Odanacatib
Identification
- Generic Name
- Odanacatib
- DrugBank Accession Number
- DB06670
- Background
Odanacatib is an inhibiter of cathepsin K which was originally developed be Merck & Co as a new treatment for osteoporosis 1. The drug made it to phase III trials before abandoned due to increased stroke.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
- Weight
- Average: 525.56
Monoisotopic: 525.170925567 - Chemical Formula
- C25H27F4N3O3S
- Synonyms
- Odanacatib
- External IDs
- MK-0822
- MK0822
Pharmacology
- Indication
Investigated for use/treatment in osteoporosis 1.
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- Pharmacodynamics
Increases bone mineral density and reduces risk of fractures in osteoporosis 2.
- Mechanism of action
Odanacatib inhibits cathepsin K, likely by binding to its active site 7. Cathepsin K is a cysteine protease enzyme which is secreted by osteoclasts 5. Cathepsin K is responsible for the breakdown of collagen in the bone matrix as part of bone resorption. The inhibition of this enzyme results in decreased bone resorption without affecting bone deposition resulting in increased bone mineral density. This increased bone mineral density strengthens the bone which leads to fewer fractures in osteoporosis.
Target Actions Organism UCathepsin K inhibitorHumans - Absorption
Tmax of 2-6h 2. The absolute bioavailabilities observed with 30mg and 50 mg doses are 70% and 30% respectively. When taken with high fat meals the 50mg dose's bioavailability increases to 49% and tmax increases to 10.5h 3.
- Volume of distribution
100L 3
- Protein binding
97.5% bound to plasma proteins 4.
- Metabolism
The major metabolite is the product of hydroxylation by CYP3A4 and CYP2C8 4. This metabolite is active but is 25 times less effective at inhibiting cathepsin K than odanacatib. The other metabolites are produced through glutathione conjugation, hydrolysis, dealkylation, glucuronidation, oxidation, and cyclization.
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- Route of elimination
16.9% excreted in urine. 74.5% excreted in feces.
- Half-life
Apparent half life observed to be 87.3-94.7h 2.
- Clearance
Total clearance of 0.8L/h 3.
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Odanacatib was found to increase the risk of stroke 1. No further toxicological studies have been performed.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Odanacatib can be increased when it is combined with Abametapir. Abatacept The metabolism of Odanacatib can be increased when combined with Abatacept. Abemaciclib The serum concentration of Abemaciclib can be increased when it is combined with Odanacatib. Abiraterone The metabolism of Odanacatib can be decreased when combined with Abiraterone. Abrocitinib The serum concentration of Odanacatib can be increased when it is combined with Abrocitinib. - Food Interactions
- Not Available
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as leucine and derivatives. These are compounds containing leucine or a derivative thereof resulting from reaction of leucine at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.
- Kingdom
- Organic compounds
- Super Class
- Organic acids and derivatives
- Class
- Carboxylic acids and derivatives
- Sub Class
- Amino acids, peptides, and analogues
- Direct Parent
- Leucine and derivatives
- Alternative Parents
- Biphenyls and derivatives / Alpha amino acid amides / Benzenesulfonyl compounds / Aralkylamines / N-acyl amines / Sulfones / Secondary carboxylic acid amides / Nitriles / Dialkylamines / Organopnictogen compounds show 5 more
- Substituents
- Alkyl fluoride / Alkyl halide / Alpha-amino acid amide / Amine / Aralkylamine / Aromatic homomonocyclic compound / Benzenesulfonyl group / Benzenoid / Biphenyl / Carbonitrile show 23 more
- Molecular Framework
- Aromatic homomonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- N673F6W2VH
- CAS number
- 603139-19-1
- InChI Key
- FWIVDMJALNEADT-SFTDATJTSA-N
- 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
- IUPAC Name
- (2S)-N-(1-cyanocyclopropyl)-4-fluoro-4-methyl-2-{[(1S)-2,2,2-trifluoro-1-{4'-methanesulfonyl-[1,1'-biphenyl]-4-yl}ethyl]amino}pentanamide
- SMILES
- CC(C)(F)C[C@H](N[C@@H](C1=CC=C(C=C1)C1=CC=C(C=C1)S(C)(=O)=O)C(F)(F)F)C(=O)NC1(CC1)C#N
References
- General References
- Mullard A: Merck &Co. drops osteoporosis drug odanacatib. Nat Rev Drug Discov. 2016 Sep 29;15(10):669. doi: 10.1038/nrd.2016.207. [Article]
- 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. 2014 Feb;99(2):552-60. doi: 10.1210/jc.2013-1688. Epub 2013 Nov 25. [Article]
- 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: The Absolute Bioavailability and Effect of Food on the Pharmacokinetics of Odanacatib: A Stable-Label i.v./Oral Study in Healthy Postmenopausal Women. Drug Metab Dispos. 2016 Sep;44(9):1450-8. doi: 10.1124/dmd.116.069906. Epub 2016 Jul 11. [Article]
- Kassahun K, McIntosh I, Koeplinger K, Sun L, Talaty JE, Miller DL, Dixon R, Zajic S, Stoch SA: Disposition and metabolism of the cathepsin K inhibitor odanacatib in humans. Drug Metab Dispos. 2014 May;42(5):818-27. doi: 10.1124/dmd.113.056580. Epub 2014 Feb 19. [Article]
- Boonen S, Rosenberg E, Claessens F, Vanderschueren D, Papapoulos S: Inhibition of cathepsin K for treatment of osteoporosis. Curr Osteoporos Rep. 2012 Mar;10(1):73-9. doi: 10.1007/s11914-011-0085-9. [Article]
- Gauthier JY, Chauret N, Cromlish W, Desmarais S, Duong LT, Falgueyret JP, Kimmel DB, Lamontagne S, Leger S, LeRiche T, Li CS, Masse F, McKay DJ, Nicoll-Griffith DA, Oballa RM, Palmer JT, Percival MD, Riendeau D, Robichaud J, Rodan GA, Rodan SB, Seto C, Therien M, Truong VL, Venuti MC, Wesolowski G, Young RN, Zamboni R, Black WC: The discovery of odanacatib (MK-0822), a selective inhibitor of cathepsin K. Bioorg Med Chem Lett. 2008 Feb 1;18(3):923-8. doi: 10.1016/j.bmcl.2007.12.047. Epub 2008 Jan 15. [Article]
- Black WC: Peptidomimetic inhibitors of cathepsin K. Curr Top Med Chem. 2010;10(7):745-51. [Article]
- External Links
- PubChem Compound
- 10152654
- PubChem Substance
- 347827781
- ChemSpider
- 8328162
- BindingDB
- 50255753
- ChEMBL
- CHEMBL481611
- ZINC
- ZINC000042893657
- Wikipedia
- Odanacatib
- MSDS
- Download (25.4 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 3 Completed Treatment Osteoporosis 2 3 Terminated Treatment Osteoporosis 1 3 Terminated Treatment Postmenopausal Osteoporosis 1 3 Withdrawn Prevention Breast Cancer 1 3 Withdrawn Prevention Prostate Cancer 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.00666 mg/mL ALOGPS logP 4.04 ALOGPS logP 3.33 Chemaxon logS -4.9 ALOGPS pKa (Strongest Acidic) 11.12 Chemaxon pKa (Strongest Basic) 3.25 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 99.06 Å2 Chemaxon Rotatable Bond Count 10 Chemaxon Refractivity 126.95 m3·mol-1 Chemaxon Polarizability 50.35 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 212.369 predictedDeepCCS 1.0 (2019) [M+H]+ 214.46689 predictedDeepCCS 1.0 (2019) [M+Na]+ 220.22218 predictedDeepCCS 1.0 (2019)
Targets
![](https://go.drugbank.com/assets/locked/DrugTargets2-682eb846d210ae4bf33ca03febccfb57bb1c61318e699b729e5df4dfab2c5b67.png)
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Proteoglycan binding
- Specific Function
- Closely involved in osteoclastic bone resorption and may participate partially in the disorder of bone remodeling. Displays potent endoprotease activity against fibrinogen at acid pH. May play an i...
- Gene Name
- CTSK
- Uniprot ID
- P43235
- Uniprot Name
- Cathepsin K
- Molecular Weight
- 36965.82 Da
References
- Gauthier JY, Chauret N, Cromlish W, Desmarais S, Duong LT, Falgueyret JP, Kimmel DB, Lamontagne S, Leger S, LeRiche T, Li CS, Masse F, McKay DJ, Nicoll-Griffith DA, Oballa RM, Palmer JT, Percival MD, Riendeau D, Robichaud J, Rodan GA, Rodan SB, Seto C, Therien M, Truong VL, Venuti MC, Wesolowski G, Young RN, Zamboni R, Black WC: The discovery of odanacatib (MK-0822), a selective inhibitor of cathepsin K. Bioorg Med Chem Lett. 2008 Feb 1;18(3):923-8. doi: 10.1016/j.bmcl.2007.12.047. Epub 2008 Jan 15. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Kassahun K, McIntosh I, Koeplinger K, Sun L, Talaty JE, Miller DL, Dixon R, Zajic S, Stoch SA: Disposition and metabolism of the cathepsin K inhibitor odanacatib in humans. Drug Metab Dispos. 2014 May;42(5):818-27. doi: 10.1124/dmd.113.056580. Epub 2014 Feb 19. [Article]
- Marcantonio EE, Ballard J, Gibson CR, Kassahun K, Palamanda J, Tang C, Evers R, Liu C, Zajic S, Mahon C, Mostoller K, Hreniuk D, Mehta A, Morris D, Wagner JA, Stoch SA: Prednisone has no effect on the pharmacokinetics of CYP3A4 metabolized drugs - midazolam and odanacatib. J Clin Pharmacol. 2014 Nov;54(11):1280-9. doi: 10.1002/jcph.338. Epub 2014 Jun 25. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C8
- Uniprot ID
- P10632
- Uniprot Name
- Cytochrome P450 2C8
- Molecular Weight
- 55824.275 Da
References
- Kassahun K, McIntosh I, Koeplinger K, Sun L, Talaty JE, Miller DL, Dixon R, Zajic S, Stoch SA: Disposition and metabolism of the cathepsin K inhibitor odanacatib in humans. Drug Metab Dispos. 2014 May;42(5):818-27. doi: 10.1124/dmd.113.056580. Epub 2014 Feb 19. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- Multidrug resistance protein 1
- Molecular Weight
- 141477.255 Da
References
- Kassahun K, McIntosh I, Koeplinger K, Sun L, Talaty JE, Miller DL, Dixon R, Zajic S, Stoch SA: Disposition and metabolism of the cathepsin K inhibitor odanacatib in humans. Drug Metab Dispos. 2014 May;42(5):818-27. doi: 10.1124/dmd.113.056580. Epub 2014 Feb 19. [Article]
Drug created at March 19, 2008 16:47 / Updated at February 21, 2021 18:52