B is an immunosuppressant that has revolutionized organ transplantation through its use in the prevention of graft rejection. Cyclosporin B displays antiviral properties, inhibiting the entry of hepatitis B into hepatocytes. Cyclosporin B also

Anti-osteoporosis agent-11 (compound 3k) is an anti-osteoporosis compound targeting osteoclasts. It exhibits its most prominent effect by inhibiting osteoclast differentiation, with an IC50 value of 0.36 μM. Additionally, Anti-osteoporosis agent-11 suppresses osteoclast formation, bone resorption, and the expression of osteoclast-specific genes by blocking the RANKL-induced mitogen-activated protein kinase (MAPK) and NF-κB signaling pathways.

Anti-osteoporosis agent-10 is an inhibitor of osteoporosis that suppresses the formation of osteoclasts with an IC50 of 0.042 μM. It also exhibits antagonistic activity towards PPARγ, with an EC50 value of 0.75 μM.

AubipyOMe serves as an effective inhibitor of Tartrate-resistant Acid Phosphatase (TRAP/ACP5), a metalloenzyme identified in activated osteoclasts and macrophages. It exhibits inhibitory IC50 values of 1.3 μM against TRAP5a and 1.8 μM against TRAP5b. Additionally, it effectively suppresses TRAP activity in extracts from mouse macrophages and human lung tissues.

Methopterin shows the activation and bone resorption function of murine osteoclasts.

JNJ-28312141 is an orally active CSF1R inhibitor and a FLT3 inhibitor. JNJ-28312141 is a new agent with potential therapeutic activity in acute myeloid leukemia and in settings where CSF-1-dependent macrophages and osteoclasts contribute to tumor growth a

Teriparatide acetate (Forteo) is a PHT agonist, with an IC50 of 2 nM in HEK293 cells.Teriparatide acetate is a recombinant form of parathyroid hormone. It is an effective anabolic (i.e., bone growing) agent used to treat some forms of osteoporosis. Intermittent use of Teriparatide acetate activates osteoblasts more than osteoclasts, which leads to an overall increase in bone.

The compound binds and blocks farnesyl diphosphate synthase in the HMG-CoA pathway (IC50 = 460 nM for recombinant human FPPS). It causes macrophage apoptosis and inhibits prenylation and sterol biosynthesis in purified osteoclasts.

AC708 is a small molecule CSF1R inhibitor that effectively inhibits CSF1R phosphorylation mediated by CSF-1 (IC50 = 26 nM) and IL-34 (IC50 = 33 nM). It also inhibited the activity of growth factor-dependent cells cultured in CSF-1 (IC50 = 38 nM) or IL-34

TNF-α antagonist is an exocyclic peptide that mimics the critical TNF-α recognition loop on TNF receptor I complex and, thus, prevents ligand interaction with the receptor. By blocking the TNF receptor ligand contact site, this peptide interferes with both activating receptor activator of NF-κB (RANK) and TNF-α's recruitment and activation of osteoclasts. TNF-α antagonist has been used to block bone resorption in the study of systemic bone loss in rheumatoid arthritis and inflammatory bone destruction.

Reveromycin A is the major component of a complex of spiroketal antibiotics isolated from Streptomyces sp. It inhibits the mitogenic activity of epidermal growth factor in Balb/MK cells (IC50 = 0.7 μg/ml), displays antiproliferative activity against human KB and K562 tumor cell lines (IC50s = 1.9 and 1.6 μg/ml, respectively), and demonstrates antifungal activity against C. albicans (MIC = 2 μg/ml at pH 3). Reveromycin A also has been shown to inhibit bone resorption by inducing apoptosis in osteoclasts with an IC50 value of 0.7 μM.

Calcitonin is a peptide hormone that lowers blood calcium level and inhibits bone resorption. It belongs to the calcitonin family of peptides, which also includes amylin , calcitonin gene-related peptide , and adrenomedullin. The binding of salmon calcitonin to the human calcitonin receptor (CTR) is not modulated by receptor activity-modifying proteins (RAMPs), which influence affinity of human calcitonin to CTR. Salmon calcitonin binds to human CTR2 with IC50 values of 0.933, 0.224, 0.134, and 0.317 nM alone and with RAMP1, 2, or 3, respectively. It induces cAMP accumulation in COS-7 cells transfected with CTR2 (EC50 = 0.166 nM). Salmon calcitonin inhibits bone resorption by osteoclasts in a pit formation assay using rat bone slices (ID50 = 0.003 pg/mL) and lowers calcium level in vivo in a bioassay of hypocalcemia in rats (ED15 = 33.9 mg/kg). Formulations containing salmon calcitonin have been used to treat hypercalcemia, bone destruction by osteoporosis, and Paget's disease.

Relacatib (SB-462795) is a novel, potent, and orally active inhibitor of human cathepsins K, L, and V, exhibiting high affinity with Ki values of 41 pM, 68 pM, and 53 pM, respectively. It effectively inhibits endogenous cathepsin K in situ in human osteoclasts and human osteoclast-mediated bone resorption with IC50 values of 45 nM and 70 nM, respectively. In vitro studies confirm its inhibitory effect on bone resorption in human tissue, and in vivo studies on cynomolgus monkeys validate its efficacy in reducing bone resorption.

Alisol B may be a potential novel therapeutic molecule for bone disorders through targeting the differentiation of osteoclasts as well as their functions. Alisol B also inhibited RANKL-induced expression of NFATc1 and c-Fos, which are key transcription factors for osteoclastogenesis.

Cantharidin imide is a PP1/2A inhibitor found in Canarthis vesicatoria. It inhibits proliferation of colorectal cancer cells, increases MCP-1, IL-6, and IL-β levels, and inhibits differentiation and resorptive activity of osteoclasts. This compound can produce severe skin inflammation, and is extremely toxic if ingested orally.

Anti-osteoporosis agent-4 (Compound 11h) suppresses the differentiation of primary osteoclasts and attenuates RANKL-induced osteoclastogenesis, effectively inhibiting osteoclast formation with an IC50 value of 358.29 nM, and impedes the activation of the PI3K/AKT and IκBα/NF-κB signaling pathways [1].

1,3-Dibenzyl-5-fluorouracil is a chemical inhibitor that suppresses the formation of osteoclasts, functioning by downregulating the signaling pathways of nuclear factor κB ligand receptor activator (Receptor activator of NF-κB ligand, RANKL) and macrophage colony-stimulating factor (M-CSF). This compound is used in the research of metabolic bone diseases.

WAY-325371 can inhibit the formation of osteoclasts.