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    Bone is a rigid tissue that performs several key functions: it supports the body; it provides a point of attachment for tendons; it protects the internal organs; it produces blood cells; and it stores key minerals such as calcium and phosphorus. Throughout life, bone is remodeled by the activity of osteoblasts and osteoclasts. Osteoblasts are responsible for the synthesis of bone, while osteoclasts resorb bone tissue. A carefully controlled balance of these activities underlies bone remodeling and an imbalance can result in disorders such as osteoporosis, which weakens bones.

    Osteoblasts and Osteoclasts

    Osteoblasts and osteoclasts are derived from different cell precursors - mesenchymal and hematopoietic stem cells (MSCs and HSCs), respectively. Differentiation of HSCs to osteoclasts involves a number of cytokines such as bone morphogenetic protein (BMP) and TNF-α. Rho kinase (ROCK) inhibition may also stimulate osteoblast differentiation. Osteoblasts and osteoclasts are responsible for bone repair and growth, as well as the maintenance of bone density.

类风湿关节炎和骨质疏松症的炎症相关发病机理。 在发炎的类风湿滑膜和骨骼组织中,由募集的炎性细胞(巨噬细胞,T细胞和B细胞),内皮细胞和滑膜成纤维细胞产生的促炎细胞因子是类风湿关节炎和骨质疏松症炎症过程的核心。 这种病理过程还涉及先天性和适应性免疫反应。 这些促炎性细胞因子导致滑膜成纤维细胞活化并产生导致组织破坏的蛋白酶。 另外,破骨细胞的细胞因子触发活化和分化在骨质流失中很重要。 类黄酮通过减少炎症细胞的募集,细胞因子的产生,MMP的表达以及破骨细胞的活化或分化来发挥作用。

   Metabolic Bone Disease

   Loss of bone density normally occurs after the age of 35, and is a natural part of ageing. Bone turnover is regulated by a number of factors, including estrogen, nitric oxide and calcium-regulated calcium channels. However, bone loss may also be a result of metabolic bone disease, a term that describes a number of disorders resulting from mineral abnormalities in bone tissue. These include osteoporosis, Paget's disease of bone, osteomalacia and rickets.

    Osteoporosis is relatively common, particularly in post-menopausal women, and can result in an increased likelihood of bone fracture. Osteomalacia and rickets describe deficiencies in bone mineralization in adults and children, respectively. Paget's disease of bone results from increased bone resorption by osteoclasts, followed by rapid, disorganized bone deposition by osteoblasts. The resulting tissue is larger and weaker than normal bone.

Cat. No. Product Name CAS No. Information

Alendronate sodium hydrate


Alendronate sodium hydrate (Alendronate;MK 217;G-704650 Adronat) is a bisphosphonate that acts as a specific inhibitor of osteoclastmediated bone resorption, inhibits osteoclast protein-tyrosine phosphatase (PTPepsilon) with IC50 of 2 uM; also inhibits the activities of other bacterially expressed PTPs such as PTPsigma and CD45, suppresses in vitro formation of multinucleated osteoclasts from osteoclast precursors and in vitro bone resorption by isolated rat osteoclasts with IC50 of 10 uM; also is also inhibits farnesyl disphosphate synthase with IC50 of 1.7 uM.




Relacatib (SB-462795, GSK-462795) is a potent and orally bioavailable small molecule cathepsin inhibitor with Ki of 41, 68 and 53 pM for cathepsin K, L and V, respectively; displays 39-300-fold selectivity over other cathepsins; inhibits endogenous cathepsin K in situ in human osteoclasts and human osteoclast-mediated bone resorption with IC50 of 45 nM and 70 nM, respectively; inhibits bone resorption both in vitro in human tissue and in vivo in cynomolgus monkeys.


L 873724


L 873724 is a potent and selective non-basic cathepsin K inhibitor with IC50 of 0.2 nM, shows no significant potency against Cat B, L, and S (IC50= 5239, 264, and 178 nM); demonstrates excellent pharmacokinetics and efficacy in an ovariectomized (OVX) rhesus monkey model.




A potent, selective, orally active inhibitor of cathepsin K with Ki of 0.1 nM, 0.049 nM and 0.85 nM for human, rabbit and rat cathepsin K, respectively; shows less or no potentcy for human cathepsin S/L/B/C (Ki=0.83/1.7/32/2500 nM); inhibits human osteoclasts bone resorption in vitro at a concentration more than 100 fold lower than that of alendronate; reduces plasma calcium level increased by PTHrP in thyroparathyroidectomized rats, decreases serum and urine C-telopeptide of type I collagen level.




Odanacatib is a potent, selective, reversible and orally active cathepsin K inhibitor with IC50 of 0.2 nM; displays >300-fold selectivity over cathepsin B, L, S, F, and V; demonstrates the potentiation for the treatment of osteoporosis and other skeletal disorders associated with excessive bone remodeling.


Ronacaleret hydrochloride


Ronacaleret hydrochloride is a potent calcium sensing receptor (CaSR) negative allosteric modulator with IC50 of 146 nM for hCaSR; stimulates parathyroid hormone (PTH) release and increases bone formation markers; act as an effective oral anabolic agent to enhance fracture healing.




Ronacaleret is a potent calcium sensing receptor (CaSR) negative allosteric modulator with IC50 of 146 nM for hCaSR; stimulates parathyroid hormone (PTH) release and increases bone formation markers; act as an effective oral anabolic agent to enhance fracture healing.




LGD-2226 (LGD2226) is an orally active, selective androgen receptor modulator (SARM) with binding Ki of 1 nM, >1000-fold selectivity over GR,PR, MR and ER; LGD2226 is fully active in cell-based models of bone and muscle, exhibits anabolic activity on muscle and bone with reduced impact on prostate growth in rodent models; LGD2226 is also efficacious in a sex-behavior model in male rats measuring mounts, intromissions, ejaculations, and copulation efficiency.

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