生物活性

• 描述Riociguat is a potent sGC (soluble guanylate cyclase) stimulator with improved DMPK profile, used for the treatment of pulmonary hypertension^[7]. It directly stimulates sGC and sensitises it to its physiological stimulator, nitric oxide^[8]. It achieved threefold stimulation of cGMP formation in a recombinant sGC-overexpressing cell line with minimal effective concentration of 30nM^[7]. Oral administration of BAY 63-2521 at 10 mg/kg/day partially reversed the pulmonary arterial hypertension induced by monocrotaline in rats or in chronic treatment of hypoxic mice. The reversion of the right heart hypertrophy and the structural remodelling of the lung vasculature could also be observed^[8].

• 动物研究
  剂量	Rat； 0.1 mg/kg[3] (i.v.); 10 mg/kg[4] (p.o.) Mice: 30 mg/kg[5] (p.o.)
  给药途径	i.v., p.o.
  动物药代数据	Animal Rats[6] F 35% - 65% CL 1.3 L/kg·h Vdss 1.2 L/kg

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT01347216	-	-	Recruiting	June 2020	Belgium ... more >> Dept. of Pneumology, University Recruiting Leuven, Belgium Contact: Marion Delcroix, MD, PhD          Principal Investigator: Marion Delcroix, MD, PhD          Germany DRK-Klinikum Köpenick Recruiting Berlin, Germany Contact: Christian Opitz, MD, PhD          Principal Investigator: Christian Opitz, MD, PhD          Lung Centre, University of Giessen Recruiting Giessen, Germany Contact: Ardeschir Ghofrani, MD, PhD          Principal Investigator: Ardeschir Ghofrani, MD          Sub-Investigator: Melanie Thamm, MD          Department of Pulmology; Hannover Medical School Recruiting Hannover, Germany Contact: Marius M Hoeper          Principal Investigator: Marius M Hoeper, MD, PhD          Sub-Investigator: Karen Olsson, MD          German Heart Centre Recruiting Munich, Germany Contact: Harald Kaemmerer, MD,. PhD          Principal Investigator: Harald Kaemmerer, MD, PhD          Ireland Mater Misericordiae Recruiting Dublin, Ireland Contact: Sean Gaine, MD, PhD          Principal Investigator: Sean Gaine, MD, PhD          Italy Department of Cardiovascular and Respiratory Sciences, University La Sapienza Recruiting Rome, Italy Contact: Dario Vizza, MD, PhD          Principal Investigator: Dario Vizza, MD, PhD          Switzerland Dept. for Rheumatology, University Hospital Recruiting Zurich, Switzerland Contact: Oliver Distler, MD, PhD          Principal Investigator: Oliver Distler, MD, PhD Collapse <<
  NCT01266265	-	-	Completed	-	-
  NCT02565030	-	-	Active, not recruiting	October 2021	United Kingdom ... more >> Sheffield Teaching Hospitals NHS Foundation Trust Sheffield, South Yorkshire, United Kingdom, S10 2JF Collapse <<

• 更多
• 参考文献

• [1] Mittendorf J, Weigand S, et al. Discovery of riociguat (BAY 63-2521): a potent, oral stimulator of soluble guanylate cyclase for the treatment of pulmonary hypertension. ChemMedChem. 2009 May;4(5):853-65.

  [2] Schermuly RT, Stasch JP, et al. Expression and function of soluble guanylate cyclase in pulmonary arterial hypertension. Eur Respir J. 2008 Oct;32(4):881-91.

  [3] Chamorro V, Morales-Cano D, et al. Riociguat versus sildenafil on hypoxic pulmonary vasoconstriction and ventilation/perfusion matching. PLoS One. 2018 Jan 24;13(1):e0191239.

  [4] Lang M, Kojonazarov B, et al. The soluble guanylate cyclase stimulator riociguat ameliorates pulmonary hypertension induced by hypoxia and SU5416 in rats. PLoS One. 2012;7(8):e43433.

  [5] Rai N, Veeroju S, et al. Effect of Riociguat and Sildenafil on Right Heart Remodeling and Function in Pressure Overload Induced Model of Pulmonary Arterial Banding. Biomed Res Int. 2018 Jan 3;2018:3293584.

  [6] BAY 63-2521

  [7] Mittendorf J, Weigand S, Alonso-Alija C, Bischoff E, Feurer A, Gerisch M, Kern A, Knorr A, Lang D, Muenter K, Radtke M, Schirok H, Schlemmer KH, Stahl E, Straub A, Wunder F, Stasch JP. Discovery of riociguat (BAY 63-2521): a potent, oral stimulator of soluble guanylate cyclase for the treatment of pulmonary hypertension. ChemMedChem. 2009 May;4(5):853-65. doi: 10.1002/cmdc.200900014. PMID: 19263460.

  [8] Schermuly RT, Stasch JP, Pullamsetti SS, Middendorff R, Müller D, Schlüter KD, Dingendorf A, Hackemack S, Kolosionek E, Kaulen C, Dumitrascu R, Weissmann N, Mittendorf J, Klepetko W, Seeger W, Ghofrani HA, Grimminger F. Expression and function of soluble guanylate cyclase in pulmonary arterial hypertension. Eur Respir J. 2008 Oct;32(4):881-91. doi: 10.1183/09031936.00114407. Epub 2008 Jun 11. PMID: 18550612.

• 更多

• Collapse