Macitentan

Research use only, not for human use.

Macitentan is an orally active, non-peptide, dual ETA/ETB (endothelin) receptor antagonist with IC50 of 0.5 nM/391 nM.

Macitentan is an orally active, non-peptide, dual ETA/ETB (endothelin) receptor antagonist with IC50 of 0.5 nM/391 nM.(In Vitro):Tube formation ability is restored when microvascular endothelial cells are preincubated with BOS or macitentan (ACT-064992), also reducing the expression of mesenchymal markers and restoring CD31 expression and the imbalance between VEGF-A and VEGF-A165b. 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. 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. (In Vivo):Macitentan (ACT-064992; 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 proteinproduction in type 2 diabetes in type 2 diabetes. 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.

Tube formation ability is restored when microvascular endothelial cells are preincubated with BOS or macitentan (ACT-064992), also reducing the expression of mesenchymal markers and restoring CD31 expression and the imbalance between VEGF-A and VEGF-A165b. 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. 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.

Macitentan (ACT-064992; 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. 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.

ACT-064992

GPCR/G Protein

Endothelin Receptor

ET-A| ET-B

Cardiovascular Disease

——

441798-33-0

588.27

C19H20Br2N6O4S

>98% (HPLC)

DMSO: 100 mg/mL (169.98 mM)

O=S(NCCC)(NC1=NC=NC(OCCOC2=NC=C(Br)C=N2)=C1C3=CC=C(Br)C=C3)=O

N-[5-(4-bromophenyl)-6-{2-[(5-bromopyrimidin-2-yl)oxy]ethoxy}pyrimidin-4-yl]-N'- propylsulfamide

(-20℃)

With Ice Pack

≥ 2 years