| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
Cathepsin K (CTSK), Cathepsin L (CTSL), Cathepsin V (CTSV). Relacatib is a potent inhibitor of these cysteine proteases, with highest affinity for cathepsin K (Ki = 41 pM). Cathepsin K is the primary protease responsible for bone matrix degradation during osteoclast-mediated bone resorption, making it an attractive target for anti-resorptive therapy.
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| ln Vitro |
In vitro biological activity was reported when human osteoclastoma-derived osteoclasts were injected on bovine cortical bone slices and then Relacatib was incubated. For human cathepsin K and L, it exhibited an inhibitory action with a Ki value of 0.041 nM. The experiment yielded cathepsin V, cathepsin S, and cathepsin B concentrations of 0.068 nM, 0.063 nM, 1.6 nM, and 13 nM, respectively [1]. Relacatib exhibits activity against the monkey cathepsins K, L, V, and B, with corresponding Ki values of 0.041 nM, 0.28 nM, 0.72 nM, and 11 nM. Relacatib has a Ki value of 0.20 nM against mouse cathepsin L and 0.17 nM against rat cathepsin L, respectively [2].
In vitro, Relacatib demonstrates potent inhibition of human cathepsins K, L, and V with Ki values of 41 pM, 68 pM, and 53 pM, respectively. The compound inhibits bone resorption in human tissue explant models. Its high potency and selectivity for cathepsin K over other proteases make it an effective tool for studying the role of cathepsin K in bone metabolism. |
| ln Vivo |
The T1/2, CL, or Vdss of male Sprague rats are 109 minutes, 19.5 mL/min/kg, or 1.86 in the case of relacib (1-2 mg/kg IV over 0.5 hours; 2-4 mg/kg PO as bolus gavage). In the PK iv/po crossover research, the corresponding values for Dawley rats and monkeys were 168 minutes, 11.7 mL/min/kg, and 1.79 L/kg, respectively. Relacatib's oral bioavailability in rats is 89.4%, but in monkeys it is 28% [1]. Blood samples were taken 1.5, 4, 24, 48, and 72 hours after dosage, and SB-462795 (subcutaneous injection; 12 mg/kg) effectively suppressed two markers of bone resorption, N-(NTx) and type I assessed in serum Collagen C-telopeptide (CTx). With the exception of the 48-hour time point, when serum osteocalcin, a biomarker of osteoblast activity, was significantly lower (42% below baseline, while the vehicle was 18% lower than baseline), there was no change in serum osteocalcin levels between animals treated with SB-462795 and those given with vehicle [2].
In vivo, Relacatib inhibits bone resorption in cynomolgus monkeys. The compound is orally bioavailable and demonstrates anti-resorptive activity in preclinical models of osteoporosis. By inhibiting cathepsin K, Relacatib reduces excessive bone turnover without affecting bone formation, offering a potentially distinct mechanism from bisphosphonates. Its efficacy in non-human primates supported its progression into clinical development. |
| Enzyme Assay |
Cell-free enzyme assays for Relacatib use recombinant human cathepsins K, L, and V and fluorogenic peptide substrates (e.g., Z-Leu-Arg-AMC for cathepsin K). The compound is incubated with the enzyme and substrate at varying concentrations (0.001-10000 nM) for 15-60 minutes at 37°C in appropriate buffer (pH 5.5 for cathepsin K). Substrate cleavage is monitored by fluorescence at excitation/emission wavelengths of 360/460 nm. Ki values are calculated from dose-response curves using appropriate kinetic models. Selectivity profiling is performed against a panel of related proteases.
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| Cell Assay |
Cellular assays for Relacatib use osteoclasts differentiated from human peripheral blood mononuclear cells or from RAW 264.7 macrophages. Cells are cultured on bone slices or dentin slices and treated with Relacatib at concentrations ranging from 0.01-1000 nM for 24-72 hours. Bone resorption is quantified by measuring the area of resorption pits using microscopy or by measuring calcium release into the culture medium. Inhibition of resorption is calculated from dose-response curves. Cytotoxicity is assessed using LDH release or viability assays to ensure that observed effects are not due to cell death.
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| Animal Protocol |
Animal/Disease Models: cynomolgus monkey [2]
Doses: 12 mg/kg Route of Administration: subcutaneous injection; single dose; blood samples were drawn at 1.5, 4, 24, 48 and 72 hrs (hrs (hours)) after administration. Experimental Results: High enough to Dramatically inhibit bone resorption 1.5 to 72 hrs (hrs (hours)) after dosing. In vivo efficacy studies are conducted in ovariectomized (OVX) rodent models of postmenopausal osteoporosis or in cynomolgus monkeys. Relacatib is administered orally at doses typically ranging from 1-30 mg/kg, daily. Bone mineral density is measured by dual-energy X-ray absorptiometry (DXA) or micro-computed tomography (μCT). Bone turnover markers (e.g., NTX, CTX) are measured in serum or urine. Bone histomorphometry is performed to assess the effects on bone resorption and formation parameters. |
| ADME/Pharmacokinetics |
Pharmacokinetic studies of Relacatib in preclinical species demonstrate that the compound is orally bioavailable. PK parameters such as Cmax, Tmax, AUC, half-life, and oral bioavailability are determined in rodents and non-human primates. The compound's favorable PK properties support once-daily dosing regimens. Tissue distribution studies show accumulation in bone, the target tissue for cathepsin K inhibition. Metabolic stability and protein binding are assessed using standard in vitro assays.
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| Toxicity/Toxicokinetics |
Toxicology studies of Relacatib were conducted as part of its clinical development program. As a cathepsin K inhibitor, potential toxicities may include effects on other cathepsins, particularly cathepsin L and V, which have roles in normal tissue homeostasis. Standard toxicology studies (acute, subchronic, and chronic) were performed in rodents and non-human primates. The compound's safety profile was evaluated in clinical trials for osteoporosis. Specific toxicity findings are not widely reported in public sources.
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| References |
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| Additional Infomation |
Drug Indication
Relacatib has been studied for the treatment of osteoporosis and bone metastases. Mechanism of Action Relacatib is a small molecule drug that inhibits the activity of cathepsin K, an enzyme that appears to be associated with osteoporosis, osteoarthritis, and certain other diseases that cause bone degeneration. Relacatib (SB-462795) was a clinical-stage drug candidate for the treatment of osteoporosis and other bone resorption disorders, developed by GlaxoSmithKline. It represents an important example of a cathepsin K inhibitor that reached clinical testing. The compound's high potency and oral bioavailability made it a promising candidate, though its development status is not currently active. Relacatib is available for research purposes and serves as a reference compound for studying cathepsin K biology and bone metabolism. |
| Molecular Formula |
C27H32N4O6S
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|---|---|
| Molecular Weight |
540.63
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| Exact Mass |
540.204
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| CAS # |
362505-84-8
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| Related CAS # |
362505-84-8
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| PubChem CID |
6918602
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| Appearance |
White to off-white solid powder
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| LogP |
5.333
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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 |
8
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| Heavy Atom Count |
38
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| Complexity |
967
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| Defined Atom Stereocenter Count |
3
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| SMILES |
C[C@@H]1CC[C@@H](C(=O)CN1S(=O)(=O)C2=CC=CC=N2)NC(=O)[C@H](CC(C)C)NC(=O)C3=CC4=CC=CC=C4O3
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| InChi Key |
BWYBBMQLUKXECQ-GIVPXCGWSA-N
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| InChi Code |
InChI=1S/C27H32N4O6S/c1-17(2)14-21(30-27(34)24-15-19-8-4-5-9-23(19)37-24)26(33)29-20-12-11-18(3)31(16-22(20)32)38(35,36)25-10-6-7-13-28-25/h4-10,13,15,17-18,20-21H,11-12,14,16H2,1-3H3,(H,29,33)(H,30,34)/t18-,20+,21+/m1/s1 SMILES
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| Chemical Name |
N-((S)-4-methyl-1-(((4S,7R)-7-methyl-3-oxo-1-(pyridin-2-ylsulfonyl)azepan-4-yl)amino)-1-oxopentan-2-yl)benzofuran-2-carboxamide.
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| Synonyms |
SB462795 SB-462795 SB 462795 D 06634D-06634D06634GSK462795 GSK-462795 GSK 462795
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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: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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 : ~40 mg/mL (~73.99 mM)
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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 | 1.8497 mL | 9.2485 mL | 18.4969 mL | |
| 5 mM | 0.3699 mL | 1.8497 mL | 3.6994 mL | |
| 10 mM | 0.1850 mL | 0.9248 mL | 1.8497 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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