| Size | Price | Stock | Qty |
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| 1mg |
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| 100mg | |||
| Other Sizes |
| Targets |
L873724 targets cathepsin K, a cysteine protease that is primarily expressed in osteoclasts and plays a key role in bone resorption. Cathepsin K degrades collagen type I and other bone matrix proteins, making it a critical enzyme in bone remodeling. L873724 is a potent inhibitor of cathepsin K, with an IC50 of 0.2 nM. The compound shows selectivity for cathepsin K over other cathepsins, with IC50 values of 178 nM for cathepsin S, 264 nM for cathepsin L, and 5239 nM for cathepsin B.
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| ln Vitro |
At IC50 values of 0.2, 178, 264, and 264 for cathepsin K, cathepsin S, cathepsin L, and cathepsin B, respectively, L-873724 (Compound 22) is a strong and specific non-alkaline inhibitor of cathepsin K. 5239 nanometers. Additionally, L-873724 displays IC50 values for Ramos cathepsin S, Hep G2 cathepsin L, and Hep G2 cathepsin B of 95, 1221, and 4807 nM, respectively [1]. L-873724's half-life against rabbit cathepsin K is 0.5 nM [2].
In vitro, L873724 potently inhibits cathepsin K activity, with an IC50 of 0.2 nM. The compound shows selectivity for cathepsin K over cathepsin S (IC50 = 178 nM), cathepsin L (IC50 = 264 nM), and cathepsin B (IC50 = 5239 nM). L873724 is a reversible inhibitor and is non-basic. The compound's inhibitory activity is concentration-dependent, and its selectivity profile makes it a valuable tool for studying cathepsin K function. |
| ln Vivo |
L-873724 has been shown to be non-lysosomal, orally accessible, and efficacious in a model of rhesus monkey bone resorption 1.
In vivo, L873724 has been studied for its potential in the research of osteoporosis and other bone diseases. As an orally bioavailable cathepsin K inhibitor, the compound may reduce bone resorption and prevent bone loss. However, specific in vivo efficacy data are limited in the available literature. L873724 is primarily used as a research tool for studying cathepsin K pharmacology. |
| Enzyme Assay |
The non-cellular assay for L873724 involves measuring its inhibitory activity against cathepsin K using in vitro enzymatic assays. Recombinant human cathepsin K is incubated with a fluorogenic peptide substrate (such as Z-Gly-Pro-Arg-AMC) in the presence of varying concentrations of L873724. The cleavage of the substrate by cathepsin K results in an increase in fluorescence, which is monitored over time. The inhibition of enzymatic activity is calculated, and the IC50 is determined from concentration-response curves.
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| Cell Assay |
The cellular assay for L873724 involves treating osteoclasts or other cells expressing cathepsin K with the compound and measuring its effects on cathepsin K activity and bone resorption. Osteoclasts are differentiated from precursor cells and cultured on bone slices or synthetic substrates. L873724 is added at various concentrations, and bone resorption is measured by the release of calcium or by analyzing the resorption pits. Cathepsin K activity in cell lysates is measured using a fluorogenic substrate.
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| Animal Protocol |
In the in vivo efficacy study, L873724 is administered orally to animal models of osteoporosis, such as ovariectomized rats. Bone mineral density is measured using dual-energy X-ray absorptiometry (DXA) or micro-computed tomography (µCT). Bone turnover markers are measured in serum or urine. The compound's ability to prevent bone loss and reduce bone resorption is assessed.
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| ADME/Pharmacokinetics |
L873724 has a molecular weight of 481.53 and a molecular formula of C₂₃H₂₆F₃N₃O₃S. The compound is soluble in DMSO at 100 mg/mL (ultrasonic). It should be stored as a powder at -20°C, protected from light and moisture. L873724 is orally bioavailable. The compound should be handled with appropriate laboratory safety precautions.
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| Toxicity/Toxicokinetics |
The toxicological profile of L873724 has not been extensively characterized in the published literature. As a cathepsin K inhibitor, it may affect bone remodeling and other proteolytic processes. Comprehensive toxicology data are limited, and L873724 is not approved for clinical use. The compound should be handled with appropriate laboratory safety precautions.
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| References | |
| Additional Infomation |
L873724 is a potent, selective, and orally bioavailable cathepsin K inhibitor that has been used as a research tool to study cathepsin K function. Its high potency (IC50 = 0.2 nM) and selectivity for cathepsin K over other cathepsins make it a valuable tool for investigating the role of cathepsin K in bone resorption and other physiological processes. L873724 is a non-basic, reversible inhibitor. The compound is not approved for clinical use and is strictly a research tool.
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| Molecular Formula |
C23H26F3N3O3S
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|---|---|
| Molecular Weight |
481.531054973602
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| Exact Mass |
481.165
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| CAS # |
603139-12-4
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| PubChem CID |
9913088
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| Appearance |
White to off-white solid powder
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| LogP |
5.867
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
33
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| Complexity |
785
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| Defined Atom Stereocenter Count |
2
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| SMILES |
CC(C)C[C@@H](C(=O)NCC#N)N[C@@H](C1=CC=C(C=C1)C2=CC=C(C=C2)S(=O)(=O)C)C(F)(F)F
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| InChi Key |
VYFDSJLOCIGIKP-SFTDATJTSA-N
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| InChi Code |
InChI=1S/C23H26F3N3O3S/c1-15(2)14-20(22(30)28-13-12-27)29-21(23(24,25)26)18-6-4-16(5-7-18)17-8-10-19(11-9-17)33(3,31)32/h4-11,15,20-21,29H,13-14H2,1-3H3,(H,28,30)/t20-,21-/m0/s1
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| Chemical Name |
(2S)-N-(cyanomethyl)-4-methyl-2-[[(1S)-2,2,2-trifluoro-1-[4-(4-methylsulfonylphenyl)phenyl]ethyl]amino]pentanamide
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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) |
DMSO : ~100 mg/mL (~207.67 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.19 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.19 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.19 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0767 mL | 10.3836 mL | 20.7671 mL | |
| 5 mM | 0.4153 mL | 2.0767 mL | 4.1534 mL | |
| 10 mM | 0.2077 mL | 1.0384 mL | 2.0767 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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