Details of the Drug

General Information of Drug (ID: DMK7IWL)

Drug Name

Relugolix

Synonyms

737789-87-6; TAK-385; TAK 385; UNII-P76B05O5V6; CHEMBL1800159; TAK-385/TAK385; P76B05O5V6; 1-(4-(1-(2,6-difluorobenzyl)-5-((dimethylamino)methyl)-3-(6-methoxypyridazin-3-yl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl)phenyl)-3-methoxyurea; Relugolix [USAN:INN]; TAK385; Relugolix (JAN/INN); SCHEMBL778416; GTPL5586; DTXSID40224167; MolPort-044-567-649; AOMXMOCNKJTRQP-UHFFFAOYSA-N; EX-A1083; BCP21587; ZINC43206033; BDBM50347982; AKOS027440398; SB16721; DB11853; CS-5917

Indication

Disease Entry	ICD 11	Status	REF
Prostate cancer	2C82.0	Approved	[1]
Endometriosis	GA10	Phase 3	[2]

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 2

Molecular Weight (mw)

623.6

Topological Polar Surface Area (xlogp)

3.2

Rotatable Bond Count (rotbonds)

9

Hydrogen Bond Donor Count (hbonddonor)

2

Hydrogen Bond Acceptor Count (hbondacc)

11

ADMET Property

Absorption AUC: The area under the plot of plasma concentration (AUC) of drug is 574 mcgh/L [3]
Absorption Tmax: The time to maximum plasma concentration (Tmax) is 4.3 h [3]
Bioavailability: The bioavailability of drug is 30-60% [3]
Clearance: The renal clearance of drug is 8 L/h [4]
Elimination: Approximately 81% of an orally administered dose was recovered in the feces, of which 4.2% was unchanged parent drug, while 4.1% of the dose was recovered in the urine, of which 2.2% remained unchanged [4]
Half-life: The concentration or amount of drug in body reduced by one-half in 25 hours [4]
Metabolism: The drug is metabolized via the CYP3A subfamily of P450 enzymes [4]

Chemical Identifiers

Formula: C29H27F2N7O5S
IUPAC Name: 1-[4-[1-[(2,6-difluorophenyl)methyl]-5-[(dimethylamino)methyl]-3-(6-methoxypyridazin-3-yl)-2,4-dioxothieno[2,3-d]pyrimidin-6-yl]phenyl]-3-methoxyurea
Canonical SMILES: CN(C)CC1=C(SC2=C1C(=O)N(C(=O)N2CC3=C(C=CC=C3F)F)C4=NN=C(C=C4)OC)C5=CC=C(C=C5)NC(=O)NOC
InChI: InChI=1S/C29H27F2N7O5S/c1-36(2)14-19-24-26(39)38(22-12-13-23(42-3)34-33-22)29(41)37(15-18-20(30)6-5-7-21(18)31)27(24)44-25(19)16-8-10-17(11-9-16)32-28(40)35-43-4/h5-13H,14-15H2,1-4H3,(H2,32,35,40)
InChIKey: AOMXMOCNKJTRQP-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 10348973
CAS Number: 737789-87-6
DrugBank ID: DB11853
TTD ID: D0F2WP
VARIDT ID: DR00186
ACDINA ID: D01379

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Gonadotropin-releasing hormone receptor (GNRHR)	TT8R70G	GNRHR_HUMAN	Antagonist	[1]

------------------------------------------------------------------------------------

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[5]

------------------------------------------------------------------------------------

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Relugolix (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Ivosidenib	DM8S6T7	Major	Increased risk of prolong QT interval by the combination of Relugolix and Ivosidenib.	Acute myeloid leukaemia [2A60]	[23]
Gilteritinib	DMWQ4MZ	Moderate	Increased risk of prolong QT interval by the combination of Relugolix and Gilteritinib.	Acute myeloid leukaemia [2A60]	[24]
Oliceridine	DM6MDCF	Moderate	Increased risk of prolong QT interval by the combination of Relugolix and Oliceridine.	Acute pain [MG31]	[24]
Levalbuterol	DM5YBO1	Moderate	Increased risk of prolong QT interval by the combination of Relugolix and Levalbuterol.	Asthma [CA23]	[25]
PF-04449913	DMSB068	Moderate	Increased risk of prolong QT interval by the combination of Relugolix and PF-04449913.	Chronic myelomonocytic leukaemia [2A40]	[24]
MK-8228	DMOB58Q	Moderate	Accelerated clearance of Relugolix due to the transporter induction by MK-8228.	Cytomegaloviral disease [1D82]	[26]
Deutetrabenazine	DMUPFLI	Moderate	Increased risk of prolong QT interval by the combination of Relugolix and Deutetrabenazine.	Dystonic disorder [8A02]	[24]
Selpercatinib	DMZR15V	Major	Increased risk of prolong QT interval by the combination of Relugolix and Selpercatinib.	Lung cancer [2C25]	[24]
Siponimod	DM2R86O	Major	Increased risk of ventricular arrhythmias by the combination of Relugolix and Siponimod.	Multiple sclerosis [8A40]	[27]
Ozanimod	DMT6AM2	Major	Increased risk of ventricular arrhythmias by the combination of Relugolix and Ozanimod.	Multiple sclerosis [8A40]	[28]
Entrectinib	DMMPTLH	Moderate	Increased risk of prolong QT interval by the combination of Relugolix and Entrectinib.	Non-small cell lung cancer [2C25]	[24]
Rucaparib	DM9PVX8	Moderate	Increased risk of prolong QT interval by the combination of Relugolix and Rucaparib.	Ovarian cancer [2C73]	[24]
Triclabendazole	DMPWGBR	Moderate	Increased risk of prolong QT interval by the combination of Relugolix and Triclabendazole.	Parasitic worm infestation [1F90]	[24]
Macimorelin	DMQYJIR	Major	Increased risk of prolong QT interval by the combination of Relugolix and Macimorelin.	Pituitary gland disorder [5A60-5A61]	[29]
Lefamulin	DME6G97	Major	Increased risk of prolong QT interval by the combination of Relugolix and Lefamulin.	Pneumonia [CA40]	[30]
Fostamatinib	DM6AUHV	Major	Decreased clearance of Relugolix due to the transporter inhibition by Fostamatinib.	Thrombocytopenia [3B64]	[26]
Elagolix	DMB2C0E	Major	Decreased clearance of Relugolix due to the transporter inhibition by Elagolix.	Uterine fibroid [2E86]	[26]
-----------


⏷ Show the Full List of 17 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Mannitol	E00103	6251	Diluent; Flavoring agent; Lyophilization aid; Plasticizing agent; Tonicity agent
Hydroxypropyl cellulose	E00632	Not Available	Binding agent; Coating agent; Emulsifying agent; Film/Membrane-forming agent; Modified-release agent; Suspending agent; Viscosity-controlling agent
Hypromellose	E00634	Not Available	Coating agent
Magnesium stearate	E00208	11177	lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Haematite red	E00236	14833	Colorant
--------------------


⏷ Show the Full List of 6 Pharmaceutical Excipients of This Drug

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Relugolix 120 mg tablet	120 mg	Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
2	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
3	Hiemke C: [Paroxetine: pharmacokinetics and pharmacodynamics]. Fortschr Neurol Psychiatr. 1994 Sep;62 Suppl 1:2-8.
4	FDA Approved Drug Products: Orgovyx (relugolix) tablets for oral use
5	KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 2017 Jan 4;45(D1):D353-D361. (dg:DG01665)
6	Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
7	MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
8	Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
9	Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
10	Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
11	Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
12	Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia. Ther Drug Monit. 2011 Apr;33(2):244-50.
13	Use of cognitive behavior therapy for functional hypothalamic amenorrhea. Ann N Y Acad Sci. 2006 Dec;1092:114-29.
14	Age attenuates testosterone secretion driven by amplitude-varying pulses of recombinant human luteinizing hormone during acute gonadotrope inhibiti... J Clin Endocrinol Metab. 2007 Sep;92(9):3626-32.
15	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
16	Regulation of GnRH I receptor gene expression by the GnRH agonist triptorelin, estradiol, and progesterone in the gonadotroph-derived cell line alphaT3-1. Endocrine. 2006 Aug;30(1):139-44.
17	Clinical pipeline report, company report or official report of Takeda (2009).
18	Reversible downregulation of endocrine and germinative testicular function (hormonal castration) in the dog with the GnRH-agonist azagly-nafarelin ... Theriogenology. 2009 Apr 15;71(7):1037-45.
19	Gonadotropin releasing hormone analogs induce apoptosis by extrinsic pathway involving p53 phosphorylation in primary cell cultures of human prostatic adenocarcinomas. Prostate. 2009 Jul 1;69(10):1025-33.
20	2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
21	Iterative approach to the discovery of novel degarelix analogues: substitutions at positions 3, 7, and 8. Part II. J Med Chem. 2005 Jul 28;48(15):4851-60.
22	Stability of cytotoxic luteinizing hormone-releasing hormone conjugate (AN-152) containing doxorubicin 14-O-hemiglutarate in mouse and human serum in vitro: implications for the design of preclinicalstudies. Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):829-34.
23	Product Information. Tibsovo (ivosidenib). Agios Pharmaceuticals, Cambridge, MA.
24	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
25	Product Information. Arcapta Neohaler (indacaterol). Novartis Pharmaceuticals, East Hanover, NJ.
26	Product Information. Orgovyx (relugolix). Myovant Sciences, Inc., Brisbane, CA.
27	Cerner Multum, Inc. "Australian Product Information.".
28	Product Information. Zeposia (ozanimod). Celgene Corporation, Summit, NJ.
29	Product Information. Macrilen (macimorelin). Aeterna Zentaris, Charleston, SC.
30	Product Information. Xenleta (lefamulin). Nabriva Therapeutics US, Inc., King of Prussia, PA.