Odanacatib (MK0822)
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MedKoo CAT#: 202062

CAS#: 603139-19-1

Description: Odanacatib, also known as MK-0822, is an inhibitor of cathepsin K with potential anti-osteoporotic activity. Odanacatib selectively binds to and inhibits the activity of cathepsin K, which may result in a reduction in bone resorption, improvement of bone mineral density, and a reversal in osteoporotic changes. Cathepsin K, a tissue-specific cysteine protease that catalyzes degradation of bone matrix proteins such as collagen I/II, elastin, and osteonectin plays an important role in osteoclast function and bone resorption. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).


Chemical Structure

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Odanacatib (MK0822)
CAS# 603139-19-1

Theoretical Analysis

MedKoo Cat#: 202062
Name: Odanacatib (MK0822)
CAS#: 603139-19-1
Chemical Formula: C25H27F4N3O3S
Exact Mass: 525.17093
Molecular Weight: 525.56
Elemental Analysis: C, 57.13; H, 5.18; F, 14.46; N, 8.00; O, 9.13; S, 6.10

Price and Availability

Size Price Availability Quantity
10.0mg USD 90.0 Ready to ship
25.0mg USD 150.0 Ready to ship
50.0mg USD 250.0 Ready to ship
100.0mg USD 450.0 Ready to ship
200.0mg USD 850.0 Ready to ship
500.0mg USD 1650.0 Ready to ship
1.0g USD 2950.0 2 Weeks
2.0g USD 4250.0 2 Weeks
5.0g USD 6950.0 2 Weeks
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Synonym: MK0822; MK-0822; MK 0822; Odanacatib .

IUPAC/Chemical Name: (S)-N-(1-cyanocyclopropyl)-4-fluoro-4-methyl-2-(((S)-2,2,2-trifluoro-1-(4'-(methylsulfonyl)-[1,1'-biphenyl]-4-yl)ethyl)amino)pentanamide

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

SMILES Code: CC(C)(F)C[C@H](N[C@@H](C1=CC=C(C2=CC=C(S(=O)(C)=O)C=C2)C=C1)C(F)(F)F)C(NC3(C#N)CC3)=O

Appearance: white solid powder, m.p. = 223 - 224 oC

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Biological target: Odanacatib (MK-0822) is a potent and selective inhibitor of cathepsin K, with an IC50 of 0.2 nM for human cathepsin K.
In vitro activity: Human breast cancer cell lines MDA-MB-231 were treated with different concentrations of ODN and performed invasion, adhesion and migration assays and, RT-PCR and western blot to evaluate the effect of ODN on the metastatic potential of breast cancer cells. ODN markedly decreased wound healing cell migration, invasion and adhesion at a dose dependent manner. ODN inhibits cell invasion by decreasing the matrix metalloproteinase (MMP-9) with the upregulation of TIMP-1 expression. ODN effectively inhibited the phosphorylation of extracellular signal-regulated kinase (ERK), p38, and c-Jun N-terminal Kinase (JNK), and blocked the expression of β-integrins and FAK proteins. ODN also significantly inhibited PI3K downstream targets Rac1, Cdc42, paxillin and Src which are critical for cell adhesion, migration and cytoskeletal reorganization. ODN exerts anti-metastatic action through inhibition of signaling pathway for MMP-9, PI3K and MAPK. This indicates potential therapeutic effects of ODN in the treatment of metastatic breast cancer. Reference: Mol Biol Rep. 2021 Jan;48(1):105-116. https://doi.org/10.1007/s11033-020-05951-0
In vivo activity: Two related studies in OVX monkeys that evaluated the effects of ODN on bone turnover, BMD, and bone strength had findings that were common with conventional antiresorptives and other findings that were different. OVX monkeys were treated for 21 months with either vehicle, ODN 6 mg/kg, or ODN 30 mg/kg (orally, once daily), and compared with intact animals. ODN treatment persistently suppressed bone resorption markers (urinary NTX by 75% to 90% and serum CTX by 40% to 55%) and serum bone formation markers (BSAP by 30% to 35% and P1NP by 60% to 70%) versus vehicle-treated OVX monkeys. In the lumbar vertebrae and iliac crest, both doses of ODN prevented bone loss and maintained bone mass at a level comparable to intact animals. BFRs in trabecular bone at the iliac crest and lumbar vertebrae decreased by comparable amounts. However, in the femoral neck and proximal femur, there was no effect on endocortical BFR, while trabecular and intracortical BFR were reduced. Furthermore, ODN stimulated long-term femoral neck and proximal femur periosteal BFR by 3.5-fold and 6-fold, respectively, with the 30 mg/kg dose versus vehicle, resulting in a 21% and 19% increase in cortical thickness in the femoral neck and proximal femur, respectively. Thus, unlike conventional antiresorptives, ODN displayed compartment-specific effects on trabecular versus cortical bone formation, with treatment resulting in marked increases in periosteal bone formation and cortical thickness in OVX monkeys, whereas trabecular bone formation was reduced. This compartment-specific effect of ODN in OVX monkeys is similar to that previously reported for balicatib and relacatib. Another point of difference from current antiresorptives is the maintenance of osteoclast numbers in the ODN-treated groups compared with the vehicle controls. If the osteoclasts remain viable, they could still be functional, even though they could no longer resorb bone. Serum level of TRAP5b, an indicator of osteoclast cell number and biomarker of osteoclast viability was maintained, providing support for the distinct mechanism of cathepsin K inhibition in effectively suppressing bone resorption without reducing osteoclast numbers. Reference: Clin Interv Aging. 2012;7:235-47. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22866001/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 15.0 28.5

Preparing Stock Solutions

The following data is based on the product molecular weight 525.56 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Leung P, Pickarski M, Zhuo Y, Masarachia PJ, Duong LT. The effects of the cathepsin K inhibitor odanacatib on osteoclastic bone resorption and vesicular trafficking. Bone. 2011 Oct;49(4):623-35. doi: 10.1016/j.bone.2011.06.014. Epub 2011 Jun 22. PMID: 21718816. 2. Vashum Y, Premsingh R, Kottaiswamy A, Soma M, Padmanaban A, Kalaiselvan P, Samuel S. Inhibitory effect of cathepsin K inhibitor (ODN-MK-0822) on invasion, migration and adhesion of human breast cancer cells in vitro. Mol Biol Rep. 2021 Jan;48(1):105-116. doi: 10.1007/s11033-020-05951-0. Epub 2020 Dec 8. PMID: 33294960. 3. Ng KW. Potential role of odanacatib in the treatment of osteoporosis. Clin Interv Aging. 2012;7:235-47. doi: 10.2147/CIA.S26729. Epub 2012 Jul 12. PMID: 22866001; PMCID: PMC3410681.
In vitro protocol: 1. Leung P, Pickarski M, Zhuo Y, Masarachia PJ, Duong LT. The effects of the cathepsin K inhibitor odanacatib on osteoclastic bone resorption and vesicular trafficking. Bone. 2011 Oct;49(4):623-35. doi: 10.1016/j.bone.2011.06.014. Epub 2011 Jun 22. PMID: 21718816. 2. Vashum Y, Premsingh R, Kottaiswamy A, Soma M, Padmanaban A, Kalaiselvan P, Samuel S. Inhibitory effect of cathepsin K inhibitor (ODN-MK-0822) on invasion, migration and adhesion of human breast cancer cells in vitro. Mol Biol Rep. 2021 Jan;48(1):105-116. doi: 10.1007/s11033-020-05951-0. Epub 2020 Dec 8. PMID: 33294960.
In vivo protocol: 1. Ng KW. Potential role of odanacatib in the treatment of osteoporosis. Clin Interv Aging. 2012;7:235-47. doi: 10.2147/CIA.S26729. Epub 2012 Jul 12. PMID: 22866001; PMCID: PMC3410681.

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1: Chapurlat RD. Treatment of postmenopausal osteoporosis with odanacatib. Expert Opin Pharmacother. 2014 Jan 24. [Epub ahead of print] PubMed PMID: 24456412.

2: Odanacatib, a cathepsin K inhibitor, superior to alendronate. Bonekey Rep. 2013 Sep 4;2:426. doi: 10.1038/bonekey.2013.160. eCollection 2013. PubMed PMID: 24422127; PubMed Central PMCID: PMC3789222.

3: Retraction notice: Odanacatib for the treatment of postmenopausal osteoporosis. Expert Opin Pharmacother. 2014 Jan;15(1):151. doi: 10.1517/14656566.2014.868399. Epub 2013 Nov 30. PubMed PMID: 24289716.

4: Anderson MS, Gendrano IN, Liu C, Jeffers S, Mahon C, Mehta A, Mostoller K, Zajic S, Morris D, Lee J, Stoch SA. Odanacatib, a selective cathepsin K inhibitor, demonstrates comparable pharmacodynamics and pharmacokinetics in older men and postmenopausal women. J Clin Endocrinol Metab. 2013 Dec 20:jc20131688. [Epub ahead of print] PubMed PMID: 24276460.

5: Chapurlat RD. Odanacatib for the treatment of postmenopausal osteoporosis. Expert Opin Pharmacother. 2014 Jan;15(1):97-102. doi: 10.1517/14656566.2014.853038. Epub 2013 Oct 25. Retraction in: Expert Opin Pharmacother. 2014 Jan;15(1):151. PubMed PMID: 24156249.

6: Stoch SA, Witter R, Hrenuik D, Liu C, Zajic S, Mehta A, Chandler P, Morris D, Xue H, Denker A, Wagner JA. Odanacatib does not influence the single dose pharmacokinetics and pharmacodynamics of warfarin. J Popul Ther Clin Pharmacol. 2013;20(3):e312-20. Epub 2013 Oct 2. PubMed PMID: 24142206.

7: Jensen PR, Andersen TL, Pennypacker BL, Duong le T, Delaissé JM. The bone resorption inhibitors odanacatib and alendronate affect post-osteoclastic events differently in ovariectomized rabbits. Calcif Tissue Int. 2014 Feb;94(2):212-22. doi: 10.1007/s00223-013-9800-0. Epub 2013 Oct 2. PubMed PMID: 24085265.

8: Bonnick S, De Villiers T, Odio A, Palacios S, Chapurlat R, Dasilva C, Scott BB, Le Bailly De Tilleghem C, Leung AT, Gurner D. Effects of Odanacatib on BMD and Safety in the Treatment of Osteoporosis in Postmenopausal Women Previously Treated With Alendronate: A Randomized Placebo-Controlled Trial. J Clin Endocrinol Metab. 2013 Dec;98(12):4727-35. doi: 10.1210/jc.2013-2020. Epub 2013 Sep 24. PubMed PMID: 24064689.

9: Zerbini CA, McClung MR. Odanacatib in postmenopausal women with low bone mineral density: a review of current clinical evidence. Ther Adv Musculoskelet Dis. 2013 Aug;5(4):199-209. doi: 10.1177/1759720X13490860. PubMed PMID: 23904864; PubMed Central PMCID: PMC3728981.

10: Williams DS, McCracken PJ, Purcell M, Pickarski M, Mathers PD, Savitz AT, Szumiloski J, Jayakar RY, Somayajula S, Krause S, Brown K, Winkelmann CT, Scott BB, Cook L, Motzel SL, Hargreaves R, Evelhoch JL, Cabal A, Dardzinski BJ, Hangartner TN, Duong le T. Effect of odanacatib on bone turnover markers, bone density and geometry of the spine and hip of ovariectomized monkeys: a head-to-head comparison with alendronate. Bone. 2013 Oct;56(2):489-96. doi: 10.1016/j.bone.2013.06.008. Epub 2013 Jun 24. PubMed PMID: 23806798.

11: Cabal A, Jayakar RY, Sardesai S, Phillips EA, Szumiloski J, Posavec DJ, Mathers PD, Savitz AT, Scott BB, Winkelmann CT, Motzel S, Cook L, Hargreaves R, Evelhoch JL, Dardzinski BJ, Hangartner TN, McCracken PJ, Duong le T, Williams DS. High-resolution peripheral quantitative computed tomography and finite element analysis of bone strength at the distal radius in ovariectomized adult rhesus monkey demonstrate efficacy of odanacatib and differentiation from alendronate. Bone. 2013 Oct;56(2):497-505. doi: 10.1016/j.bone.2013.06.011. Epub 2013 Jun 20. PubMed PMID: 23791777.

12: Stoch SA, Witter R, Hreniuk D, Liu C, Zajic S, Mehta A, Brandquist C, Dempsey C, Degroot B, Stypinski D, Denker A, Wagner JA. Absence of clinically relevant drug-drug interaction between odanacatib and digoxin after concomitant administration. Int J Clin Pharmacol Ther. 2013 Aug;51(8):688-92. doi: 10.5414/CP201864. PubMed PMID: 23782582.

13: Nakamura T, Shiraki M, Fukunaga M, Tomomitsu T, Santora AC, Tsai R, Fujimoto G, Nakagomi M, Tsubouchi H, Rosenberg E, Uchida S. Effect of the cathepsin K inhibitor odanacatib administered once weekly on bone mineral density in Japanese patients with osteoporosis-a double-blind, randomized, dose-finding study. Osteoporos Int. 2014 Jan;25(1):367-76. doi: 10.1007/s00198-013-2398-2. Epub 2013 May 29. PubMed PMID: 23716037.

14: Brixen K, Chapurlat R, Cheung AM, Keaveny TM, Fuerst T, Engelke K, Recker R, Dardzinski B, Verbruggen N, Ather S, Rosenberg E, de Papp AE. Bone density, turnover, and estimated strength in postmenopausal women treated with odanacatib: a randomized trial. J Clin Endocrinol Metab. 2013 Feb;98(2):571-80. doi: 10.1210/jc.2012-2972. Epub 2013 Jan 21. PubMed PMID: 23337728.

15: Fratzl-Zelman N, Roschger P, Fisher JE, Duong le T, Klaushofer K. Effects of Odanacatib on bone mineralization density distribution in thoracic spine and femora of ovariectomized adult rhesus monkeys: a quantitative backscattered electron imaging study. Calcif Tissue Int. 2013 Mar;92(3):261-9. doi: 10.1007/s00223-012-9673-7. Epub 2012 Nov 23. PubMed PMID: 23179105.

16: Stoch SA, Zajic S, Stone JA, Miller DL, van Bortel L, Lasseter KC, Pramanik B, Cilissen C, Liu Q, Liu L, Scott BB, Panebianco D, Ding Y, Gottesdiener K, Wagner JA. Odanacatib, a selective cathepsin K inhibitor to treat osteoporosis: safety, tolerability, pharmacokinetics and pharmacodynamics--results from single oral dose studies in healthy volunteers. Br J Clin Pharmacol. 2013 May;75(5):1240-54. doi: 10.1111/j.1365-2125.2012.04471.x. PubMed PMID: 23013236; PubMed Central PMCID: PMC3635595.

17: Ng KW. Potential role of odanacatib in the treatment of osteoporosis. Clin Interv Aging. 2012;7:235-47. doi: 10.2147/CIA.S26729. Epub 2012 Jul 12. Review. PubMed PMID: 22866001; PubMed Central PMCID: PMC3410681.

18: Langdahl B, Binkley N, Bone H, Gilchrist N, Resch H, Rodriguez Portales J, Denker A, Lombardi A, Le Bailly De Tilleghem C, Dasilva C, Rosenberg E, Leung A. Odanacatib in the treatment of postmenopausal women with low bone mineral density: five years of continued therapy in a phase 2 study. J Bone Miner Res. 2012 Nov;27(11):2251-8. doi: 10.1002/jbmr.1695. PubMed PMID: 22777865.

19: Jayakar RY, Cabal A, Szumiloski J, Sardesai S, Phillips EA, Laib A, Scott BB, Pickarski M, Duong le T, Winkelmann CT, McCracken PJ, Hargreaves R, Hangartner TN, Williams DS. Evaluation of high-resolution peripheral quantitative computed tomography, finite element analysis and biomechanical testing in a pre-clinical model of osteoporosis: a study with odanacatib treatment in the ovariectomized adult rhesus monkey. Bone. 2012 Jun;50(6):1379-88. doi: 10.1016/j.bone.2012.03.017. Epub 2012 Mar 24. PubMed PMID: 22469953.

20: Khosla S. Odanacatib: location and timing are everything. J Bone Miner Res. 2012 Mar;27(3):506-8. doi: 10.1002/jbmr.1541. PubMed PMID: 22354850.



Additional Information

Odanacatib (pINN; codenamed MK-0822) is an investigational treatment for osteoporosis and bone metastasis. It is an inhibitor of cathepsin K,  an enzyme involved in bone resorption. It is being developed by Merck & Co. As of November 2009, Merck is conducting phase III clinical trials.