Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DM1EO3G)

• Drug Name: Odanacatib Drug Info
• Synonyms: MK 0822; MK0822; MK-0822A; Odanacatib (USAN)

Indication

Disease Entry	ICD 11	Status	REF
Osteoporosis	FB83.0	Phase 3	[1]

• Cross-matching ID:
  PubChem CID: 10152654
  CAS Number: CAS 603139-19-1
  TTD Drug ID: DM1EO3G
  INTEDE Drug ID: DR1185

Molecule-Related Drug Atlas

Drug(s) Targeting Cathepsin K (CTSK)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
SAR-114137	DMZ1XR5	Pain	MG30-MG3Z	Phase 1	[4]
VEL-0230	DMDSC63	Rheumatoid arthritis	FA20	Phase 1	[5]
PMID27998201-Compound-12	DM8QZNC	Bone cancer	2B5Z	Patented	[6]
PMID27998201-Compound-5	DMVZ0ND	Chronic obstructive pulmonary disease	CA22	Patented	[6]
PMID27998201-Compound-9	DM1JOZN	Rheumatoid arthritis	FA20	Patented	[6]
PMID25399719-Compound-17	DMRXKJZ	N. A.	N. A.	Patented	[7]
PMID27998201-Compound-15	DMOB8LU	Pain	MG30-MG3Z	Patented	[6]
Oxotetrahydro-2-H-furo[3.2-b]pyrrol-4(5-H)-yl derivative 1	DM1SH5R	Pain	MG30-MG3Z	Patented	[6]
PMID27998201-Compound-8	DMZK0SY	N. A.	N. A.	Patented	[6]
PMID27998201-Compound-10	DMVXTIL	Osteoporosis	FB83.0	Patented	[6]

Drug(s) Metabolized By Cytochrome P450 3A4 (CYP3A4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[8]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[9]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[10]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[11]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[12]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[13]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[14]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[15]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[9]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[16]

Drug(s) Metabolized By Cytochrome P450 2C8 (CYP2C8)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[17]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[18]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[18]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[19]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[20]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[21]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[22]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[18]
Mycophenolate mofetil	DMPQAGE	Hepatosplenic T-cell lymphoma		Approved	[23]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[24]

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	[2]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[3]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Substrate	[3]

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] 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.
• [3] Disposition and metabolism of the cathepsin K inhibitor odanacatib in humans. Drug Metab Dispos. 2014 May;42(5):818-27.
• [4] From laboratory to pilot plant: the solid-state process development of a highly potent cathepsin S/K inhibitor. Eur J Pharm Biopharm. 2013 Apr;83(3):436-48.
• [5] Discovery and parallel synthesis of a new class of cathepsin K inhibitors. Bioorg Med Chem Lett. 2001 Nov 19;11(22):2951-4.
• [6] Cathepsin B and L inhibitors: a patent review (2010 - present).Expert Opin Ther Pat. 2017 Jun;27(6):643-656.
• [7] An updated patent review of calpain inhibitors (2012 - 2014).Expert Opin Ther Pat. 2015 Jan;25(1):17-31.
• [8] Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
• [9] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [10] Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
• [11] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [12] Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
• [13] Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
• [14] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [15] The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
• [16] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [17] Roles of cytochromes P450 1A2, 2A6, and 2C8 in 5-fluorouracil formation from tegafur, an anticancer prodrug, in human liver microsomes. Drug Metab Dispos. 2000 Dec;28(12):1457-63.
• [18] Role of cytochrome P450 2C8 in drug metabolism and interactions. Pharmacol Rev. 2016 Jan;68(1):168-241.
• [19] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [20] Differential expression and function of CYP2C isoforms in human intestine and liver. Pharmacogenetics. 2003 Sep;13(9):565-75.
• [21] Analysis of human cytochrome P450 2C8 substrate specificity using a substrate pharmacophore and site-directed mutants. Biochemistry. 2004 Dec 14;43(49):15379-92.
• [22] Interaction of sorafenib and cytochrome P450 isoenzymes in patients with advanced melanoma: a phase I/II pharmacokinetic interaction study. Cancer Chemother Pharmacol. 2011 Nov;68(5):1111-8.
• [23] PharmGKB summary: mycophenolic acid pathway. Pharmacogenet Genomics. 2014 Jan;24(1):73-9.
• [24] Possible involvement of multiple human cytochrome P450 isoforms in the liver metabolism of propofol. Br J Anaesth. 1998 Jun;80(6):788-95.