Odanacatib

• CAT Number: I004270
• CAS Number: 603139-19-1
• Molecular Formula: C25H27F4N3O3S
• Molecular Weight: 525.6
• Purity: ≥95%
• Target: Cathepsin
• Solubility: DMSO ≥102mg/mL Water <1.2mg/mL Ethanol ≥2.9mg/mL
• Storage: 3 years -20C powder
• IC50: 0.2 nM/1 nM(human/rabbi cathepsin K)
• InChI: 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
• InChIKey: FWIVDMJALNEADT-SFTDATJTSA-N
• SMILES: CS(C(C=C1)=CC=C1C2=CC=C([C@@H](C(F)(F)F)N([H])[C@H](C(N([H])C3(CC3)C#N)=O)CC(F)(C)C)C=C2)(=O)=O

Odanacatib (MK 0822) is a potent, selective, and neutral inhibitor of cathepsin K (human/rabbit) with IC50 of 0.2 nM/1 nM, and demonstrated high selectivity versus off-target cathepsin B, L, S.IC50 value: 0.2 nM/1 nM(human/rabbi cathepsin K)in vitro: In vitro, Odanacatib shows the high inhibitory activity and selectivity on cathepsin K with IC50 values of 0.2 nM and 1 nM for human cathepsin K and rabbit cathepsin K, respectively. Furthermore, Odanacatib also shows similar potencies in whole human cell enzyme occupancy assays with corrected IC50 of 5 nM. A recent study shows that Odanacatib results in reduction of Osteoclast (OC) resorption activity by interrupting intracellular vesicular trafficking.in vivo: n preclinical rats, Odanacatib (10 mg/kg) exhibits excellent pharmacokinetics with clearance (Cl: 2 mL kg-1 min-1), low volume of distribution (Vdss: 1.1 L kg-1), half-life (T1/2: 6 hours) and oral bioavailability (F: 8%), respectively. Besides, Odanacatib also exhibits excellent metabolic stability in rat hepatocytes with a 96% recovery of the parent identity. Odanacatib (ODN) administrated by p.o. prevents bone loss in ovariectomized (OVX) rabbits in a dose-related manner. Moreover, Odanacatib (9μM/day) leads to a significant increase in proximal femur bone mineral density (BMD) (7.8%), femoral neck BMD (10.8%) and the greater trochanter BMD (6.5%).

Reference

1:Long-term treatment with odanacatib maintains normal trabecular biomechanical properties in ovariectomized adult monkeys as demonstrated by micro-CT-based finite element analysis. Cabal A, Williams DS, Jayakar RY, Zhang J, Sardesai S, Duong LT.Bone Rep. 2017 Jan 7;6:26-33. doi: 10.1016/j.bonr.2017.01.001. eCollection 2017 Jun. PMID: 28377978 Free PMC Article2:Role of odanacatib in reducing bone loss due to endodontic disease: An overview. Bahuguna R, Jain A, Khan SA, Arvind MS.J Int Soc Prev Community Dent. 2016 Dec;6(Suppl 3):S175-S181. doi: 10.4103/2231-0762.197183. Review. PMID: 28217533 Free PMC Article3:Identification of mouse cathepsin K structural elements that regulate the potency of odanacatib. Law S, Andrault PM, Aguda AH, Nguyen NT, Kruglyak N, Brayer GD, Brömme D.Biochem J. 2017 Feb 20;474(5):851-864. doi: 10.1042/BCJ20160985. PMID: 28049758 4:Odanacatib, effects of 16-month treatment and discontinuation of therapy on bone mass, turnover and strength in the ovariectomized rabbit model of osteopenia. Duong LT, Crawford R, Scott K, Winkelmann CT, Wu G, Szczerba P, Gentile MA.Bone. 2016 Dec;93:86-96. doi: 10.1016/j.bone.2016.09.012. Epub 2016 Sep 15. PMID: 27639811 5:Merck &Co. drops osteoporosis drug odanacatib. Mullard A.Nat Rev Drug Discov. 2016 Sep 29;15(10):669. doi: 10.1038/nrd.2016.207. No abstract available. PMID: 27681784 6:The Absolute Bioavailability and Effect of Food on the Pharmacokinetics of Odanacatib: A Stable-Label i.v./Oral Study in Healthy Postmenopausal Women. Zajic S, Rossenu S, Hreniuk D, Kesisoglou F, McCrea J, Liu F, Sun L, Witter R, Gauthier D, Helmy R, Joss D, Ni T, Stoltz R, Stone J, Stoch SA.Drug Metab Dispos. 2016 Sep;44(9):1450-8. doi: 10.1124/dmd.116.069906. Epub 2016 Jul 11. PMID: 27402726 7:Odanacatib, a Cathepsin K Cysteine Protease Inhibitor, Kills Hookworm In Vivo. Vermeire JJ, Suzuki BM, Caffrey CR.Pharmaceuticals (Basel). 2016 Jul 4;9(3). pii: E39. doi: 10.3390/ph9030039. PMID: 27384569 Free PMC Article8:Coadministration of Rifampin Significantly Reduces Odanacatib Concentrations in Healthy Subjects. Stoch SA, Ballard J, Gibson C, Kesisoglou F, Witter R, Kassahun K, Zajic S, Mehta A, Brandquist C, Dempsey C, Stypinski D, Reitman ML.J Clin Pharmacol. 2017 Jan;57(1):110-117. doi: 10.1002/jcph.780. Epub 2016 Aug 1. PMID: 27321774 9:Effects of long term treatment with high doses of odanacatib on bone mass, bone strength, and remodeling/modeling in newly ovariectomized monkeys. Duong LT, Pickarski M, Cusick T, Chen CM, Zhuo Y, Scott K, Samadfam R, Smith SY, Pennypacker BL.Bone. 2016 Jul;88:113-24. doi: 10.1016/j.bone.2016.04.024. Epub 2016 Apr 25. PMID: 27126999 10:Continuous treatment with odanacatib for up to 8 years in postmenopausal women with low bone mineral density: a phase 2 study. Rizzoli R, Benhamou CL, Halse J, Miller PD, Reid IR, Rodríguez Portales JA, DaSilva C, Kroon R, Verbruggen N, Leung AT, Gurner D.Osteoporos Int. 2016 Jun;27(6):2099-107. doi: 10.1007/s00198-016-3503-0. Epub 2016 Feb 15. PMID: 26879200