奧當(dāng)卡替作用機(jī)制 - Medchemexpress - MCE中國

1、Product Data SheetOdanacatibCat. No.: HY-10042CAS No.: 603139-19-1分式: CHFNOS分量: 525.56作靶點: Cathepsin作通路: Metabolic Enzyme/Protease儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 25 mg/mL (47.57 mM)* means soluble, but saturation unknown.SolventMass1 mg 5 mg 10

2、mgConcentration制備儲備液1 mM 1.9027 mL 9.5137 mL 19.0273 mL5 mM 0.3805 mL 1.9027 mL 3.8055 mL10 mM 0.1903 mL 0.9514 mL 1.9027 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 儲存時，請在 6 個內(nèi)使，-20C 儲存時，請在 1 個內(nèi)使。體內(nèi)實驗 請根據(jù)您的實驗動物和給藥式選擇適當(dāng)?shù)娜芙獍?。以下溶解案都請先按?In Vitr

3、o 式配制澄清的儲備液，再依次添加助溶劑：為保證實驗結(jié)果的可靠性，澄 的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實驗的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天 使； 以下溶劑前顯的百分 指該溶劑在您配制終溶液中的體積占；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可 以通過加熱和/或超聲的式助溶1. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (4.76 mM); Clear solution此案可獲得 2.5 mg/mL (4.76 mM，飽和度未知) 的澄 溶液，此案不適于實驗周 期在半個以上的實驗。以 1 mL 作液為例，取 100 L 25.0 mg

4、/mL 的澄 DMSO 儲備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITYPage 1 of 2 www.MedChemE物活性 Odanacatib (MK-0822)有效，選擇性的組織蛋酶K抑制劑，IC50 分別為0.2 nM 和 1 nM。IC & Target IC50: 0.2 nM (Human Cathepsin K), 1 nM (Rabbit Cathepsin K)體外研究 Odanacatib is a weak inhibitor of antigen presentation, measured in a mouse B cell line

5、 (IC50=1.50.4 M),compared to the Cat S inhibitor LHVS (IC50=0.001 M) in the same assay. Odanacatib also shows weak inhibition ofthe processing of the MHC II invariant chain protein Iip10 in mouse splenocytes compared to LHVS (minimuminhibitory concentration 1-10 M versus 0.01 M, respectively)1. Odan

6、acatib reduces resorption activity asmeasured by CTx release (IC50=9.4 nM) or resorption area (IC50=6.5 nM), but has no impact on OC activation.Odanacatib dose-dependently reduces CTx release with an IC50=9.41.0 nM. Odanacatib treated OC accumulateslabeled degraded bone matrix proteins in CatK conta

7、ining vesicles2.體內(nèi)研究 Odanacatib (30 mg/kg, orally, once daily) persistently suppresses bone resorption markers and serum boneformation markers versus vehicle-treated OVX monkeys. Odanacatib displays compartment-specific effects ontrabecular versus cortical bone formation, with treatment resulting in

8、 marked increases in periosteal bone formationand cortical thickness in ovariectomized monkeys whereas trabecular bone formation is reduced3. The bonevolume/total volume (BV/TV) and bone mineral density (BMD) of the OVX + ODN-h group is significantly higherthan that of the OVX + Veh group (p 0.05).

9、The expressions of Runx2, Collagen-1, BSP, Osterix, OPN and SPP1 aresignificantly lower in the OVX + ODN-h group than in the OVX + Veh group (p 0.01). Compared with the OVX +Veh group, the expressions of Collagen-I, BSP, Osterix, OPN and ALP reduce in the OVX + ODN-l group, but areupregulated in the

10、 OVX + ODN-h group4.PROTOCOLCell Assay 2 To assess cell survival, differentiated osteoclast (OC) at appr 7104 cells/cm2 are re-seeded on bovine bone sliceswith or without 100 nM Odanacatib (ODN). Bone slices are fixed on days 2, 4, 6, and 12 with no media changes.Samples are stained for TRAP activit

11、y, and OC number.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Sixteen, 8-month-old, female Sprague-Dawley (SD) rats (weight, 385 55 g) are given water and soft diet food adAdministration 4 libitum in a temperature-controlled environment with r

12、egular 12-h cycles of light and dark. The rats are randomisedinto 4 groups, with 4 rats in each group: sham group, OVX + Veh group, OVX + ODN-l group and OVX + ODN-hgroup. Following implant insertion, Odanacatib (ODN, 5 mg/mL) is administered to the OVX + ODN-l and OVX +ODN-h groups at concentration

13、s of 1 mL/kg and 6 mL/kg, respectively, by gavaging once a day for 8 weeks. The OVX+ Veh group is gavaged with 0.5% sodium carboxymethyl cellulose at a concentration of 6 mL/kg over the sameduration. After the gavage administration, the rats of each group are sacrificed by injecting sodium pentobarb

14、italintravenously. The implants are harvested and fixed in 10% buffered formalin together with the surrounding bone.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Biochem Biophys Res Commun. 2015 Jun 26;462(2):159-64.See more customer valid

15、ations on HYPERLINK www.MedChemE www.MedChemEREFERENCESPage 2 of 3 www.MedChemE1. Jacques Yves Gauthier, et al. The discovery of odanacatib (MK-0822), a selective inhibitor of cathepsin K. Bioorg Med Chem Lett. 2008 Feb 1;18(3):923-8.2. Leung P, et al. The effects of the cathepsin K inhibitor odanac

16、atib on osteoclastic bone resorption and vesicular trafficking. Bone. 2011 Oct;49(4):623-635.3. Ng KW. Potential role of odanacatib in the treatment of osteoporosis. Clin Interv Aging. 2012;7:235-47.4. Yi C, et al. Inhibition of cathepsin K promotes osseointegration of titanium implants in ovariectomised rats. Sci Rep.