Odanacatib

Summary

Odanacatib (CHEMBL481611) is a phase-3 clinical-stage small molecule targeting CTSK, CTSS, and CTSZ; indicated across 6 conditions including osteoporosis and postmenopausal osteoporosis.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 3 (CTSK, CTSS, CTSZ)
• Indications: 6 conditions
• Clinical trials: 20
• Chemistry: 525.6 Da · C25H27F4N3O3S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL481611
Name	Odanacatib
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	10152654
Molecular formula	C25H27F4N3O3S
Molecular weight	525.6
InChIKey	FWIVDMJALNEADT-SFTDATJTSA-N

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

IUPAC name: (2S)-N-(1-cyanocyclopropyl)-4-fluoro-4-methyl-2-[[(1S)-2,2,2-trifluoro-1-[4-(4-methylsulfonylphenyl)phenyl]ethyl]amino]pentanamide

Also known as: L-001037536, L-1037536, MK-0822, MK0822, Odanacatib, ODANACATIB, odanacatib, SID174006242, ODANACATIB (MK 0822), Odanacatib (MK 0822)

Patent coverage: 309 distinct patent families (804 SureChEMBL compound mentions), from 1 matched compound structure(s). Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
CTSK	cathepsin K	Inhibition	9.7	1.7%	P43235
CTSS	cathepsin S	Inhibition	7.22	0.6%	P25774
CTSZ	cathepsin Z	Inhibition	8	0.2%	Q9UBR2

Broader ChEMBL bioactivity targets: 8 (assay-derived). Sample: Cathepsin F, Cathepsin K, Cathepsin S, Cathepsin L2, Cathepsin K, Cruzipain, Procathepsin L, Cathepsin B.

Bioactivity

ChEMBL activities: 21 potent at pChembl ≥ 5 of 21 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
CTSK	9.74	Ki	0.18	nM	CHEMBL_ACT_18695110
CTSK	9.7	IC50	0.2	nM	CHEMBL_ACT_2078031
CTSK	9.7	IC50	0.2	nM	CHEMBL_ACT_2078094
CTSK	9.7	IC50	0.2	nM	CHEMBL_ACT_2491146
CTSK	9.7	Ki	0.2	nM	CHEMBL_ACT_26041562
CTSK	9.7	IC50	0.2	nM	CHEMBL_ACT_3092482
CTSK	9.7	IC50	0.2	nM	CHEMBL_ACT_3302255
CTSK	9.7	IC50	0.2	nM	CHEMBL_ACT_5195288
P43236	9	IC50	1	nM	CHEMBL_ACT_2078096
CTSK	8.77	IC50	1.7	nM	CHEMBL_ACT_24969121
CTSS	7.35	IC50	45	nM	CHEMBL_ACT_2078111
CTSS	7.22	IC50	60	nM	CHEMBL_ACT_2078067
P25779	6.9	Ki	125.9	nM	CHEMBL_ACT_18858983
CTSS	6.74	IC50	183	nM	CHEMBL_ACT_12093225
CTSV	6.12	IC50	762	nM	CHEMBL_ACT_2078084
CTSF	6.1	IC50	795	nM	CHEMBL_ACT_2078083
CTSB	5.99	IC50	1034	nM	CHEMBL_ACT_2078043
CTSB	5.98	IC50	1050	nM	CHEMBL_ACT_2078105
CTSL	5.9	Ki	1259	nM	CHEMBL_ACT_18859002
CTSL	5.52	IC50	2995	nM	CHEMBL_ACT_2078055
CTSL	5.32	IC50	4843	nM	CHEMBL_ACT_2078108

Target pathways

Aggregated over 3 target gene(s): CTSK, CTSS, CTSZ.

Top Reactome pathways

36 total, by targets touching each:

Pathway	Targets	Genes
Innate Immune System	3	CTSK, CTSS, CTSZ
Immune System	3	CTSK, CTSS, CTSZ
Adaptive Immune System	2	CTSK, CTSS
Degradation of the extracellular matrix	2	CTSK, CTSS
Extracellular matrix organization	2	CTSK, CTSS
Trafficking and processing of endosomal TLR	2	CTSK, CTSS
Toll-like Receptor Cascades	2	CTSK, CTSS
MHC class II antigen presentation	2	CTSK, CTSS
Neutrophil degranulation	2	CTSS, CTSZ
Antigen processing-Cross presentation	1	CTSS
Endosomal/Vacuolar pathway	1	CTSS
Collagen degradation	1	CTSK
Collagen formation	1	CTSS
Activation of Matrix Metalloproteinases	1	CTSK
ER to Golgi Anterograde Transport	1	CTSZ
Membrane Trafficking	1	CTSZ
trans-Golgi Network Vesicle Budding	1	CTSZ
Assembly of collagen fibrils and other multimeric structures	1	CTSS
Metabolism of Angiotensinogen to Angiotensins	1	CTSZ
COPII-mediated vesicle transport	1	CTSZ
Generic Transcription Pathway	1	CTSK
Peptide hormone metabolism	1	CTSZ
Metabolism of proteins	1	CTSZ
Lysosome Vesicle Biogenesis	1	CTSZ
Asparagine N-linked glycosylation	1	CTSZ
Vesicle-mediated transport	1	CTSZ
Cargo concentration in the ER	1	CTSZ
Post-translational protein modification	1	CTSZ
RNA Polymerase II Transcription	1	CTSK
Gene expression (Transcription)	1	CTSK

Dominant GO biological processes

GO term	Targets
proteolysis	3
obsolete proteolysis involved in protein catabolic process	3
extracellular matrix disassembly	2
collagen catabolic process	2
antigen processing and presentation of exogenous peptide antigen via MHC class II	2
mitophagy	1
thyroid hormone generation	1
bone resorption	1
negative regulation of cartilage development	1
toll-like receptor signaling pathway	1
adaptive immune response	1
regulation of antigen processing and presentation	1
immune response	1
response to acidic pH	1
protein processing	1

Indications & clinical

Indications

6 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
osteoporosis	3	MONDO:0005298	EFO:0003882
postmenopausal osteoporosis	3	MONDO:0008159	EFO:0003854
breast neoplasm	3	MONDO:0021100	MONDO:0007254
osteoarthritis	2	MONDO:0005178	MONDO:0005178
kidney failure	1	MONDO:0001106	HP:0000083

1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 20.

Phase distribution

Phase	Trials
PHASE1	8
PHASE3	7
PHASE2	5

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00529373	PHASE3	TERMINATED	A Study of MK-0822 in Postmenopausal Women With Osteoporosis to Assess Fracture Risk (MK-0822-018)
NCT00691899	PHASE3	WITHDRAWN	A Study to Assess the Effects of MK0822 in Prolonging Time to First Bone Metastasis in Men With Castration-Resistant Prostate Cancer (0822-030)
NCT00692458	PHASE3	WITHDRAWN	A Study to Assess the Effects of MK0822 in Reducing the Risk of Bone Metastasis in Women With Breast Cancer (0822-029)
NCT00729183	PHASE3	COMPLETED	Study to Evaluate Efficacy of Odanacatib (MK-0822) on Bone Mineral Density (BMD) and Bone Micro-architecture and Overall Safety in Postmenopausal Women (MK-0822-031)
NCT01120600	PHASE3	COMPLETED	A Study to Assess Safety and Efficacy of Odanacatib (MK-0822) in Men With Osteoporosis (MK-0822-053)
NCT01552122	PHASE3	WITHDRAWN	Efficacy and Safety of Odanacatib in Postmenopausal Women Previously Treated With Alendronate (MK-0822-050)
NCT01803607	PHASE3	TERMINATED	Efficacy and Safety of Odanacatib in Postmenopausal Women Previously Treated With Oral Bisphosphonate (MK-0822-076)
NCT00112437	PHASE2	COMPLETED	A Study to Examine the Effects of an Experimental Drug on Postmenopausal Osteoporosis (MK-0822-004)
NCT00397683	PHASE2	TERMINATED	A 52-Week Study to Assess the Effects of MK0822 on Knee Osteoarthritis (MK-0822-011)
NCT00399802	PHASE2	COMPLETED	A Study to Examine the Effects of an Experimental Drug on Women With Breast Cancer and Metastatic Bone Disease (MBD)(0822-016)(COMPLETED)
NCT00620113	PHASE2	COMPLETED	Efficacy and Safety of Odanacatib (MK-0822) in Participants With Involutional Osteoporosis (MK-0822-022)
NCT00885170	PHASE2	COMPLETED	A Study to Evaluate the Safety, Tolerability, and Efficacy of Odanacatib (MK-0822) in Postmenopausal Women Previously Treated With a Bisphosphonate (MK-0822-042)
NCT00769418	PHASE1	COMPLETED	Study of Multiple Oral Doses of Odanacatib (MK0822) in Healthy Adults (0822-002)
NCT00770159	PHASE1	COMPLETED	A Study to Test Once-Weekly Doses of Odanacatib (MK0822) on Healthy Adult Females (0822-005)(COMPLETED)
NCT00863525	PHASE1	COMPLETED	A Study to Assess the Effects of a Light Breakfast on the Safety, Tolerability, and Pharmacokinetics of Odanacatib (MK0822)
NCT00863590	PHASE1	COMPLETED	A Single-Dose Study of the Safety, Tolerability, and Pharmacokinetics of Odanacatib (MK0822) in Healthy Volunteers
NCT01068262	PHASE1	COMPLETED	Safety and Tolerability of Odanacatib (0822-059)
NCT01512667	PHASE1	COMPLETED	Pharmacokinetic Assessment of Single-Dose Odanacatib (MK-0822) in Subjects With Severe Renal Insufficiency (MK-0822-067)
NCT01512693	PHASE1	COMPLETED	Assessment of Pharmacokinetics of Single Dose Odanacatib (MK-0822) in Participants With Moderate Hepatic Insufficiency (MK-0822-070)
NCT01630616	PHASE1	TERMINATED	A Study of Odanacatib When Administered to Adolescents and Young Adults Treated With Glucocorticoids (MK-0822-066)

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

12 molecules share ≥1 primary target. Top 12 by shared-target count:

Molecule	Source	Status	Shared targets
BOCEPREVIR	ChEMBL	Phase 4 (approved)	CTSK, CTSS
NIRMATRELVIR	ChEMBL	Phase 4 (approved)	CTSK, CTSS
TELAPREVIR	ChEMBL	Phase 4 (approved)	CTSK, CTSS
ATUZAGINSTAT	ChEMBL	Phase 2	CTSK, CTSS
BALICATIB	ChEMBL	Phase 2	CTSK, CTSS
IBUZATRELVIR	ChEMBL	Phase 2	CTSK, CTSS
RELACATIB	ChEMBL	Phase 2	CTSK, CTSS
SIMEPREVIR	ChEMBL	Phase 4 (approved)	CTSS
VANIPREVIR	ChEMBL	Phase 3	CTSS
K-777	ChEMBL	Phase 2	CTSS
PETESICATIB	ChEMBL	Phase 2	CTSS
Bortezomib	PubChem	Approved	CTSZ