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| 1mg |
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Purity: ≥98%
Relacatib (SB462795 and GSK462795) is a novel and orally bioavailable small molecule inhibitor of cathepsin K that inhibits bone resorption both in vitro in human tissue and in vivo in cynomolgus monkeys. SB-462795 is a potent inhibitor of human cathepsins K, L, and V (K(i, app)=41, 68, and 53 pM, respectively) that exhibits 39-300-fold selectivity over other cathepsins. SB-462795 inhibited endogenous cathepsin K in situ in human osteoclasts and human osteoclast-mediated bone resorption with IC50 of approximately 45 nM and approximately 70 nM, respectively.
| 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].
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| 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].
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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. |
| References |
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| Additional Infomation |
Drug Indication
Investigated for use/treatment in 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 implicated in osteoporosis, osteoarthritis and certain other disorders causing bone degradation. |
| 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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