Identification

Name
Odanacatib
Accession Number
DB06670
Type
Small Molecule
Groups
Investigational
Description

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.

Structure
Thumb
Synonyms
Not Available
External IDs
MK-0822 / MK0822
Categories
UNII
N673F6W2VH
CAS number
603139-19-1
Weight
Average: 525.56
Monoisotopic: 525.170925567
Chemical Formula
C25H27F4N3O3S
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[[email protected]](N[[email protected]@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

Pharmacology

Indication

Investigated for use/treatment in osteoporosis [1].

Structured Indications
Not Available
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.

TargetActionsOrganism
UCathepsin K
inhibitor
Human
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.

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].

Toxicity

Odanacatib was found to increase the risk of stroke [1]. No further toxicological studies have been performed.

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AbirateroneThe serum concentration of Odanacatib can be increased when it is combined with Abiraterone.Approved
AcetaminophenThe serum concentration of Odanacatib can be increased when it is combined with Acetaminophen.Approved
AfatinibThe serum concentration of Odanacatib can be increased when it is combined with Afatinib.Approved
AlbendazoleThe serum concentration of Odanacatib can be increased when it is combined with Albendazole.Approved, Vet Approved
AldosteroneThe serum concentration of Odanacatib can be decreased when it is combined with Aldosterone.Experimental
AlectinibThe serum concentration of Odanacatib can be increased when it is combined with Alectinib.Approved
AlfentanilThe serum concentration of Odanacatib can be increased when it is combined with Alfentanil.Approved, Illicit
AmantadineThe serum concentration of Odanacatib can be increased when it is combined with Amantadine.Approved
Aminohippuric acidThe serum concentration of Odanacatib can be increased when it is combined with Aminohippuric acid.Approved
AmiodaroneThe metabolism of Odanacatib can be decreased when combined with Amiodarone.Approved, Investigational
AmitriptylineThe serum concentration of Odanacatib can be increased when it is combined with Amitriptyline.Approved
AmlodipineThe serum concentration of Odanacatib can be increased when it is combined with Amlodipine.Approved
AmprenavirThe serum concentration of Odanacatib can be decreased when it is combined with Amprenavir.Approved
AmsacrineThe serum concentration of Odanacatib can be increased when it is combined with Amsacrine.Approved
AprepitantThe serum concentration of Odanacatib can be increased when it is combined with Aprepitant.Approved, Investigational
AstemizoleThe serum concentration of Odanacatib can be increased when it is combined with Astemizole.Approved, Withdrawn
AtazanavirThe metabolism of Odanacatib can be decreased when combined with Atazanavir.Approved, Investigational
AtenololThe serum concentration of Odanacatib can be increased when it is combined with Atenolol.Approved
AtomoxetineThe metabolism of Odanacatib can be decreased when combined with Atomoxetine.Approved
AtorvastatinThe serum concentration of Odanacatib can be increased when it is combined with Atorvastatin.Approved
AzelastineThe serum concentration of Odanacatib can be increased when it is combined with Azelastine.Approved
AzithromycinThe serum concentration of Odanacatib can be increased when it is combined with Azithromycin.Approved
BenzocaineThe serum concentration of Odanacatib can be increased when it is combined with Benzocaine.Approved
BepridilThe serum concentration of Odanacatib can be increased when it is combined with Bepridil.Approved, Withdrawn
BiperidenThe serum concentration of Odanacatib can be increased when it is combined with Biperiden.Approved
BoceprevirThe metabolism of Odanacatib can be decreased when combined with Boceprevir.Withdrawn
BortezomibThe metabolism of Odanacatib can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Odanacatib can be decreased when it is combined with Bosentan.Approved, Investigational
BosutinibThe serum concentration of Odanacatib can be increased when it is combined with Bosutinib.Approved
BromocriptineThe serum concentration of Odanacatib can be increased when it is combined with Bromocriptine.Approved, Investigational
BuprenorphineThe serum concentration of Odanacatib can be increased when it is combined with Buprenorphine.Approved, Illicit, Investigational, Vet Approved
BuspironeThe serum concentration of Odanacatib can be increased when it is combined with Buspirone.Approved, Investigational
CabazitaxelThe serum concentration of Odanacatib can be increased when it is combined with Cabazitaxel.Approved
CaffeineThe serum concentration of Odanacatib can be increased when it is combined with Caffeine.Approved
CanagliflozinThe serum concentration of Odanacatib can be increased when it is combined with Canagliflozin.Approved
CandesartanThe serum concentration of Odanacatib can be increased when it is combined with Candesartan.Approved
CaptoprilThe serum concentration of Odanacatib can be increased when it is combined with Captopril.Approved
CarbamazepineThe metabolism of Odanacatib can be increased when combined with Carbamazepine.Approved, Investigational
CarvedilolThe serum concentration of Odanacatib can be increased when it is combined with Carvedilol.Approved, Investigational
CaspofunginThe serum concentration of Odanacatib can be increased when it is combined with Caspofungin.Approved
CelecoxibThe metabolism of Odanacatib can be decreased when combined with Celecoxib.Approved, Investigational
CeritinibThe serum concentration of Odanacatib can be increased when it is combined with Ceritinib.Approved
ChloroquineThe serum concentration of Odanacatib can be increased when it is combined with Chloroquine.Approved, Vet Approved
ChlorpromazineThe serum concentration of Odanacatib can be increased when it is combined with Chlorpromazine.Approved, Vet Approved
ChlorpropamideThe serum concentration of Odanacatib can be increased when it is combined with Chlorpropamide.Approved
ChlorprothixeneThe serum concentration of Odanacatib can be increased when it is combined with Chlorprothixene.Approved, Withdrawn
CholesterolThe serum concentration of Odanacatib can be increased when it is combined with Cholesterol.Experimental
Cholic AcidThe serum concentration of Odanacatib can be decreased when it is combined with Cholic Acid.Approved
CilazaprilThe serum concentration of Odanacatib can be increased when it is combined with Cilazapril.Approved
CimetidineThe serum concentration of Odanacatib can be decreased when it is combined with Cimetidine.Approved
CiprofloxacinThe serum concentration of Odanacatib can be increased when it is combined with Ciprofloxacin.Approved, Investigational
CitalopramThe serum concentration of Odanacatib can be increased when it is combined with Citalopram.Approved
ClarithromycinThe metabolism of Odanacatib can be decreased when combined with Clarithromycin.Approved
ClemastineThe metabolism of Odanacatib can be decreased when combined with Clemastine.Approved
ClofazimineThe serum concentration of Odanacatib can be increased when it is combined with Clofazimine.Approved, Investigational
ClomipramineThe serum concentration of Odanacatib can be increased when it is combined with Clomipramine.Approved, Vet Approved
ClotrimazoleThe metabolism of Odanacatib can be decreased when combined with Clotrimazole.Approved, Vet Approved
CobicistatThe metabolism of Odanacatib can be decreased when combined with Cobicistat.Approved
ColchicineThe serum concentration of Odanacatib can be increased when it is combined with Colchicine.Approved
ColforsinThe serum concentration of Odanacatib can be increased when it is combined with Colforsin.Experimental
ConivaptanThe serum concentration of Odanacatib can be increased when it is combined with Conivaptan.Approved, Investigational
CrisaboroleThe metabolism of Odanacatib can be decreased when combined with Crisaborole.Approved
CrizotinibThe metabolism of Odanacatib can be decreased when combined with Crizotinib.Approved
CyclophosphamideThe serum concentration of Odanacatib can be increased when it is combined with Cyclophosphamide.Approved, Investigational
CyclosporineThe metabolism of Odanacatib can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
DabrafenibThe serum concentration of Odanacatib can be decreased when it is combined with Dabrafenib.Approved
DaclatasvirThe serum concentration of Odanacatib can be increased when it is combined with Daclatasvir.Approved
DactinomycinThe serum concentration of Odanacatib can be increased when it is combined with Dactinomycin.Approved
DarunavirThe metabolism of Odanacatib can be decreased when combined with Darunavir.Approved
DaunorubicinThe serum concentration of Odanacatib can be decreased when it is combined with Daunorubicin.Approved
DeferasiroxThe serum concentration of Odanacatib can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe metabolism of Odanacatib can be decreased when combined with Delavirdine.Approved
DesipramineThe serum concentration of Odanacatib can be increased when it is combined with Desipramine.Approved
DesloratadineThe serum concentration of Odanacatib can be increased when it is combined with Desloratadine.Approved, Investigational
DexamethasoneThe serum concentration of Odanacatib can be decreased when it is combined with Dexamethasone.Approved, Investigational, Vet Approved
DextromethorphanThe serum concentration of Odanacatib can be increased when it is combined with Dextromethorphan.Approved
DiclofenacThe serum concentration of Odanacatib can be increased when it is combined with Diclofenac.Approved, Vet Approved
DigoxinThe serum concentration of Odanacatib can be decreased when it is combined with Digoxin.Approved
DihydroergotamineThe metabolism of Odanacatib can be decreased when combined with Dihydroergotamine.Approved
DiltiazemThe metabolism of Odanacatib can be decreased when combined with Diltiazem.Approved
DipyridamoleThe serum concentration of Odanacatib can be increased when it is combined with Dipyridamole.Approved
DoxazosinThe serum concentration of Odanacatib can be increased when it is combined with Doxazosin.Approved
DoxepinThe serum concentration of Odanacatib can be increased when it is combined with Doxepin.Approved
DoxorubicinThe serum concentration of Odanacatib can be decreased when it is combined with Doxorubicin.Approved, Investigational
DoxycyclineThe metabolism of Odanacatib can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronabinolThe serum concentration of Odanacatib can be increased when it is combined with Dronabinol.Approved, Illicit
DronedaroneThe metabolism of Odanacatib can be decreased when combined with Dronedarone.Approved
EfavirenzThe metabolism of Odanacatib can be decreased when combined with Efavirenz.Approved, Investigational
ElbasvirThe serum concentration of Odanacatib can be increased when it is combined with Elbasvir.Approved
EnalaprilThe serum concentration of Odanacatib can be increased when it is combined with Enalapril.Approved, Vet Approved
EnasidenibThe serum concentration of Odanacatib can be increased when it is combined with Enasidenib.Approved
EnzalutamideThe serum concentration of Odanacatib can be decreased when it is combined with Enzalutamide.Approved
ErgonovineThe serum concentration of Odanacatib can be increased when it is combined with Ergonovine.Approved
ErgotamineThe serum concentration of Odanacatib can be increased when it is combined with Ergotamine.Approved
ErythromycinThe metabolism of Odanacatib can be decreased when combined with Erythromycin.Approved, Vet Approved
EstramustineThe serum concentration of Odanacatib can be increased when it is combined with Estramustine.Approved
EstriolThe serum concentration of Odanacatib can be decreased when it is combined with Estriol.Approved, Vet Approved
EstroneThe serum concentration of Odanacatib can be decreased when it is combined with Estrone.Approved
EtoposideThe serum concentration of Odanacatib can be increased when it is combined with Etoposide.Approved
EtravirineThe serum concentration of Odanacatib can be increased when it is combined with Etravirine.Approved
FelodipineThe serum concentration of Odanacatib can be increased when it is combined with Felodipine.Approved, Investigational
FentanylThe serum concentration of Odanacatib can be increased when it is combined with Fentanyl.Approved, Illicit, Investigational, Vet Approved
FexofenadineThe serum concentration of Odanacatib can be increased when it is combined with Fexofenadine.Approved
FidaxomicinThe serum concentration of Odanacatib can be increased when it is combined with Fidaxomicin.Approved
FluconazoleThe metabolism of Odanacatib can be decreased when combined with Fluconazole.Approved
FluoxetineThe serum concentration of Odanacatib can be increased when it is combined with Fluoxetine.Approved, Vet Approved
FlupentixolThe serum concentration of Odanacatib can be increased when it is combined with Flupentixol.Approved, Withdrawn
FluphenazineThe serum concentration of Odanacatib can be increased when it is combined with Fluphenazine.Approved
FlurazepamThe serum concentration of Odanacatib can be increased when it is combined with Flurazepam.Approved, Illicit
FluvoxamineThe metabolism of Odanacatib can be decreased when combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe metabolism of Odanacatib can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Odanacatib can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe metabolism of Odanacatib can be increased when combined with Fosphenytoin.Approved
Fusidic AcidThe serum concentration of Odanacatib can be increased when it is combined with Fusidic Acid.Approved
GefitinibThe serum concentration of Odanacatib can be increased when it is combined with Gefitinib.Approved, Investigational
GenisteinThe serum concentration of Odanacatib can be increased when it is combined with Genistein.Investigational
GlecaprevirThe serum concentration of Odanacatib can be increased when it is combined with Glecaprevir.Approved
GlyburideThe serum concentration of Odanacatib can be increased when it is combined with Glyburide.Approved
GlycerinThe serum concentration of Odanacatib can be increased when it is combined with Glycerin.Approved, Investigational
Gramicidin DThe serum concentration of Odanacatib can be increased when it is combined with Gramicidin D.Approved
GrepafloxacinThe serum concentration of Odanacatib can be increased when it is combined with Grepafloxacin.Withdrawn
HaloperidolThe serum concentration of Odanacatib can be increased when it is combined with Haloperidol.Approved
HydrocortisoneThe serum concentration of Odanacatib can be increased when it is combined with Hydrocortisone.Approved, Vet Approved
IdelalisibThe serum concentration of Odanacatib can be increased when it is combined with Idelalisib.Approved
ImatinibThe metabolism of Odanacatib can be decreased when combined with Imatinib.Approved
ImipramineThe serum concentration of Odanacatib can be increased when it is combined with Imipramine.Approved
IndinavirThe metabolism of Odanacatib can be decreased when combined with Indinavir.Approved
IndomethacinThe serum concentration of Odanacatib can be increased when it is combined with Indomethacin.Approved, Investigational
IrbesartanThe metabolism of Odanacatib can be decreased when combined with Irbesartan.Approved, Investigational
IsavuconazoniumThe metabolism of Odanacatib can be decreased when combined with Isavuconazonium.Approved, Investigational
IsradipineThe metabolism of Odanacatib can be decreased when combined with Isradipine.Approved
ItraconazoleThe metabolism of Odanacatib can be decreased when combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Odanacatib can be increased when it is combined with Ivacaftor.Approved
IvermectinThe serum concentration of Odanacatib can be increased when it is combined with Ivermectin.Approved, Vet Approved
KetamineThe serum concentration of Odanacatib can be increased when it is combined with Ketamine.Approved, Vet Approved
KetoconazoleThe metabolism of Odanacatib can be decreased when combined with Ketoconazole.Approved, Investigational
LansoprazoleThe serum concentration of Odanacatib can be increased when it is combined with Lansoprazole.Approved, Investigational
LapatinibThe serum concentration of Odanacatib can be increased when it is combined with Lapatinib.Approved, Investigational
LevofloxacinThe serum concentration of Odanacatib can be increased when it is combined with Levofloxacin.Approved, Investigational
LevothyroxineThe serum concentration of Odanacatib can be decreased when it is combined with Levothyroxine.Approved
LidocaineThe serum concentration of Odanacatib can be increased when it is combined with Lidocaine.Approved, Vet Approved
LiothyronineThe serum concentration of Odanacatib can be decreased when it is combined with Liothyronine.Approved, Vet Approved
LiotrixThe serum concentration of Odanacatib can be decreased when it is combined with Liotrix.Approved
LisinoprilThe serum concentration of Odanacatib can be increased when it is combined with Lisinopril.Approved, Investigational
LomitapideThe serum concentration of Odanacatib can be increased when it is combined with Lomitapide.Approved
LoperamideThe serum concentration of Odanacatib can be increased when it is combined with Loperamide.Approved
LopinavirThe metabolism of Odanacatib can be decreased when combined with Lopinavir.Approved
LoratadineThe serum concentration of Odanacatib can be increased when it is combined with Loratadine.Approved
LosartanThe serum concentration of Odanacatib can be increased when it is combined with Losartan.Approved
LovastatinThe metabolism of Odanacatib can be decreased when combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of Odanacatib can be increased when it is combined with Luliconazole.Approved
LumacaftorThe serum concentration of Odanacatib can be increased when it is combined with Lumacaftor.Approved
MaprotilineThe serum concentration of Odanacatib can be increased when it is combined with Maprotiline.Approved
MebendazoleThe serum concentration of Odanacatib can be increased when it is combined with Mebendazole.Approved, Vet Approved
MefloquineThe serum concentration of Odanacatib can be increased when it is combined with Mefloquine.Approved
Megestrol acetateThe serum concentration of Odanacatib can be increased when it is combined with Megestrol acetate.Approved, Vet Approved
MeprobamateThe serum concentration of Odanacatib can be increased when it is combined with Meprobamate.Approved, Illicit
MethadoneThe serum concentration of Odanacatib can be increased when it is combined with Methadone.Approved
MetoprololThe serum concentration of Odanacatib can be increased when it is combined with Metoprolol.Approved, Investigational
MibefradilThe serum concentration of Odanacatib can be increased when it is combined with Mibefradil.Withdrawn
MiconazoleThe serum concentration of Odanacatib can be increased when it is combined with Miconazole.Approved, Investigational, Vet Approved
MidazolamThe serum concentration of Odanacatib can be decreased when it is combined with Midazolam.Approved, Illicit
MifepristoneThe serum concentration of Odanacatib can be increased when it is combined with Mifepristone.Approved, Investigational
MitomycinThe serum concentration of Odanacatib can be increased when it is combined with Mitomycin.Approved
MitotaneThe serum concentration of Odanacatib can be decreased when it is combined with Mitotane.Approved
MitoxantroneThe serum concentration of Odanacatib can be decreased when it is combined with Mitoxantrone.Approved, Investigational
MorphineThe serum concentration of Odanacatib can be increased when it is combined with Morphine.Approved, Investigational
NaltrexoneThe serum concentration of Odanacatib can be increased when it is combined with Naltrexone.Approved, Investigational, Vet Approved
NaringeninThe serum concentration of Odanacatib can be increased when it is combined with Naringenin.Experimental
NefazodoneThe metabolism of Odanacatib can be decreased when combined with Nefazodone.Approved, Withdrawn
NelfinavirThe metabolism of Odanacatib can be decreased when combined with Nelfinavir.Approved
NeostigmineThe serum concentration of Odanacatib can be increased when it is combined with Neostigmine.Approved, Vet Approved
NetupitantThe serum concentration of Odanacatib can be increased when it is combined with Netupitant.Approved
NevirapineThe metabolism of Odanacatib can be increased when combined with Nevirapine.Approved
NicardipineThe serum concentration of Odanacatib can be increased when it is combined with Nicardipine.Approved
NifedipineThe serum concentration of Odanacatib can be decreased when it is combined with Nifedipine.Approved
NilotinibThe metabolism of Odanacatib can be decreased when combined with Nilotinib.Approved, Investigational
NisoldipineThe serum concentration of Odanacatib can be increased when it is combined with Nisoldipine.Approved
NitrazepamThe serum concentration of Odanacatib can be increased when it is combined with Nitrazepam.Approved
NitrendipineThe serum concentration of Odanacatib can be increased when it is combined with Nitrendipine.Approved
NorethisteroneThe serum concentration of Odanacatib can be decreased when it is combined with Norethisterone.Approved
OlaparibThe metabolism of Odanacatib can be decreased when combined with Olaparib.Approved
OmeprazoleThe serum concentration of Odanacatib can be increased when it is combined with Omeprazole.Approved, Investigational, Vet Approved
OsimertinibThe serum concentration of Odanacatib can be increased when it is combined with Osimertinib.Approved
P-NitrophenolThe serum concentration of Odanacatib can be increased when it is combined with P-Nitrophenol.Experimental
PaclitaxelThe serum concentration of Odanacatib can be increased when it is combined with Paclitaxel.Approved, Vet Approved
PalbociclibThe serum concentration of Odanacatib can be increased when it is combined with Palbociclib.Approved
Palmitic AcidThe serum concentration of Odanacatib can be increased when it is combined with Palmitic Acid.Experimental
PantoprazoleThe serum concentration of Odanacatib can be increased when it is combined with Pantoprazole.Approved
ParoxetineThe serum concentration of Odanacatib can be increased when it is combined with Paroxetine.Approved, Investigational
PentobarbitalThe metabolism of Odanacatib can be increased when combined with Pentobarbital.Approved, Vet Approved
PerindoprilThe serum concentration of Odanacatib can be increased when it is combined with Perindopril.Approved
PhenobarbitalThe metabolism of Odanacatib can be increased when combined with Phenobarbital.Approved
PhenytoinThe metabolism of Odanacatib can be increased when combined with Phenytoin.Approved, Vet Approved
PibrentasvirThe serum concentration of Odanacatib can be increased when it is combined with Pibrentasvir.Approved
PimozideThe serum concentration of Odanacatib can be increased when it is combined with Pimozide.Approved
PioglitazoneThe metabolism of Odanacatib can be decreased when combined with Pioglitazone.Approved, Investigational
Platelet Activating FactorThe serum concentration of Odanacatib can be decreased when it is combined with Platelet Activating Factor.Experimental
PonatinibThe serum concentration of Odanacatib can be increased when it is combined with Ponatinib.Approved
PosaconazoleThe metabolism of Odanacatib can be decreased when combined with Posaconazole.Approved, Investigational, Vet Approved
PravastatinThe serum concentration of Odanacatib can be increased when it is combined with Pravastatin.Approved
PrazosinThe serum concentration of Odanacatib can be increased when it is combined with Prazosin.Approved
PrednisoneThe serum concentration of Odanacatib can be increased when it is combined with Prednisone.Approved, Vet Approved
PrimidoneThe metabolism of Odanacatib can be increased when combined with Primidone.Approved, Vet Approved
ProbenecidThe serum concentration of Odanacatib can be increased when it is combined with Probenecid.Approved
ProgesteroneThe serum concentration of Odanacatib can be decreased when it is combined with Progesterone.Approved, Vet Approved
PromethazineThe serum concentration of Odanacatib can be increased when it is combined with Promethazine.Approved
PropafenoneThe serum concentration of Odanacatib can be increased when it is combined with Propafenone.Approved
PropranololThe serum concentration of Odanacatib can be increased when it is combined with Propranolol.Approved, Investigational
ProtriptylineThe serum concentration of Odanacatib can be increased when it is combined with Protriptyline.Approved
QuercetinThe serum concentration of Odanacatib can be increased when it is combined with Quercetin.Experimental
QuinacrineThe serum concentration of Odanacatib can be increased when it is combined with Quinacrine.Approved
QuinidineThe serum concentration of Odanacatib can be increased when it is combined with Quinidine.Approved
QuinineThe serum concentration of Odanacatib can be increased when it is combined with Quinine.Approved
RabeprazoleThe metabolism of Odanacatib can be decreased when combined with Rabeprazole.Approved, Investigational
RanitidineThe serum concentration of Odanacatib can be increased when it is combined with Ranitidine.Approved
RanolazineThe serum concentration of Odanacatib can be increased when it is combined with Ranolazine.Approved, Investigational
ReboxetineThe serum concentration of Odanacatib can be increased when it is combined with Reboxetine.Approved, Investigational
RegorafenibThe serum concentration of Odanacatib can be increased when it is combined with Regorafenib.Approved
ReserpineThe serum concentration of Odanacatib can be decreased when it is combined with Reserpine.Approved
RifabutinThe metabolism of Odanacatib can be increased when combined with Rifabutin.Approved
RifampicinThe metabolism of Odanacatib can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Odanacatib can be increased when combined with Rifapentine.Approved
RilpivirineThe serum concentration of Odanacatib can be increased when it is combined with Rilpivirine.Approved
RitonavirThe metabolism of Odanacatib can be decreased when combined with Ritonavir.Approved, Investigational
RolapitantThe serum concentration of Odanacatib can be increased when it is combined with Rolapitant.Approved
RosiglitazoneThe metabolism of Odanacatib can be decreased when combined with Rosiglitazone.Approved, Investigational
SaquinavirThe metabolism of Odanacatib can be decreased when combined with Saquinavir.Approved, Investigational
ScopolamineThe serum concentration of Odanacatib can be increased when it is combined with Scopolamine.Approved
SecobarbitalThe metabolism of Odanacatib can be increased when combined with Secobarbital.Approved, Vet Approved
SelegilineThe serum concentration of Odanacatib can be increased when it is combined with Selegiline.Approved, Investigational, Vet Approved
SertralineThe serum concentration of Odanacatib can be increased when it is combined with Sertraline.Approved
SildenafilThe metabolism of Odanacatib can be decreased when combined with Sildenafil.Approved, Investigational
SiltuximabThe serum concentration of Odanacatib can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Odanacatib can be increased when it is combined with Simeprevir.Approved
SimvastatinThe serum concentration of Odanacatib can be increased when it is combined with Simvastatin.Approved
SirolimusThe serum concentration of Odanacatib can be decreased when it is combined with Sirolimus.Approved, Investigational
SorafenibThe serum concentration of Odanacatib can be increased when it is combined with Sorafenib.Approved, Investigational
SpironolactoneThe serum concentration of Odanacatib can be increased when it is combined with Spironolactone.Approved
St. John's WortThe serum concentration of Odanacatib can be decreased when it is combined with St. John's Wort.Nutraceutical
StaurosporineThe serum concentration of Odanacatib can be increased when it is combined with Staurosporine.Experimental
StiripentolThe serum concentration of Odanacatib can be increased when it is combined with Stiripentol.Approved
StreptozocinThe serum concentration of Odanacatib can be decreased when it is combined with Streptozocin.Approved
SulfamethoxazoleThe metabolism of Odanacatib can be decreased when combined with Sulfamethoxazole.Approved
SulfinpyrazoneThe serum concentration of Odanacatib can be increased when it is combined with Sulfinpyrazone.Approved
SulfisoxazoleThe metabolism of Odanacatib can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
SumatriptanThe serum concentration of Odanacatib can be increased when it is combined with Sumatriptan.Approved, Investigational
SunitinibThe serum concentration of Odanacatib can be increased when it is combined with Sunitinib.Approved, Investigational
TacrineThe serum concentration of Odanacatib can be increased when it is combined with Tacrine.Withdrawn
TacrolimusThe serum concentration of Odanacatib can be decreased when it is combined with Tacrolimus.Approved, Investigational
TamoxifenThe serum concentration of Odanacatib can be decreased when it is combined with Tamoxifen.Approved
Taurocholic AcidThe serum concentration of Odanacatib can be increased when it is combined with Taurocholic Acid.Experimental
TelaprevirThe metabolism of Odanacatib can be decreased when combined with Telaprevir.Withdrawn
TelithromycinThe metabolism of Odanacatib can be decreased when combined with Telithromycin.Approved
TelmisartanThe serum concentration of Odanacatib can be increased when it is combined with Telmisartan.Approved, Investigational
TemsirolimusThe serum concentration of Odanacatib can be increased when it is combined with Temsirolimus.Approved
TerazosinThe serum concentration of Odanacatib can be increased when it is combined with Terazosin.Approved
TerfenadineThe serum concentration of Odanacatib can be increased when it is combined with Terfenadine.Withdrawn
TeriflunomideThe metabolism of Odanacatib can be decreased when combined with Teriflunomide.Approved
TesmilifeneThe serum concentration of Odanacatib can be decreased when it is combined with Tesmilifene.Investigational
TestosteroneThe serum concentration of Odanacatib can be increased when it is combined with Testosterone.Approved, Investigational
TicagrelorThe serum concentration of Odanacatib can be increased when it is combined with Ticagrelor.Approved
TiclopidineThe metabolism of Odanacatib can be decreased when combined with Ticlopidine.Approved
TocilizumabThe serum concentration of Odanacatib can be decreased when it is combined with Tocilizumab.Approved
TolvaptanThe serum concentration of Odanacatib can be increased when it is combined with Tolvaptan.Approved
TopiroxostatThe metabolism of Odanacatib can be decreased when combined with Topiroxostat.Approved
TrazodoneThe serum concentration of Odanacatib can be decreased when it is combined with Trazodone.Approved, Investigational
TrifluoperazineThe serum concentration of Odanacatib can be increased when it is combined with Trifluoperazine.Approved
TriflupromazineThe serum concentration of Odanacatib can be increased when it is combined with Triflupromazine.Approved, Vet Approved
TrimethoprimThe serum concentration of Odanacatib can be decreased when it is combined with Trimethoprim.Approved, Vet Approved
TrimipramineThe serum concentration of Odanacatib can be increased when it is combined with Trimipramine.Approved
TroleandomycinThe serum concentration of Odanacatib can be increased when it is combined with Troleandomycin.Approved
VelpatasvirThe serum concentration of Odanacatib can be increased when it is combined with Velpatasvir.Approved
VenlafaxineThe metabolism of Odanacatib can be decreased when combined with Venlafaxine.Approved
VerapamilThe metabolism of Odanacatib can be decreased when combined with Verapamil.Approved
VinblastineThe serum concentration of Odanacatib can be decreased when it is combined with Vinblastine.Approved
VincristineThe serum concentration of Odanacatib can be decreased when it is combined with Vincristine.Approved, Investigational
VinorelbineThe serum concentration of Odanacatib can be increased when it is combined with Vinorelbine.Approved, Investigational
VoriconazoleThe metabolism of Odanacatib can be decreased when combined with Voriconazole.Approved, Investigational
VoxilaprevirThe serum concentration of Odanacatib can be increased when it is combined with Voxilaprevir.Approved
ZimelidineThe serum concentration of Odanacatib can be increased when it is combined with Zimelidine.Withdrawn
ZiprasidoneThe metabolism of Odanacatib can be decreased when combined with Ziprasidone.Approved
Food Interactions
Not Available

References

Synthesis Reference
Not Available
General References
  1. Mullard A: Merck &Co. drops osteoporosis drug odanacatib. Nat Rev Drug Discov. 2016 Sep 29;15(10):669. doi: 10.1038/nrd.2016.207. [PubMed:27681784]
  2. 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. [PubMed:24276460]
  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. [PubMed:27402726]
  4. 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. [PubMed:24553380]
  5. 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. [PubMed:22228398]
  6. 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. [PubMed:18226527]
  7. Black WC: Peptidomimetic inhibitors of cathepsin K. Curr Top Med Chem. 2010;10(7):745-51. [PubMed:20337585]
External Links
ChemSpider
8328162
BindingDB
50255753
ChEMBL
CHEMBL481611
Wikipedia
Odanacatib
ATC Codes
Not Available
AHFS Codes
Not Available
PDB Entries
Not Available
FDA label
Not Available
MSDS
Download (25.4 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentHepatic Insufficiency1
1CompletedTreatmentImpaired Renal Function1
1CompletedTreatmentBone destruction5
1TerminatedTreatmentBone destruction1
2CompletedTreatmentCancer, Breast / Metastatic Bone Disease1
2CompletedTreatmentPostmenopausal Osteoporosis (PMO)1
2CompletedTreatmentBone destruction2
2TerminatedTreatmentSynovitis of osteoarthritis1
3CompletedTreatmentPostmenopausal Osteoporosis (PMO)1
3CompletedTreatmentBone destruction2
3TerminatedTreatmentBone destruction1
3WithdrawnPreventionCancer, Breast1
3WithdrawnPreventionProstate Cancer1
3WithdrawnTreatmentBone destruction / Postmenopausal Osteoporosis (PMO)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
PropertyValueSource
Water Solubility0.00666 mg/mLALOGPS
logP4.04ALOGPS
logP3.33ChemAxon
logS-4.9ALOGPS
pKa (Strongest Acidic)11.12ChemAxon
pKa (Strongest Basic)3.25ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area99.06 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity126.95 m3·mol-1ChemAxon
Polarizability50.35 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

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
Leucine or derivatives / Alpha-amino acid amide / Biphenyl / Benzenesulfonyl group / Aralkylamine / Monocyclic benzene moiety / Fatty amide / N-acyl-amine / Fatty acyl / Benzenoid
show 23 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
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
  1. 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. [PubMed:18226527]

Enzymes

Kind
Protein
Organism
Human
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
  1. 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. [PubMed:24553380]
Kind
Protein
Organism
Human
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
  1. 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. [PubMed:24553380]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
No
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
  1. 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. [PubMed:24553380]

Drug created on March 19, 2008 10:47 / Updated on October 02, 2017 05:45