Size | Price | Stock | Qty |
---|---|---|---|
2mg |
|
||
5mg |
|
||
10mg |
|
||
25mg |
|
||
50mg |
|
||
100mg |
|
||
250mg |
|
||
Other Sizes |
|
Purity: ≥98%
Odanacatib (also known as MK-0822) is a potent, neutral, and selective inhibitor of human/rabbit cathepsin K that may be applied to the management of bone metastases and osteoporosis. With IC50s of 0.2 nM/1 nM, it inhibits cathepsin K (human/rabbit) and shows good selectivity against off-target cathepsins B, L, and S. Odanacatib binds to cathepsin K specifically and inhibits its activity. This may reduce bone resorption, improve bone mineral density, and reverse osteoporotic changes. Approximately 16,000 postmenopausal osteoporosis patients are participating in a phase III trial to assess the potential of odanacatib to reduce fracture risk.
Targets |
Cathepsin K(human) (IC50 = 0.2 nM); Cathepsin K(human) (IC50 = 1 nM)
|
---|---|
ln Vitro |
Odanacatib exhibits strong cathepsin K inhibitory activity and selectivity in vitro, with IC50 values for human and rabbit cathepsin K of 0.2 nM and 1 nM, respectively. Additionally, with a corrected IC50 of 5 nM, odanacatib demonstrates comparable potencies in whole human cell enzyme occupancy assays.[1] Odanacatib reduces osteoclast (OC) resorption activity by blocking intracellular vesicular trafficking, according to a recent study.[2]
|
ln Vivo |
Odanacatib (10 mg/kg) in preclinical rats shows good pharmacokinetics with low volume of distribution (Vdss: 1.1 L kg-1), half-life (T1/2: 6 hours), oral bioavailability (F: 8%), and clearance (Cl: 2 mL kg-1 min-1). Furthermore, in rat hepatocytes, odanacatib shows outstanding metabolic stability with a 96% recovery of the parent identity.[1] In ovariectomized (OVX) rabbits, odanacatib (ODN) administered orally reduces bone loss in a dose-dependent manner. Additionally, Odanacatib (9 µM/day) significantly raises the bone mineral density (BMD) of the femoral neck (10.8%), the greater trochanter (6.5%), and the proximal femur (7.8%).[3] Long-term administration of Odanacatib preserves the normal biomechanical characteristics of the spine in OVX nonhuman primates while effectively inhibiting bone turnover in estrogen-deficient, skeletally mature rhesus monkeys without lowering osteoclast frequency.[4]
|
Enzyme Assay |
Odanacatib, also known as MK-0822, has been shown to exhibit high selectivity against off-target cathepsin B, L, and S. It is a potent, selective, and neutral inhibitor of cathepsin K (human/rabbit) with an IC50 of 0.2 nM/1 nM. Odanacatib binds to cathepsin K specifically and inhibits its activity. This may reduce bone resorption, improve bone mineral density, and reverse osteoporotic changes.
|
Cell Assay |
In order to evaluate cell survival, 100 nM Odanacatib (ODN) or 7 ×104 differentiated osteoclast (OC) cells/cm2 are reseeded on slices of bovine bone. On days 2, 4, 6, and 12, bone slices are fixed without any media alterations. Samples are stained for both the OC number and TRAP activity.
|
Animal Protocol |
Sixteen eight-month-old female Sprague-Dawley (SD) rats, weighing 385 ± 55 g, are provided with water and soft diet food on an as-needed basis in a temperature-controlled environment featuring regular 12-hour light and dark cycles. Four groups of four rats each are created by randomization: the sham group, the OVX + Veh group, the OVX + ODN-l group, and the OVX + ODN-h group. After implant insertion, OVX + ODN-l and OVX + ODN-h groups receive gavage once daily for eight weeks at concentrations of 1 mL/kg and 6 mL/kg, respectively, of odanacatib (ODN, 5 mg/mL). During the same period, a gavage containing 0.5% sodium carboxymethyl cellulose at a concentration of 6 mL/kg is administered to the OVX + Veh group. Following the administration of gavage, intravenous sodium pentobarbital injections are used to kill the rats in each group. Along with the surrounding bone, the implants are removed and preserved in 10% buffered formalin.
|
References |
Molecular Formula |
C25H27F4N3O3S
|
---|---|
Molecular Weight |
525.56
|
Exact Mass |
525.17
|
Elemental Analysis |
C, 57.13; H, 5.18; F, 14.46; N, 8.00; O, 9.13; S, 6.10
|
CAS # |
603139-19-1
|
Appearance |
white solid powder, m.p. = 223 - 224 oC
|
SMILES |
CC(C)(C[C@@H](C(=O)NC1(CC1)C#N)N[C@@H](C2=CC=C(C=C2)C3=CC=C(C=C3)S(=O)(=O)C)C(F)(F)F)F
|
InChi Key |
FWIVDMJALNEADT-SFTDATJTSA-N
|
InChi Code |
InChI=1S/C25H27F4N3O3S/c1-23(2,26)14-20(22(33)32-24(15-30)12-13-24)31-21(25(27,28)29)18-6-4-16(5-7-18)17-8-10-19(11-9-17)36(3,34)35/h4-11,20-21,31H,12-14H2,1-3H3,(H,32,33)/t20-,21-/m0/s1
|
Chemical Name |
(2S)-N-(1-cyanocyclopropyl)-4-fluoro-4-methyl-2-[[(1S)-2,2,2-trifluoro-1-[4-(4-methylsulfonylphenyl)phenyl]ethyl]amino]pentanamide
|
Synonyms |
Odanacatib; MK 0822; MK0822; MK-0822
|
HS Tariff Code |
2934.99.9001
|
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)
|
Solubility (In Vitro) |
|
|||
---|---|---|---|---|
Solubility (In Vivo) |
|
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 1.9027 mL | 9.5137 mL | 19.0273 mL | |
5 mM | 0.3805 mL | 1.9027 mL | 3.8055 mL | |
10 mM | 0.1903 mL | 0.9514 mL | 1.9027 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.
NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
NCT00769418 | Completed | Drug: odanacatib Drug: Comparator: Placebo |
Osteoporosis | Merck Sharp & Dohme LLC | September 2004 | Phase 1 |
NCT01068262 | Completed | Drug: Odanacatib Drug: Comparator: Placebo |
Osteoporosis | Merck Sharp & Dohme LLC | December 8, 2009 | Phase 1 |
NCT01512693 | Completed | Drug: MK-0822 | Hepatic Insufficiency | Merck Sharp & Dohme LLC | February 23, 2012 | Phase 1 |
NCT01512667 | Completed | Drug: MK-0822 | Renal Insufficiency | Merck Sharp & Dohme LLC | January 17, 2012 | Phase 1 |
NCT00729183 | Completed | Drug: Odanacatib Osteoporosis |
Osteoporosis | Merck Sharp & Dohme LLC | October 2, 2008 | Phase 3 |