"目录号: HY-14184
GPCR/G Protein-
Macitentan 是一种可口服的非肽类的ETA和ETB receptor的双重拮抗剂，能有有效治疗特发性肺纤维化和肺动脉高压症状。
Endothelin Receptor
相关产品
Atrasentan hydrochloride-BQ-788 sodium salt-Bosentan-Ambrisentan-Avosentan-BQ-123-ACT-132577-Sitaxsentan sodium-Sulfisoxazole-Zibotentan-Endothelin 1 swine, human-Aminaftone-Macitentan n-butyl analogue-PD-159020-Ro 46-2005-
生物活性
Description
Macitentan is an orally active, non-peptide dual endothelinETAandETB receptorantagonist for the potential treatment of idiopathic pulmonary fibrosis (IPF) and pulmonary arterial hypertension (PAH).
In Vitro
Tube formation ability is restored when microvascular endothelial cells are preincubated with BOS or macitentan, also reducing the expression of mesenchymal markers and restoring CD31 expression and the imbalance between VEGF-A and VEGF-A165b[1]. Macitentan inhibits OATP1B1-mediated uptake of atorvastatin and OATP1B3-mediated uptake of estrone-3-sulfate with IC50?±?SE values of 6.3?±?0.7 and 11.8?±?5.0?μM, respectively[3]. Treatment with macitentan or with ACT-132577 does not lead to intracellular accumulation of R123 in HeyA8-MDR, showing that these compounds are not P-gp inhibitors[4].
In Vivo
Macitentan (25 mg/kg/day, p.o.) prevents increased production of vasoactive and fibrogenic factors, NF-κB activation, structural and functional changes, and increases extracellular matrix protein production in type 2 diabetes in type 2 diabetes[2]. Macitentan (10 mg/kg, p.o.) coupled with once-per-week 5 mg/kg taxol, significantly reduces the weight (size) of HeyA8-MDR tumors in mice. Combination therapy with macitentan (10 or 50 mg/kg, but not 5 mg/kg) and taxol or macitentan (10 mg/kg) and cisplatinum significantly reduces the number of proliferating Ki-67-positive cells[4].
Clinical Trial
NCT00660179
Actelion
Pulmonary Arterial Hypertension
May 2008
Phase 3
NCT00903331
Actelion
Idiopathic Pulmonary Fibrosis
May 2009
Phase 2
NCT00660179
Actelion
Pulmonary Arterial Hypertension
May 2008
Phase 3
NCT00903331
Actelion
Idiopathic Pulmonary Fibrosis
May 2009
Phase 2
NCT02651272
Boston University-Actelion
Pulmonary Hypertension-Sickle Cell Disease
July 2015
Phase 1
NCT01841762
Actelion
Pulmonary Arterial Hypertension
April 2013
Phase 3
NCT02254954
Actelion
Glioblastoma
October 2014
Phase 1
NCT01739400
Actelion
Pulmonary Arterial Hypertension
September 1, 2013
Phase 3
NCT02310672
Actelion
Pulmonary Arterial Hypertension
June 1, 2015
Phase 4
NCT01847014
Actelion
Pulmonary Arterial Hypertension
September 2013
Phase 3
NCT02060721
Actelion
Chronic Thromboembolic Pulmonary Hypertension
February 9, 2015
Phase 2
NCT02081690
Actelion
Pulmonary Arterial Hypertension
March 2014
Phase 3
NCT01743001
Actelion
Pulmonary Arterial Hypertension
May 2013
Phase 3
NCT02932410
Actelion
Pulmonary Arterial Hypertension
July 15, 2017
Phase 3
NCT02021292
Actelion
Chronic Thromboembolic Pulmonary Hypertension
August 2014
Phase 2
NCT01474122
Actelion
Digital Ulcers
December 2011
Phase 3
NCT01474109
Actelion
Systemic Sclerosis-Ulcers
December 2011
Phase 3
NCT02893176
University of California, Los Angeles
Lung Transplant Rejection
September 2016
Phase 4
NCT01346930
Actelion
Idiopathic Pulmonary Fibrosis
July 2011
Phase 2
NCT02382016
Actelion
Portopulmonary Hypertension
June 1, 2015
Phase 4
NCT02126943
Actelion
Pulmonary Arterial Hypertension
April 1, 2014
NCT03215966
Actelion
Healthy Subjects
August 3, 2017
Phase 1
NCT00667823
Actelion
Pulmonary Arterial Hypertension
October 1, 2008
Phase 3
NCT02112487
Actelion
Pulmonary Arterial Hypertension
June 1, 2014
Phase 3
NCT02554903
Actelion
Pulmonary Hypertension
December 2015
Phase 2
NCT02070991
Actelion
Pulmonary Hypertension
July 2014
Phase 2
NCT02050802
Actelion
Healthy
August 2011
Phase 1
NCT03153137
Actelion
Congenital Heart Disease
August 15, 2017
Phase 3
NCT02968901
Actelion
Pulmonary Arterial Hypertension
September 2015
Phase 4
NCT03153111
Actelion
Heart Failure With Preserved Ejection Fraction
July 31, 2017
Phase 2
NCT02558231
Actelion
Pulmonary Arterial Hypertension
May 2016
Phase 3
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References
[1].Corallo C, et al. Bosentan and macitentan prevent the endothelial-to-mesenchymal transition (EndoMT) in systemic sclerosis: in vitro study. Arthritis Res Ther. 2016 Oct 6;18(1):228.
[2].Sen S, et al. Renal, retinal and cardiac changes in type 2 diabetes are attenuated by macitentan, a dual endothelin receptor antagonist. Life Sci. 2012 Apr 13.
[3].Bruderer S, et al. Effect of cyclosporine and rifampin on the pharmacokinetics of macitentan, a tissue-targeting dual endothelin receptor antagonist. AAPS J. 2012 Mar;14(1):68-78.
[4].Kim SJ, et al. Antivascular therapy for multidrug-resistant ovarian tumors by macitentan, a dual endothelin receptor antagonist.Transl Oncol. 2012 Feb;5(1):39-47.