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

General Information of Drug (ID: DMX0E5B)

• Drug Name: Bimatoprost Drug Info
• Synonyms: Bimatoprost (topical, alopecia)

Indication

Disease Entry	ICD 11	Status	REF
Alopecia	ED70	Approved	[1]
Hypertrichosis of eyelid		Approved	[2]
Ocular hypertension	9C61.01	Approved	[2]
Glaucoma/ocular hypertension	9C61	Phase 3	[3]

• Cross-matching ID:
  PubChem CID: 5311027
  ChEBI ID: CHEBI:51230
  CAS Number: CAS 155206-00-1
  TTD Drug ID: DMX0E5B
  INTEDE Drug ID: DR0213

Molecule-Related Drug Atlas

Drug(s) Targeting Prostaglandin receptor (PTGR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Unoprostone	DMXNR04	Glaucoma/ocular hypertension	9C61	Approved	[6]
Iclaprim	DM7YNV9	Bacterial infection	1A00-1C4Z	Phase 3	[7]
JB991	DMKU6MW	Skin infection	1F28-1G0Z	Phase 2	[8]
Taprostene	DMA4WY5	Thrombosis	DB61-GB90	Discontinued in Phase 3	[9]
ZD-4953	DM5UCHW	Pain	MG30-MG3Z	Discontinued in Phase 2	[10]
TEI-6122	DM3F5E0	Diabetic complication	5A2Y	Discontinued in Phase 2	[11]
YP-009	DMPXLG2	Solid tumour/cancer	2A00-2F9Z	Terminated	[12]
YP-008	DM2N76V	Psoriasis vulgaris	EA90	Terminated	[13]
IP-1200	DMIX7CP	Erectile dysfunction	HA01.1	Investigative	[14]

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	[15]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[16]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[17]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[18]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[19]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[20]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[21]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[22]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[16]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[23]

Drug(s) Metabolized By Cytochrome P450 3A5 (CYP3A5)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[24]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[25]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[26]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[27]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[28]
Sulfasalazine	DMICA9H	Irritable bowel syndrome	DD91.0	Approved	[29]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[30]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[31]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[32]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[27]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Prostaglandin receptor (PTGR)	TT9B4N3	NOUNIPROTAC	Modulator	[4]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[5]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Substrate	[5]

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 1958).
• [2] Bimatoprost FDA Label
• [3] ClinicalTrials.gov (NCT02250651) Safety and Efficacy of Bimatoprost Sustained-Release (SR) in Patients With Open-Angle Glaucoma or Ocular Hypertension. U.S. National Institutes of Health.
• [4] Bimatoprost-induced calcium signaling in human T-cells does not involve prostanoid FP or TP receptors. Curr Eye Res. 2009 Mar;34(3):184-95.
• [5] Product monograph: LUMIGAN RC (Bimatoprost).
• [6] Comparison of the vasoactive effects of the docosanoid unoprostone and selected prostanoids on isolated perfused retinal arterioles. Invest Ophthalmol Vis Sci. 2001 Jun;42(7):1499-504.
• [7] Novel ocular antihypertensive compounds in clinical trials. Clin Ophthalmol. 2011; 5: 667-677.
• [8] US patent application no. 2006,0041,016, Composition and method for the treatment of psoriasis.
• [9] Partial agonism of taprostene at prostanoid IP receptors in vascular preparations from guinea-pig, rat, and mouse. J Cardiovasc Pharmacol. 2004 Jun;43(6):795-807.
• [10] WO patent application no. 2013,1675,82, Methods and pharmaceutical compositions for prevention or treatment of chronic obstructive pulmonary disease.
• [11] The effect of a synthetic 7-thiaprostaglandin E1 derivative, TEI-6122, on monocyte chemoattractant protein-1 induced chemotaxis in THP-1 cells.. Br J Pharmacol. 1995 October; 116(4): 2298-2302.
• [12] YP 009 York Pharma pc preclinical, UK(cancer), R & D Focus Drug News, November 12, 2007
• [13] CA patent application no. 841416, Method of selecting therapeutic indications.
• [14] Clinical pipeline report, company report or official report of Immunologic.
• [15] 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.
• [16] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [17] 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.
• [18] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [19] 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.
• [20] 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.
• [21] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [22] 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.
• [23] 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.
• [24] Drug related genetic polymorphisms affecting adverse reactions to methotrexate, vinblastine, doxorubicin and cisplatin in patients with urothelial cancer. J Urol. 2008 Dec;180(6):2389-95.
• [25] Human prostate CYP3A5: identification of a unique 5'-untranslated sequence and characterization of purified recombinant protein. Biochem Biophys Res Commun. 1999 Jul 14;260(3):676-81.
• [26] Polymorphisms in cytochrome P4503A5 (CYP3A5) may be associated with race and tumor characteristics, but not metabolism and side effects of tamoxifen in breast cancer patients. Cancer Lett. 2005 Jan 10;217(1):61-72.
• [27] Drug Interactions Flockhart Table
• [28] Induction of hepatic CYP2E1 by a subtoxic dose of acetaminophen in rats: increase in dichloromethane metabolism and carboxyhemoglobin elevation. Drug Metab Dispos. 2007 Oct;35(10):1754-8.
• [29] Urinary 6 beta-hydroxycortisol excretion in rheumatoid arthritis. Br J Rheumatol. 1997 Jan;36(1):54-8.
• [30] Clinical pharmacokinetics of imatinib. Clin Pharmacokinet. 2005;44(9):879-94.
• [31] Kinetics and regulation of cytochrome P450-mediated etoposide metabolism. Drug Metab Dispos. 2004 Sep;32(9):993-1000.
• [32] Differential mechanism-based inhibition of CYP3A4 and CYP3A5 by verapamil. Drug Metab Dispos. 2005 May;33(5):664-71.