ODANACATIB

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C25H27F4N3O3S
Molecular Weight	525.559
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=FWIVDMJALNEADT-SFTDATJTSA-N

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

HIDE SMILES / InChI

Molecular Formula	C25H27F4N3O3S
Molecular Weight	525.559
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://adisinsight.springer.com/drugs/800024552
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/18226527 | https://www.ncbi.nlm.nih.gov/pubmed/27681784

Odanacatib is a potent, selective, and neutral cathepsin K inhibitor, an enzyme involved in bone resorption. Merck & Co was developing odanacatib, a once-weekly, oral Odanacatib, for the treatment of postmenopausal osteoporosis and osteoporosis in men. Merck & Co. has discontinued development of its cathepsin K inhibitor odanacatib, citing an increased risk of cardiovascular events for the osteoporosis drug.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Cathepsin K 4 Target ID: CHEMBL268 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18226527	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Postmenopausal osteoporosis 59 Sources: http://adisinsight.springer.com/drugs/800024552	Primary	Phase III 656	Unknown Approved Use Unknown
Osteoporosis 97 Sources: http://adisinsight.springer.com/drugs/800024552	Primary	Phase III 656	Unknown Approved Use Unknown
Breast cancer 434 Sources: http://adisinsight.springer.com/drugs/800024552	Primary	Phase III 656	Unknown Approved Use Unknown
Osteoarthritis 157 Sources: http://adisinsight.springer.com/drugs/800024552	Primary	Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
839.2 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23013236	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:		ODANACATIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: HIGH-FAT
154.7 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23013236	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:		ODANACATIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
477.3 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23013236	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:		ODANACATIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
1.76 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23013236	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		ODANACATIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: HIGH-FAT
2.23 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23013236	-0.01 mg single, oral dose: -0.01 mg route of administration: Oral experiment type: SINGLE co-administered:		ODANACATIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: HIGH-FAT
353.5 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23013236	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		ODANACATIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
56.2 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27402726	1 mg single, intravenous dose: 1 mg route of administration: Intravenous experiment type: SINGLE co-administered: ODANACATIB	ODANACATIB	ODANACATIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
1.82 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23013236	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:		ODANACATIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: HIGH-FAT

AUC

Value	Dose	Co-administered	Analyte	Population
16.1 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23013236	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:		ODANACATIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: HIGH-FAT
3.2 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23013236	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:		ODANACATIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
9.4 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23013236	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:		ODANACATIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
1.73 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23013236	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		ODANACATIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: HIGH-FAT
2.11 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23013236	-0.01 mg single, oral dose: -0.01 mg route of administration: Oral experiment type: SINGLE co-administered:		ODANACATIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: HIGH-FAT
6.4 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23013236	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		ODANACATIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
2.7 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27402726	1 mg single, intravenous dose: 1 mg route of administration: Intravenous experiment type: SINGLE co-administered: ODANACATIB	ODANACATIB	ODANACATIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
1.87 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23013236	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:		ODANACATIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: HIGH-FAT

T_1/2

Value	Dose	Co-administered	Analyte	Population
62.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23013236	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:		ODANACATIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: HIGH-FAT
59.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23013236	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:		ODANACATIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
48.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23013236	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		ODANACATIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: HIGH-FAT
104.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27402726	1 mg single, intravenous dose: 1 mg route of administration: Intravenous experiment type: SINGLE co-administered: ODANACATIB	ODANACATIB	ODANACATIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
50.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23013236	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:		ODANACATIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: HIGH-FAT

Doses

Dose	Population	Adverse events
50 mg 1 times / week multiple, oral (unknown) Studied dose Dose: 50 mg, 1 times / week Route: oral Route: multiple Dose: 50 mg, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/33200257	unhealthy, ADULT n = 146 Health Status: unhealthy Condition: osteoporosis Age Group: ADULT Sex: M Food Status: UNKNOWN Population Size: 146 Sources: https://pubmed.ncbi.nlm.nih.gov/33200257	Disc. AE: Myalgia... AEs leading to discontinuation/dose reduction: Myalgia (0.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/33200257
300 mg 1 times / day multiple, oral (starting) Highest recorded dose Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/31175709	healthy n = 56 Health Status: healthy Sex: M+F Food Status: FASTED Population Size: 56 Sources: https://pubmed.ncbi.nlm.nih.gov/31175709	Other AEs: Abdominal pain, Application-site erosion... Other AEs: Abdominal pain (5.4%) Application-site erosion (5.4%) Application-site erythema (17.9%) Pruritus (7.1%) Sources: https://pubmed.ncbi.nlm.nih.gov/31175709
50 mg 1 times / week multiple, oral (unknown) Studied dose Dose: 50 mg, 1 times / week Route: oral Route: multiple Dose: 50 mg, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/26879200	unhealthy n = 28 Health Status: unhealthy Condition: low bone mineral density Sex: F Food Status: UNKNOWN Population Size: 28 Sources: https://pubmed.ncbi.nlm.nih.gov/26879200	Disc. AE: Basal cell carcinoma... AEs leading to discontinuation/dose reduction: Basal cell carcinoma (3.6%) Sources: https://pubmed.ncbi.nlm.nih.gov/26879200

AEs

AE	Significance	Dose	Population
Myalgia	0.7% Disc. AE	50 mg 1 times / week multiple, oral (unknown) Studied dose Dose: 50 mg, 1 times / week Route: oral Route: multiple Dose: 50 mg, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/33200257	unhealthy, ADULT n = 146 Health Status: unhealthy Condition: osteoporosis Age Group: ADULT Sex: M Food Status: UNKNOWN Population Size: 146 Sources: https://pubmed.ncbi.nlm.nih.gov/33200257
Application-site erythema	17.9%	300 mg 1 times / day multiple, oral (starting) Highest recorded dose Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/31175709	healthy n = 56 Health Status: healthy Sex: M+F Food Status: FASTED Population Size: 56 Sources: https://pubmed.ncbi.nlm.nih.gov/31175709
Abdominal pain	5.4%	300 mg 1 times / day multiple, oral (starting) Highest recorded dose Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/31175709	healthy n = 56 Health Status: healthy Sex: M+F Food Status: FASTED Population Size: 56 Sources: https://pubmed.ncbi.nlm.nih.gov/31175709
Application-site erosion	5.4%	300 mg 1 times / day multiple, oral (starting) Highest recorded dose Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/31175709	healthy n = 56 Health Status: healthy Sex: M+F Food Status: FASTED Population Size: 56 Sources: https://pubmed.ncbi.nlm.nih.gov/31175709
Pruritus	7.1%	300 mg 1 times / day multiple, oral (starting) Highest recorded dose Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/31175709	healthy n = 56 Health Status: healthy Sex: M+F Food Status: FASTED Population Size: 56 Sources: https://pubmed.ncbi.nlm.nih.gov/31175709
Basal cell carcinoma	3.6% Disc. AE	50 mg 1 times / week multiple, oral (unknown) Studied dose Dose: 50 mg, 1 times / week Route: oral Route: multiple Dose: 50 mg, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/26879200	unhealthy n = 28 Health Status: unhealthy Condition: low bone mineral density Sex: F Food Status: UNKNOWN Population Size: 28 Sources: https://pubmed.ncbi.nlm.nih.gov/26879200

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inhibitor 1587	inhibitor 1767		inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2C19 1478	CYP2C8 693 P-gp 1537

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/24142206/	no	yes (co-administration study) Comment: Coadministration did not affect R( )- and S(-)-warfarin exposure. Sources: https://pubmed.ncbi.nlm.nih.gov/24142206/
CYP2C19 1553	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/24142206/	no	yes (co-administration study) Comment: Coadministration did not affect R( )- and S(-)-warfarin exposure. Sources: https://pubmed.ncbi.nlm.nih.gov/24142206/
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/24142206/	no	yes (co-administration study) Comment: Coadministration did not affect R( )- and S(-)-warfarin exposure. Sources: https://pubmed.ncbi.nlm.nih.gov/24142206/
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/24142206/	no	yes (co-administration study) Comment: Coadministration did not affect R( )- and S(-)-warfarin exposure. Sources: https://pubmed.ncbi.nlm.nih.gov/24142206/

Drug as victim

Target	Modality	Activity
CYP3A4 1737	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24553380/	major
CYP2C8 693	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24553380/	minor
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24553380/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/31175709/

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY105556	https://www.001chemical.com/chem/search?q=DY105556
1PlusChem LLC	1P003A9R	https://www.1pchem.com/search?query=1P003A9R
A2B Chem	AB52479	http://a2bchem.com/prod/AB52479
AChemBlock	10356	http://www.achemblock.com/catalogsearch/result/?q=10356
AK Scientific	Y0388	https://aksci.com/item_detail.php?cat=Y0388
Aceschem	ACF023007	https://www.aceschem.com/catalog/search.do?q=ACF023007
Angene	AGN-PC-0SVOB7	http://www.angenechemical.com/productshow/AGN-PC-0SVOB7.html
ApexBio Technology	A2487	https://www.apexbt.com/catalogsearch/result/?q=A2487
AstaTech	83152	http://astatechinc.com/CPSResult.php?CRNO=83152
Axon MedChem	1771	https://www.axonmedchem.com/product/1771
BLD Pharm	BD242186	http://www.bldpharm.com/search/Search.html?keyword=BD242186
BOC Sciences	603139-19-1	http://www.bocsci.com/description.asp?cas=603139-19-1
Cayman Chemical	21466	http://www.caymanchem.com/app/template/Product.vm/catalog/21466
Chem Scene	CS-0277	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0277
ChemShuttle	104830	https://www.chemshuttle.com/catalogsearch/result/?q=104830
Combi-Blocks	QK-7612	http://www.combi-blocks.com/cgi-bin/find.cgi?QK-7612
KeyOrganics	AS-19562	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-19562
Lab Seeker	SC-69096	http://www.labseeker.com/search.php?keywords=SC-69096&category=0
LabSeeker	SC-69096	http://www.labseeker.com/search.php?keywords=SC-69096&category=0
Matrix Scientific	125269	http://www.matrixscientific.com/125269.html
MedChem Express	HY-10042	https://www.medchemexpress.com/search.html?q=HY-10042&ft=&fa=&fp=
MolPort	MolPort-021-804-981	https://www.molport.com/shop/molecule-link/MolPort-021-804-981
Molcore	MC105556	http://www.molcore.com/CatMC105556.html
Molnova	M15252	https://www.molnova.com/en/serch-list.html?keywords=M15252
MuseChem	I004270	https://www.musechem.com/product/I004270.html
ShangHai Biochempartner	BCP000132	http://www.biochempartner.com/search_BCP000132
Synovel	SN-0270	http://www.synovellab.com/?s=SN-0270&submit=Search
Synthonix	14866	https://synthonix.com/catalogsearch/result/?q=14866
TargetMol	T6035	https://www.targetmol.com/search?keyword=T6035
Tetrahedron	TS90038	http://www.thsci.com/search.do?q=TS90038
eMolecules	108759429	https://orderbb.emolecules.com/search/#?query=108759429
eMolecules	275178454	https://orderbb.emolecules.com/search/#?query=275178454
eMolecules	300651548	https://orderbb.emolecules.com/search/#?query=300651548
eMolecules	42777428	https://orderbb.emolecules.com/search/#?query=42777428
eNovation Chemicals	D596979	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D596979&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-6871213580	https://mcule.com/MCULE-6871213580/
mcule	MCULE-8587680000	https://mcule.com/MCULE-8587680000/

PubMed

Title	Date	PubMed
The discovery of odanacatib (MK-0822), a selective inhibitor of cathepsin K.	2008 Feb 1	18226527
Bone density, turnover, and estimated strength in postmenopausal women treated with odanacatib: a randomized trial.	2013 Feb	23337728

Patents

Sample Use Guides

In Vivo Use Guide

Merck is conducting a long-term phase II trial that is assessing four different doses of odanacatib (3mg, 10mg, 25mg and 50mg once-weekly for 2 years) in women with postmenopausal osteoporosis (NCT00112437; EudraCT2005-001511-22). Results from this phase IIb study showed that odanacatib 50mg increased bone mineral density (BMD) from baseline, and was generally safe and well tolerated.

Route of Administration: Oral

In Vitro Use Guide

1 nM odanacatib had suppressive effects on the expression levels of inflammatory cytokines in murine RAW 264.7 cells were cultured in the presence of the receptor activator of NF-kB and lipopolysaccharide

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:06:13 GMT 2023` Edited by `admin` on `Fri Dec 15 16:06:13 GMT 2023`
Record UNII	N673F6W2VH
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ODANACATIB

Official Name

English

MK0822

Code

English

ODANACATIB [USAN]

Common Name

English

ODANACATIB [MI]

Common Name

English

ODANACATIB [MART.]

Common Name

English

ODANACATIB [JAN]

Common Name

English

MK-0822

Code

English

odanacatib [INN]

Common Name

English

Odanacatib [WHO-DD]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C67439