bone cancer

Lumiracoxib (Prexige) is a novel, selective COX-2 inhibitor with IC50 and Ki of 0.14 μM and 0.06 μM, exhibits 515-fold selectivity over COX-1. Phase 4.

(-)-Epigallocatechin Gallate (EGCG) is a phenolic antioxidant polyphenol flavonoid found in plants such as green and black tea, which inhibits telomerase and DNA methyltransferase, blocks the activation of EGF receptors and HER-2 receptors, inhibits cellular oxidation, and prevents free radical damage to cells.

Cyclophosphamide is an alkylating agent type of anti-tumor drug, and its main target is DNA. Cyclophosphamide inhibits the proliferation of tumor cells by undergoing alkylation reactions with DNA, interfering with the replication and transcription processes of DNA.

MBC-11 is a first-in-class conjugate of the bone-targeting bisphosphonate etidronate covalently linked to the antimetabolite cytarabine (araC), with potential to treat tumor-induced bone disease (TIBD).

CID-5056270 has anticancer activity and can inhibit lung cancer, anal cancer, bladder cancer, cervical cancer, vulvar cancer, penile cancer, Burkitt's lymphoma, breast cancer and bone cancer. It can be used to study hypertension, Alzheimer's disease and arteriosclerosis.

ERG240 is an inhibitor of branched-chain amino acid aminotransferase 1 (BCAT1). ERG240 can be used for the research of rheumatoid arthritis, cancer, and bone disease.

1. Isoquercetin (3-Glucosylquercetin) is a potential stimulator of bone mineralization used for prophylaxis of osteoporotic disorders. 2. Isoquercetin may be as a potential therapeutic agent against neurodegeneration in Parkinson's disease. 3. Isoquercetin is an inhibitor of Wnt/β-catenin and may be as a potential novel anti-tumoral agent, such as against human pancreati,liver cancer related to opioid receptors and to the activation of the mitogen-activated protein kinase (MAPK) signalling pathway. .

(-)-(S)-Equol (4',7-Dihydroxyisoflavan) is an orally bioavailable, non-steroidal estrogen naturally produced by the metabolism of the isoflavonoid daidzein by human intestinal microflora, with potential chemoprotective and estrogen receptor (ER) modulating activities. S-equol preferentially binds to and activates the beta isoform of ER in certain target tissues, while having an antagonistic effect in other tissues. This modulates the expression of ER-responsive genes in a tissue-specific manner. This agent may increase bone mineral density, affect vasomotor symptoms, and may decrease the proliferation rate of susceptible cancer cells. In addition, this agent interferes with the activity of enzymes involved in steroid biosynthesis. S-equol inhibits dihydrotestosterone (DHT) production and may inhibit the proliferation of androgen-driven prostate cancer. S-equol is the biologically active enantiomer while R-equol is essentially inactive and has a weak affinity for alpha-ER.

Zoledronic Acid (ZOL 446) is a bisphosphonate. Zoledronic Acid (ZOL 446) is used to prevent skeletal fractures in patients with cancers such as multiple myeloma and prostate cancer. It can also be used to treat hypercalcemia of malignancy and can be helpful for treating pain from bone metastases. An annual dose of Zoledronate may also prevent recurring fractures in patients with a previous hip fracture. Zoledronic Acid (ZOL 446) is a single 5 mg infusion for the treatment of Paget's disease of bone. In 2007, the FDA also approved Reclast for the treatment of postmenopausal osteoporosis.

Soy Isoflavone is extracted from the seeds of leguminous plants. The isoflavones in soybeans are natural phytoestrogens, which have good medicinal value and can reduce the incidence of breast cancer in women, relieve menopausal symptoms, and increase bone density.

Pipobroman (Vercyte) is an anti-cancer drug that probably acts as an alkylating agent. Pipobroman has well documented clinical activity in polycythemia vera (PV) and essential thrombocythemia (ET). Pipobroman allows, within 3 months, to attain a response in more than 90% of patients, without clinically relevant toxicities. The 10-years risk of thrombosis of patients treated with Pipobroman is about 15%, The anti-proliferative activity of Pipobroman on bone marrow megakaryocytes seems of particular value in lowering the occurrence of post-PV and post-ET MMM, whose risk is the lowest registered with available treatments. The 10-year risk of acute leukemia with Pipobroman is 5% in PVand 3% in ET, which is only slightly higher than that expected as a natural evolution of the disease. In conclusion, the use of Pipobroman is a definite alternative to hydroxyurea in patients with PV and ET at high risk of thrombosis.

KM02894 is a glutamate release inhibitor. Cancer cells release high levels of glutamate that can disrupt normal bone turnover, which can lead to cancer-induced bone pain.KM02894 may be used in the study of tumor-related diseases.

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

Raloxifene (LY139481) is a selective estrogen receptor modulator that exhibits both estrogen agonist and antagonist activities at certain sites, with antiviral activity against viruses like Ebola, influenza, and HCV, useful for studying viral infections.

CSF1R-IN-18 (Compound 16t) is an aniline derivative that acts as an inhibitor of the colony stimulating factor 1 receptor (CSF1R). It is applicable in research related to cancer, central nervous system disorders, and bone diseases.

DMH2 is an antagonist of bone morphogenetic protein (BMP) type I receptor. It acts by decreasing growth and inducing cell death of lung cancer cell lines.

Hepln-13 is a hepsin inhibitor that acts by hindering prostate cancer bone metastasis.

Mitolactol is an alkylating antineoplastic toxic to bone marrow; utilized in breast cancer, also in combination with other drugs. Mitolactol is able to cross bloodbrain barrier, consequently could control certain brain tumors.

Incadronate Disodium is a bone resorption inhibitor. Incadronate disodium inhibits macrophage migration to site of inflammation in vivo and proliferation and causes apoptosis in cancer cells in vitro.

p-SCN-Bn-HOPO is an excellent bifunctional chelating agent for (89)Zr ImmunoPET, with low background, good tumor-organ contrast, and importantly, very low bone uptake for BT474 breast cancer imaging.

Neuromedin U (NMU) is a neuropeptide first demonstrated to drive smooth muscle contraction.1Translated as a 174 amino acid propeptide, NMU is cleaved to different lengths in different animals. It has diverse receptor-mediated rolesin vivo, as it regulates feeding, vasoconstriction, nociception, and bone remodeling and contributes to obesity, cancer and septic shock.2,2NMU-25 is the active form of NMU in humans. It binds with high affinity to receptors on human left ventricle and coronary artery (KDs = 0.26 and 0.11 nM, respectively), eliciting endothelium-independent vasoconstriction.3NMU-25 also suppresses glucose-stimulated insulin secretion in human islets, and this effect is lost in NMU R165W mutants, resulting in early-onset obesity.4 1.Mitchell, J.D., Maguire, J.J., and Davenport, A.P.Emerging pharmacology and physiology of neuromedin U and the structurally related peptide neuromedin SBritish Journal of Pharmacology15887-103(2009) 2.Greenwood, H.C., Bloom, S.R., and Murphy, K.G.Peptides and their potential role in the treatment of diabetes and obesityRev.Diabet.Stud.8(3)355-368(2011) 3.Mitchell, J.D., Maguire, J.J., Kuc, R.E., et al.Expression and vasoconstrictor function of anorexigenic peptides neuromedin U-25 and S in the human cardiovascular systemCardiovascular Research81353-361(2009) 4.Alfa, R.W., Park, S., Skelly, K.R., et al.Suppression of insulin production and secretion by a decretin hormoneCell Metabolism21(2)323-333(2015)

Osteocalcin (1-49) is a non-collagenous peptide that is secreted by osteoblasts and odontoblasts and comprises 1-2% of the total protein in bone. Secretion of osteocalcin (1-49) is stimulated by 1,25-dihydroxy vitamin D and plasma levels increase in diseases that induce dysregulated bone turnover such as osteoporosis, Paget's disease, and primary hyperparathyroidism. Osteocalcin (1-49) is positively correlated with insulin sensitivity and negatively correlated with high blood glucose levels in women. In vitro, osteocalcin induces chemotaxis of MDA-MB-231 breast cancer cells, human peripheral blood monocytes, and rat osteosarcoma cells with osteoblast-like characteristics. It is also expressed by vascular smooth muscle cells (VSMCs) displaying an osteoblast-like phenotype and has been positively associated with calcification of aortic tissue and heart valves in humans.

17β-hydroxy Exemestane is the primary active metabolite of exemestane . It is formed by metabolism of exemestane by the cytochrome P450 (CYP) isoforms CYP1A and CYP4A11. 17β-hydroxy Exemestane is an aromatase inhibitor (IC50 = 69 nM using human placental microsomes) and an androgen receptor (AR) agonist (IC50 = 39.6 nM) that is selective for AR over estrogen receptor α (ERα; IC50 = 21.2 μM). It stimulates growth of AR- and ERα-positive MCF-7 (EC50 = 2.7 μM) and T47D breast cancer cells (EC50s = 0.43 and 1,500 nM for AR- and ER-mediated growth, respectively) and inhibits proliferation of testosterone-treated aromatase-overexpressing MCF-7aro cells in a concentration-dependent manner. 17β-hydroxy Exemestane (20 mg/kg) inhibits increases in serum cholesterol and LDL levels and prevents decreases in bone mineral density in the lumbar vertebrae and femur, as well as femoral bending strength and compressive strength of the fifth lumbar vertebrae, in ovariectomized rats.

JAK2 inhibitor (IC50 = 397 nM). Also inhibits STAT3 and STAT5 phosphorylation. Inhibits cell growth and induces apoptosis in cells expressing the JAK2V617F mutation. Manshouri et al (2011) Bone marrow stroma-secreted cytokines protect JAK2(V617F)-mutated cells from the effects of a JAK2 inhibitor. Cancer Res. 71 3831 PMID:21512135 |Quintás-Cardama et al (2011) Preclinical characterization of atiprimod, a novel JAK2 AND JAK3 inhibitor. Invest.New Drugs 29 818 PMID:20372971