bone loss

Droloxifene (3-Hydroxytamoxifen), a tamoxifen derivative, is an oral active and selective estrogen receptor modulator.Droloxifene induced p53 expression and apoptosis in McF-7 cells.Fluroxifene has anti-estrogen and anti-implantation effects.Fluroxifene prevented bone loss in ovariectomized rats.

Cimicifugoside H1 shows the protective function to cerebral neuron during cerebral ischemia.

Sciadopitysin may prevent the development of diabetic osteopathy, it exerts its therapeutic effects via upregulation of mitochondrial biogenesis.Sciadopitysin shows protective effects on antimycin A-induced toxicity in osteoblastic MC3T3-E1 cells, it may

L-006235 is a potent and reversible inhibitor of cathepsin K with IC50 of 0.25 nM.

1. Curculigoside (Curculigoside A) can prevent bone loss , improve osteogenesis and inhibit osteoclastogenesis of hAFSCs, suggesting its potential use to regulate hAFSC osteogenic differentiation for treating bone disorders. 2. Curculigoside can promote calcium deposition and increase the levels of ALP and Runx2 in osteoblasts under oxidative stress via anti-oxidative character. 3. Curculigoside possesses potent antioxidant properties against oxidative stress insults. can protect endothelial cells against oxidative injury induced by H2O2, suggesting that this compound may constitute a promising intervention against cardiovascular disorders.

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

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.

Raloxifene (LY-139481) is a selective oestrogen receptor modulator. It has effects on bone and breast cancer and cardiovascular disease risk.

Kinsenoside ((+)-Kinsenoside) shows significant antihepatotoxic, and anti-inflammatory activities. Kinsenoside could be useful for repairing beta cells in pancreatic islet injury as well as improving its function, it could promote the glucose tolerance of acute glucose increase in both diabetic and normal healthy rats. Kinsenoside inhibits osteoclastogenesis from macrophages by attenuating RANKL-induced NF-κB and NFATc1 activities, which in turn, prevents bone loss from OVX mice.

1. Obtusifolin has antioxidant properties and improves chemically induced diabetes and its complications by modulation of oxidative stress. 2. Obtusifolin suppresses phthalate esters-mediated bone resorption, thus may be a novel anti-breast-cancer bone me

Galactosylhydroxylysine hydrochloride, a bone collagen component generated through hydroxylysine's post-translational glycosylation, is liberated during bone resorption. Its levels increase in cases of metabolic bone loss [1].

Mollugin (Rubimaillin) may be a JAK2 inhibitor and inhibits LPS-induced inflammatory responses by blocking the activation of the JAK-STAT pathway. Mollugin as a candidate for a chemotherapeutic agent in OSCCs via the upregulation of the HO-1 and Nrf2 pathways and the downregulation of NF- κ B. Mollugin may be a novel therapeutic candidate for bone loss-associated disorders including osteoporosis, rheumatoid arthritis, and periodontitis. Also, it has anticancer efficacy, can modulate the HER2 pathway in HER2-overexpressing Y cells with a potential role in the treatment and prevention of human breast and ovarian Y with HER2 overexpression.

VEL-0230, also known as NC-2300, is a potent cathespin K inhibitor. VEL-0230 has dual-acting properties that both stimulates bone formation and inhibits loss. VEL-0230 is being studied preclinically for the treatment of diseases involving bone mineral disorders such as bone loss related to multiple myeloma, osteoporosis, bone metastases, and rheumatoid arthritis. Velcura Therapeutics is currently being developed by Velcura Therapeutics. Given VEL- 0230's promotion of bone formation, inhibition of bone loss and reduction of calcium levels, Velcura has chosen Myeloma as its lead indication, as the bone fragility, bone pain, high calcium levels and eventual kidney involvement present serious medical and quality of life issues to affected patients.

15-PGDH-IN-2 (Compound 2) is an inhibitor of 15-PGDH with an IC50 value of 0.274 nM. This compound is useful for research into hair loss, bone formation, gastric ulcer healing, and dermal wound healing [1].

Isoformononetin shows fungitoxic activity against Cladosporium sphaerospermum; it also has immunomodulatory activity, it inhibits the differentiation of Th17 cells and B-cell lymphopoesis to promote osteogenesis in estrogen-deficient bone loss conditions.

Sotatercept (ACE-011), a soluble activin receptor type IIA (ACVR2A) IgG Fc fusion protein, aims to rebalance growth-promoting and inhibiting signaling pathways by targeting activin and growth differentiation factors. This compound shows potential in treating pulmonary arterial hypertension, anemia, bone loss, erythropoiesis, and multiple myeloma (MM) osteolytic lesions [1] [2] [3] [4] [5].

Otenaproxesul (ATB 346) is a novel hydrogen sulphide-releasing derivative of naproxen with markedly reduced toxicity.

6-Raloxifene-β-D-glucopyranoside is a benzothiophene glucuronidated at the 6' position. It is a selective and orally active estrogen receptor antagonist. 6-Raloxifene-β-D-glucopyranoside can be used for inhibiting bone loss, resorption, and lowering lipid

M-5011 is a non-steroidal anti-inflammatory drug and immunomodulator potentially for the treatment of inflammation and pain. M-5011 had an effective antinociceptive activity (ED50 value) of 0.63 mg/kg. M-5011 partially inhibits the generalized bone loss a

1. Dalbergin (6-Hydroxy-7-Methoxy-4-Phenylcoumarin) exhibits similar bone conserving effect against bone-loss as estradiol treatment, it as a therapeutic candidate against postmenopausal osteoporosis. 2. Dalbergin prevents some effects of photoaging and maintain skin integrity by regulating the degradation of the extracellular matrix proteins.

Dehydrodiconiferyl alcohol (DHCA) is a lignan isolated from calabash that inhibits osteoclast differentiation and oophorectomy induced bone loss by acting as an estrogen receptor agonist.

CGP77675 hydrate is an orally active, potent inhibitor of Src family kinases. It inhibits the phosphorylation of peptide substrates and autophosphorylation of purified Src (IC50: 5-20 and 40 nM, respectively), as well as Src, EGFR, KDR, v-Abl, and Lck with IC50s of 0.02, 0.15, 1.0, 0.31, and 0.29 μM, respectively. CGP77675 hydrate may be useful for treating diseases associated with elevated bone loss and has anticancer activity [1].

VnP-16, a synthetic peptide fragment mirroring amino acids 270-281 of vitronectin (a multifunctional glycoprotein involved in cell attachment, migration, and spreading), promotes attachment and spreading of isolated human osteogenic cells. This effect is reversible with β1 integrin siRNA knockdown when VnP-16 is applied at 9.1 µg/cm2 on cell plates. The compound enhances osteogenesis in human skin-derived mesenchymal precursors and MC3T3-E1 mouse calvarial osteoblast precursors. Furthermore, in vivo studies show VnP-16 mitigates IL-1α-induced bone loss, reduces calvarial osteoclast numbers in mice, increases bone mineral density, and lessens trabecular bone loss in a mouse model of ovariectomy-induced bone loss.

ABD-295 is an antiresorptive agent, osteoclast inhibitor, and biphenylsulfide derivative. ABD-295 has potent inhibitory effects on osteoclastic bone resorption in vitro. ABD-295 prevents ovariectomy-induced bone loss in vivo.

Anabolic agent-1 is a novel bone morphogenetic protein-2 up regulator, with the capability of rectifying bone loss in patients and exhibiting versatile clinical applicability.

Thonzonium bromide is a mono-cationic surfactant that is structurally similar to Farnesol as an antimicrobial agent. It inhibits proton transport in a dose-dependent manner (EC50=69 μM). It inhibits RANKL-induced osteoclast formation and bone resorption in vitro and prevents LPS-induced bone loss in vivo.

Astramembrangenin (Cycloastragenol (Astramembrangenin)) is a triterpenoid saponin compound and a hydrolysis product of the main active ingredient in Astragalus membranaceus. Cycloastragenol (CAG) may have a novel therapeutic role in depression

Prostaglandin E2 activates four distinct G protein-coupled receptors, EP1-4. Rivenprost is a potent and selective agonist for the EP4 receptor (Ki = 0.7, 56, 620, and >10,000 nM for EP4, EP3, EP2, and EP1, respectively). It has been used to promote EP4-mediated bone formation, prevent bone loss related to osteoporosis, drive osteoblast differentiation, and stabilize bone implants.[1][2][3][4][5] Rivenprost has also been used to support wound healing.[6]

Dalbergiphenol shows antiosteoporotic activity, dalbergiphenol treatment can effectively prevent OVX-induced increase in bone loss and decrease in bone strength possibly by increasing osteoblastic activities and by decreasing osteoclastic activities.

1. Neobavaisoflavone is isolated as a DNA polymerase inhibitor. 2. Neobavaisoflavone might be a potential anabolic agent to treat bone loss-associated diseases. 3. Neobavaisoflavone has anti-inflammatory activity, can significantly inhibit the production

E197 is a DOCK5 inhibitor. E197 can inhibit both mouse and human osteoclast activity. In particular, E197 prevented pathological bone loss in mice. Most interestingly, treatment with E197 did not affect osteoclast and osteoblast numbers and hence did not impair bone formation. E197 could represent a lead molecule to develop new antiosteoporotic drugs targeting the mechanism of osteoclast adhesion onto the bone.

XVA143, an α β I-like allosteric antagonist, effectively blocks LFA-1-dependent firm adhesion while simultaneously increasing adhesion under shear flow and rolling conditions, both in vitro and in vivo.

Miroestrol is a potent phytoestrogen compound with multifaceted biological effects. It induces a mammogenic effect and demonstrates neuroprotective properties, along with the ability to prevent bone loss in ovariectomized mice. Additionally, Miroestrol has been shown to reduce the risk of cancer [4].