Details of the Drug

General Information of Drug (ID: DM1EO3G)

Drug Name
Odanacatib
Synonyms MK 0822; MK0822; MK-0822A; Odanacatib (USAN)
Indication
Disease Entry ICD 11 Status REF
Osteoporosis FB83.0 Phase 3 [1]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 1 Molecular Weight (mw) 525.6
Logarithm of the Partition Coefficient (xlogp) 4.1
Rotatable Bond Count (rotbonds) 9
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 9
ADMET Property
Absorption Tmax
The time to maximum plasma concentration (Tmax) is 1-2 days [2]
Clearance
The total body clearance of drug is 0.8 L/h [3]
Half-life
The concentration or amount of drug in body reduced by one-half in 87.3 - 94.7 hours [4]
Metabolism
The drug is metabolized via the CYP3A4 and CYP2C8 [5]
Vd
The volume of distribution (Vd) of drug is 100 L [3]
Chemical Identifiers
Formula
C25H27F4N3O3S
IUPAC Name
(2S)-N-(1-cyanocyclopropyl)-4-fluoro-4-methyl-2-[[(1S)-2,2,2-trifluoro-1-[4-(4-methylsulfonylphenyl)phenyl]ethyl]amino]pentanamide
Canonical 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
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
Cross-matching ID
PubChem CID
10152654
CAS Number
603139-19-1
DrugBank ID
DB06670
TTD ID
D0J6AU
INTEDE ID
DR1185

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Cathepsin K (CTSK) TTDZN01 CATK_HUMAN Inhibitor [6]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [7]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Substrate [7]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

ICD Disease Classification 15 Disease of the musculoskeletal system/connective tissue
Disease Class ICD-11: FA20 Rheumatoid arthritis
The Studied Tissue Bone marrow
The Studied Disease Osteoporosis [ICD-11:FA20]
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Cathepsin K (CTSK) DTT CTSK 2.85E-01 -1.14 -2.61
Cytochrome P450 2C8 (CYP2C8) DME CYP2C8 1.23E-01 4.59E-02 6.37E-01
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 8.60E-02 1.58E-01 1.36E+00
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 ClinicalTrials.gov (NCT01803607) Efficacy and Safety of Odanacatib in Postmenopausal Women Previously Treated With Oral Bisphosphonate (MK-0822-076). U.S. National Institutes of Health.
2 Yang BB, Kido A: Pharmacokinetics and pharmacodynamics of pegfilgrastim. Clin Pharmacokinet. 2011 May;50(5):295-306. doi: 10.2165/11586040-000000000-00000.
3 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.
4 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.
5 Picq M, Chen P, Perez M, Michaud M, Vericel E, Guichardant M, Lagarde M: DHA metabolism: targeting the brain and lipoxygenation. Mol Neurobiol. 2010 Aug;42(1):48-51. doi: 10.1007/s12035-010-8131-7. Epub 2010 Apr 28.
6 A novel c-Met inhibitor, MK8033, synergizes with carboplatin plus paclitaxel to inhibit ovarian cancer cell growth. Oncol Rep. 2013 May;29(5):2011-8.
7 Disposition and metabolism of the cathepsin K inhibitor odanacatib in humans. Drug Metab Dispos. 2014 May;42(5):818-27.