MACITENTAN

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H20Br2N6O4S
Molecular Weight	588.273
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCCNS(=O)(=O)NC1=C(C2=CC=C(Br)C=C2)C(OCCOC3=NC=C(Br)C=N3)=NC=N1

InChI

InChIKey=JGCMEBMXRHSZKX-UHFFFAOYSA-N

InChI=1S/C19H20Br2N6O4S/c1-2-7-26-32(28,29)27-17-16(13-3-5-14(20)6-4-13)18(25-12-24-17)30-8-9-31-19-22-10-15(21)11-23-19/h3-6,10-12,26H,2,7-9H2,1H3,(H,24,25,27)

HIDE SMILES / InChI

Molecular Formula	C19H20Br2N6O4S
Molecular Weight	588.273
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/204410s008lbl.pdf
Curator's Comment: description was created based on several sources, including http://www.ncbi.nlm.nih.gov/pubmed/?term=26111581

Macitentan is an orally active, dual endothelin receptor antagonist with tissue targeting properties. Macitentan inhibits both ETA and ETB receptors and prevents them from binding to ET-1. Macitentan displays high affinity and sustained occupancy of the ET receptors in human pulmonary arterial smooth muscle cells. One of the metabolites of macitentan is also pharmacologically active at the ET receptors and is estimated to be about 20% as potent as the parent drug in vitro. Macitentan is approved in the EU (as monotherapy or combination therapy) for the long-term treatment of pulmonary arterial hypertension (PAH) in adults of WHO functional class II or III, and in the USA for the treatment of PAH (WHO group I) to delay disease progression and reduce hospitalization for PAH.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Endothelin-1 receptor 7 Target ID: P25101\|\|\|Q16433 Gene ID: 1909.0 Gene Symbol: EDNRA Target Organism: Homo sapiens (Human) Sources: http://www.ncbi.nlm.nih.gov/pubmed/?term=26111581	Antagonist 2849		0.5 nM [IC50]
Endothelin B receptor 2 Target ID: P24530\|\|\|Q8NHM8 Gene ID: 1910.0 Gene Symbol: EDNRB Target Organism: Homo sapiens (Human) Sources: http://www.ncbi.nlm.nih.gov/pubmed/?term=22862294	Antagonist 2849		391.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pulmonary arterial hypertension 36 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/204410s008lbl.pdf	Primary		Approved 8583	OPSUMIT Approved Use Indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) to delay disease progression. Disease progression included: death, initiation of intravenous (IV) or subcutaneous prostanoids, or clinical worsening of PAH (decreased 6-minute walk distance, worsened PAH symptoms and need for additional PAH treatment). OPSUMIT also reduced hospitalization for PAH. Launch Date 2013

C_max

Value	Dose	Co-administered	Analyte	Population
227 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/23568224	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		MACITENTAN blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
178 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/23568224	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		APROCITENTAN blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
5759 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/23568224	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		MACITENTAN blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
19749 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/23568224	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		APROCITENTAN blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
14.1 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/23568224	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		MACITENTAN blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
46.7 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/23568224	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		APROCITENTAN blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
600 mg single, oral Highest studied dose Dose: 600 mg Route: oral Route: single Dose: 600 mg Sources: https://pubmed.ncbi.nlm.nih.gov/21541781	healthy, 19– 49 years Health Status: healthy Age Group: 19– 49 years Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/21541781	DLT: Headache, Nausea... Dose limiting toxicities: Headache (moderate, 5 patients) Nausea (2 patients) Vomiting (2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/21541781
300 mg single, oral MTD Dose: 300 mg Route: oral Route: single Dose: 300 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204410Orig1s000MedR.pdf https://pubmed.ncbi.nlm.nih.gov/21541781	healthy, 19– 49 years Health Status: healthy Age Group: 19– 49 years Sex: M Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204410Orig1s000MedR.pdf https://pubmed.ncbi.nlm.nih.gov/21541781	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204410Orig1s000MedR.pdf https://pubmed.ncbi.nlm.nih.gov/21541781
10 mg 1 times / day steady, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204410s000lbl.pdf	pregnant, adult Health Status: pregnant Age Group: adult Sex: F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204410s000lbl.pdf	Other AEs: Fetal damage... Other AEs: Fetal damage Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204410s000lbl.pdf

AEs

AE	Significance	Dose	Population
Nausea	2 patients DLT	600 mg single, oral Highest studied dose Dose: 600 mg Route: oral Route: single Dose: 600 mg Sources: https://pubmed.ncbi.nlm.nih.gov/21541781	healthy, 19– 49 years Health Status: healthy Age Group: 19– 49 years Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/21541781
Vomiting	2 patients DLT	600 mg single, oral Highest studied dose Dose: 600 mg Route: oral Route: single Dose: 600 mg Sources: https://pubmed.ncbi.nlm.nih.gov/21541781	healthy, 19– 49 years Health Status: healthy Age Group: 19– 49 years Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/21541781
Headache	moderate, 5 patients DLT	600 mg single, oral Highest studied dose Dose: 600 mg Route: oral Route: single Dose: 600 mg Sources: https://pubmed.ncbi.nlm.nih.gov/21541781	healthy, 19– 49 years Health Status: healthy Age Group: 19– 49 years Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/21541781
Fetal damage		10 mg 1 times / day steady, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204410s000lbl.pdf	pregnant, adult Health Status: pregnant Age Group: adult Sex: F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204410s000lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946 inhibitor 2252 inducer 1087	inhibitor 2438 inducer 440 substrate 1193	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
BSEP 550 NTCP 39 OATP1B1 1079 OATP1B3 961 P-gp 1741 CYP1A2 2153 CYP2A6 879 CYP2B6 926 CYP2C19 2057 CYP2E1 1060 CYP2C8 1057 BCRP 910 MATE1 415 MATE2 267 OAT1 725 OAT3 747 OCT1 620 OCT3 159	P-gp 2052 CYP2C19 1119 OATP1B1 503 OATP1B3 435 BCRP 697 BSEP 63 CYP2C8 810 MATE1 182 MATE2 98 NTCP 22 OAT1 395 OAT3 391 OCT1 393 OCT3 92	CYP1A2 832

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP3A4 2633	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204410Orig1s000ClinPharmR.pdf Page: 63, 64	likely
OATP1B3 970	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204410Orig1s000PharmR.pdf Page: 55.0	no [IC50 14 uM]
OATP1B1 1095	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204410Orig1s000PharmR.pdf Page: 55.0	no [IC50 6.9 uM]
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204410Orig1s000ClinPharmR.pdf Page: 63.0	no
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204410Orig1s000ClinPharmR.pdf Page: 63.0	no
CYP2A6 911	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204410Orig1s000ClinPharmR.pdf Page: 63.0	no
CYP2B6 1160	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204410Orig1s000ClinPharmR.pdf Page: 63.0	no
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204410Orig1s000ClinPharmR.pdf Page: 63.0	no
CYP2C9 2497	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204410Orig1s000ClinPharmR.pdf Page: 63.0	no
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204410Orig1s000ClinPharmR.pdf Page: 63.0	no
CYP2E1 1146	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204410Orig1s000ClinPharmR.pdf Page: 63.0	no
MATE1 416	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/204410s017lbl.pdf Page: 10.0	no
MATE2 267	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/204410s017lbl.pdf Page: 10.0	no
OAT1 730	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/204410s017lbl.pdf Page: 10.0	no
OAT3 749	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/204410s017lbl.pdf Page: 10.0	no
OCT1 656	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/204410s017lbl.pdf Page: 10.0	no
OCT3 161	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/204410s017lbl.pdf Page: 10.0	no
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204410Orig1s000PharmR.pdf Page: 54.0	no
BCRP 985	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/204410s017lbl.pdf Page: 10.0	no	no (co-administration study) Comment: macitentan did not affect the pharmacokinetics of concomitant use of a BCRP substrate drug riociguat or rosuvastatin Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/204410s017lbl.pdf Page: 10.0
BSEP 554	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204410Orig1s000PharmR.pdf Page: 55.0	unlikely [IC50 18 uM]
NTCP 40	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204410Orig1s000PharmR.pdf Page: 55.0	unlikely [IC50 19 uM]
PXR 51	activator 342 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204410Orig1s000ClinPharmR.pdf Page: 63.0	yes [EC50 1.1 uM]
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204410Orig1s000ClinPharmR.pdf Page: 63.0	yes [IC50 21 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204410Orig1s000ClinPharmR.pdf Page: 63.0	yes [IC50 24 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204410Orig1s000ClinPharmR.pdf Page: 63.0	yes [IC50 5.6 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP3A4 1946	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204410Orig1s000ClinPharmR.pdf Page: 52, 61, 63, 65	major	yes (co-administration study) Comment: ketoconazole increased macitentan Cmax by 1.3-fold and AUC by 2.3-fold; rifampin decreased macitentan expsoure by 80% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204410Orig1s000ClinPharmR.pdf Page: 52, 61, 63, 65
CYP2C19 1119	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204410Orig1s000ClinPharmR.pdf Page: 51, 52, 61, 63, 64	minor
CYP2C8 810	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/204410s017lbl.pdf Page: 10.0	minor
CYP2C9 1193	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/204410s017lbl.pdf Page: 10.0	minor	no (co-administration study) Comment: warfarin had no significant impact on the exposure to macitentan Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/204410s017lbl.pdf Page: 10.0
BCRP 697	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/204410s017lbl.pdf Page: 10.0	no
BSEP 63	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/204410s017lbl.pdf Page: 10.0	no
MATE1 182	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/204410s017lbl.pdf Page: 10.0	no
MATE2 98	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/204410s017lbl.pdf Page: 10.0	no
NTCP 22	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/204410s017lbl.pdf Page: 10.0	no
OAT1 395	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/204410s017lbl.pdf Page: 10.0	no
OAT3 391	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/204410s017lbl.pdf Page: 10.0	no
OCT1 393	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/204410s017lbl.pdf Page: 10.0	no
OCT3 92	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/204410s017lbl.pdf Page: 10.0	no
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204410Orig1s000PharmR.pdf Page: 7.0	no
OATP1B1 503	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204410Orig1s000ClinPharmR.pdf Page: 52, 64	no	no (co-administration study) Comment: cyclosporine-A had no significant impact on the exposure to macitentan Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204410Orig1s000ClinPharmR.pdf Page: 52, 64
OATP1B3 435	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204410Orig1s000ClinPharmR.pdf Page: 52, 64	no	no (co-administration study) Comment: cyclosporine-A had no significant impact on the exposure to macitentan Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204410Orig1s000ClinPharmR.pdf Page: 52, 64

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204410Orig1s000PharmR.pdf Page: 28.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:76607	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:76607
MolPort	MolPort-023-299-418	https://www.molport.com/shop/molecule-link/MolPort-023-299-418
Selleck Chemicals	macitentan	http://www.selleckchem.com/products/macitentan.html
ZINC	ZINC000043202140	http://zinc15.docking.org/substances/ZINC000043202140

PubMed

Title	Date	PubMed
Endothelin-1 receptor antagonists in fetal development and pulmonary arterial hypertension.	2015-08-15	26111581
The discovery of N-[5-(4-bromophenyl)-6-[2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy]-4-pyrimidinyl]-N'-propylsulfamide (Macitentan), an orally active, potent dual endothelin receptor antagonist.	2012-09-13	22862294

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dosage is 10 mg once daily for oral administration.

Route of Administration: Oral

In Vitro Use Guide

Unknown

Substance Class	Chemical Created by `admin` on `Wed Apr 02 09:29:32 GMT 2025` Edited by `admin` on `Wed Apr 02 09:29:32 GMT 2025`
Record UNII	Z9K9Y9WMVL
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

MACITENTAN

Official Name

English

OPSUMIT

Preferred Name

English

MACITENTAN [VANDF]

Common Name

English

MACITENTAN [JAN]

Common Name

English

MACITENTAN [ORANGE BOOK]

Common Name

English

MACITENTAN [USAN]

Common Name

English

Macitentan [WHO-DD]

Common Name

English

ACT 064992

Code

English

MACITENTAN [MI]

Common Name

English

N-(5-(4-BROMOPHENYL)-6-(2-((5-BROMOPYRIMIDIN-2-YL)OXY)ETHOXY)PYRIMIDIN-4-YL)-N'-PROPYLSULFAMIDE

Systematic Name

English

N-(5-(4-BROMOPHENYL)-6-(2-((5-BROMOPYRIMIDIN-2-YL)OXI)ETHOXY)PYRIMIDIN-4-YL)-N'-PROPYLSULFURIC DIAMIDE

Common Name

English

ACT-064992

Code

English

SULFAMIDE, N-(5-(4-BROMOPHENYL)-6-(2-((5-BROMO-2-PYRIMIDINYL)OXY)ETHOXY)-4-PYRIMIDINYL)-N'-PROPYL-

Systematic Name

English

macitentan [INN]

Common Name

English

OPSYNVI COMPONENT MACITENTAN

Brand Name

English

Classification Tree Code System Code

WHO-ATC

C02KX04