Odanacatib

製品コードS1115 バッチS111501

印刷

化学情報

Chemical Structure Synonyms MK-0822 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C25H27F4N3O3S
分子量 525.56 CAS No. 603139-19-1
Solubility (25°C)* 体外 DMSO 105 mg/mL (199.78 mM)
Ethanol 3 mg/mL (5.7 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Odanacatib is a potent, selective, and neutral inhibitor of cathepsin K (human/rabbit) with IC50 of 0.2 nM/1 nM, and demonstrated high selectivity versus off-target cathepsin B, L, S. Phase 3.
in vitro In vitro, Odanacatib shows the high inhibitory activity and selectivity on cathepsin K with IC50 values of 0.2 nM and 1 nM for human cathepsin K and rabbit cathepsin K, respectively. Furthermore, Odanacatib also shows similar potencies in whole human cell enzyme occupancy assays with corrected IC50 of 5 nM. [1] A recent study shows that Odanacatib results in reduction of Osteoclast (OC) resorption activity by interrupting intracellular vesicular trafficking. [2]
in vivo In preclinical rats, Odanacatib (10 mg/kg) exhibits excellent pharmacokinetics with clearance (Cl: 2 mL kg-1 min-1), low volume of distribution (Vdss: 1.1 L kg-1), half-life (T1/2: 6 hours) and oral bioavailability (F: 8%), respectively. Besides, Odanacatib also exhibits excellent metabolic stability in rat hepatocytes with a 96% recovery of the parent identity. [1] Odanacatib (ODN) administrated by p.o. prevents bone loss in ovariectomized (OVX) rabbits in a dose-related manner. Moreover, Odanacatib (9 µM/day) leads to a significant increase in proximal femur bone mineral density (BMD) (7.8%), femoral neck BMD (10.8%) and the greater trochanter BMD (6.5%). [3] In the estrogen-deficient, skeletally mature rhesus monkeys, long-term treatment with Odanacatib effectively inhibits bone turnover without reducing osteoclast number and maintains normal biomechanical properties of the spine of OVX nonhuman primates. [4]
特徴 A potent, selective, and neutral cathepsin K inhibitor.

プロトコル(参考用のみ)

キナーゼアッセイ Enzyme Inhibition [1]
To measure enzyme activity, assays are carried out in 50 mM MES pH 5.5 containing 2.5 mM DTT, 2.5 mM EDTA, and 10% DMSO. IC50 values of Odanacatib are determined for human cathepsins K and for humanized rabbit cathepsin K using 2 μM of Z-Leu-Arg-AMC as substrate. Prior to the addition of substrate, different concentrations of the inhibitor Odanacatib ranging from 100 μM to 0.2 nM are preincubated for 15 minutes with each enzyme (0.2 nM−1 nM) to allow the establishment of the enzyme−inhibitor complex. Substrate is then added and the enzyme activity measured fro the increase of fluorescence at 460 nm (λex = 355 nm). The final volume of the reaction is 100 uL. Assays are performed in 96-well plate format and the plate read using a Spectramax plate reader. The percent inhibition of the reaction is calculated from a control reaction containing only vehicle. IC50 curves are generated by fitting percent inhibition values to a four parameter logistic model.
動物実験 動物モデル Ovariectomized (OVX) rabbit model
投薬量 ≤9 µM/day
投与方法 Administered via p.o.

カスタマーフィードバック

Data independently produced by , , Shandong University, 2014, Craniofacial Science.

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Oral microbial extracellular DNA initiates periodontitis through gingival degradation by fibroblast-derived cathepsin K in mice [ Commun Biol, 2022, 5(1):962] PubMed: 36104423
The abnormal accumulation of heparan sulfate in patients with mucopolysaccharidosis prevents the elastolytic activity of cathepsin V [ Carbohydr Polym, 2021, 253:117261] PubMed: 33278943
The CD200-CD200R axis promotes squamous cell carcinoma metastasis via regulation of cathepsin K [ Cancer Res, 2021, canres.3251.2020] PubMed: 34183355
Development of potent and selective inhibitors targeting the papain-like protease of SARS-CoV-2 [ Cell Chem Biol, 2021, S2451-9456(21)00213-0] PubMed: 33979649
Identification of Required Host Factors for SARS-CoV-2 Infection in Human Cells [ Cell, 2020, S0092-8674(20)31394-5] PubMed: 33147445
Inappropriate cathepsin K secretion promotes its enzymatic activation driving heart and valve malformation [ JCI Insight, 2020, 5(20)133019] PubMed: 33055423
Cathepsin K regulates localization and secretion of Tartrate-Resistant Acid Phosphatase (TRAP) in TRAP-overexpressing MDA-MB-231 breast cancer cells. [ BMC Mol Cell Biol, 2020, 21(1):15] PubMed: 32188406
A Mild Inhibition of Cathepsin K Paradoxically Stimulates the Resorptive Activity of Osteoclasts in Culture [ Calcif Tissue Int, 2019, 104(1):92-101] PubMed: 30194476
Down-regulation of cathepsin S and matrix metalloproteinase-9 via Src, a non-receptor tyrosine kinase, suppresses triple-negative breast cancer growth and metastasis. [ Exp Mol Med, 2018, 50(9):118] PubMed: 30185799
Tanshinones that selectively block the collagenase activity of cathepsin K provide a novel class of ectosteric antiresorptive agents for bone. [ Br J Pharmacol, 2018, 175(6):902-923] PubMed: 29278432

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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