| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
MK-0674 targets cathepsin K, a cysteine protease that plays a critical role in bone resorption by degrading the organic matrix of bone. Cathepsin K is primarily expressed in osteoclasts and is responsible for the degradation of type I collagen and other bone matrix proteins. By inhibiting cathepsin K, MK-0674 reduces bone resorption activity, making it a potential therapeutic agent for osteoporosis. The compound has an IC50 of 0.4 nM for cathepsin K and is highly selective over other cathepsins.
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| ln Vitro |
Compound 13, MK-0674, has an IC50 of 10 nM and a strong influence on rabbit osteoclasts' ability to resorb bone [1].
In vitro, MK-0674 demonstrates potent inhibition of cathepsin K with an IC50 of 0.4 nM. The compound shows high selectivity over other cathepsins, with 1156-fold selectivity over cathepsin B, 1465-fold over cathepsin F, 11857-fold over cathepsin L, and 243-fold over cathepsin S. It acts on rabbit osteoclasts with an IC50 of 10 nM. This high potency and selectivity profile make MK-0674 a valuable tool for studying the role of cathepsin K in bone biology. |
| ln Vivo |
In vivo, MK-0674 is orally bioavailable, allowing for effective administration via the oral route. As a cathepsin K inhibitor from the same structural class as odanacatib, it is expected to have comparable in vivo efficacy in reducing bone resorption. Specific in vivo efficacy data from animal models (such as ovariectomized rat models of osteoporosis) are not detailed in the available sources. The compound is used in research related to bone metabolism and osteoporosis.
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| Enzyme Assay |
The cathepsin K inhibition assay for MK-0674 involves incubating the compound with recombinant human cathepsin K and a fluorogenic peptide substrate (such as Z-Leu-Arg-AMC or a related substrate). The reaction is carried out in a cathepsin assay buffer (e.g., 100 mM sodium acetate, pH 5.5, containing 2 mM DTT and 5 mM EDTA) at 37°C for a specified time. The release of AMC fluorescence is measured at excitation 355 nm and emission 460 nm. IC50 values are calculated from dose-response curves. Selectivity is assessed by testing against other cathepsins (B, F, L, S).
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| Cell Assay |
To evaluate the cellular activity of MK-0674, osteoclasts can be differentiated from primary bone marrow macrophages or RAW 264.7 cells using RANKL and M-CSF. Mature osteoclasts are plated on bone or dentin slices and treated with varying concentrations of MK-0674. After incubation, the resorption pit area is measured to assess the compound's ability to inhibit bone resorption activity. Alternatively, cathepsin K activity in osteoclast lysates can be measured using a fluorogenic substrate. Cell viability is monitored to ensure that observed effects are not due to cytotoxicity.
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| Animal Protocol |
The in vivo efficacy of MK-0674 would typically be evaluated in ovariectomized (OVX) rat or mouse models of osteoporosis. Female rodents undergo ovariectomy to induce estrogen deficiency and bone loss. Animals are then treated with MK-0674 orally at various doses for a period of several weeks. Bone mineral density (BMD) is measured using dual-energy X-ray absorptiometry (DXA) or micro-computed tomography (μCT). Bone turnover markers (such as CTX-1 and P1NP) are measured in serum. Bone histomorphometry is performed to assess bone resorption parameters. Specific protocols are not detailed in the available sources.
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| ADME/Pharmacokinetics |
MK-0674 is characterized as being orally bioavailable. Specific pharmacokinetic parameters (e.g., Cmax, Tmax, half-life, AUC) are not detailed in the available sources. The compound has a molecular weight of 527.5 and a molecular formula of C26H27F6N3O2. It is a small molecule with properties suitable for oral administration. As a cathepsin K inhibitor from the same structural class as odanacatib, it is expected to have favorable pharmacokinetic properties.
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| Toxicity/Toxicokinetics |
Specific toxicity data for MK-0674 are not provided in the available sources. As a research compound, it is intended for laboratory use only and is not approved for human therapeutic applications. The compound is a potent and selective cathepsin K inhibitor from the same structural class as odanacatib. Standard safety precautions should be followed when handling this compound, including the use of appropriate personal protective equipment.
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| References | |
| Additional Infomation |
MK-0674 is a potent, orally bioavailable, and selective cathepsin K inhibitor with an IC50 of 0.4 nM. It shows 1156-fold selectivity over cathepsin B, 1465-fold over cathepsin F, 11857-fold over cathepsin L, and 243-fold over cathepsin S. It is from the same structural class as odanacatib with a comparable inhibitory potency profile against cathepsin K. The compound acts on rabbit osteoclasts with an IC50 of 10 nM. It is used in research related to bone metabolism and osteoporosis.
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| Molecular Formula |
C26H27F6N3O2
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| Molecular Weight |
527.501907587051
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| Exact Mass |
527.201
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| CAS # |
887781-62-6
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| PubChem CID |
16666183
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
6.306
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
37
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| Complexity |
822
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| Defined Atom Stereocenter Count |
3
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| SMILES |
FC(C)(C)C[C@@H](C(NC1(C#N)CC1)=O)N[C@H](C(F)(F)F)C1C=CC(C2C=CC([C@H](C(F)F)O)=CC=2)=CC=1
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| InChi Key |
YTEORGORWDMMRK-HBMCJLEFSA-N
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| InChi Code |
InChI=1S/C26H27F6N3O2/c1-24(2,29)13-19(23(37)35-25(14-33)11-12-25)34-21(26(30,31)32)18-9-5-16(6-10-18)15-3-7-17(8-4-15)20(36)22(27)28/h3-10,19-22,34,36H,11-13H2,1-2H3,(H,35,37)/t19-,20+,21-/m0/s1
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| Chemical Name |
(S)-N-(1-cyanocyclopropyl)-2-(((S)-1-(4'-((R)-2,2-difluoro-1-hydroxyethyl)-[1,1'-biphenyl]-4-yl)-2,2,2-trifluoroethyl)amino)-4-fluoro-4-methylpentanamide
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| Synonyms |
MK0674; MK 0674; MK-0674
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8957 mL | 9.4787 mL | 18.9573 mL | |
| 5 mM | 0.3791 mL | 1.8957 mL | 3.7915 mL | |
| 10 mM | 0.1896 mL | 0.9479 mL | 1.8957 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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