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Related Concept Videos

Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists01:23

Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists

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Prostacyclin receptor agonists are a class of therapeutic agents integral to managing pulmonary arterial hypertension (PAH). These drugs operate by mimicking the action of prostaglandin I2, or PGI2, a naturally occurring compound in the body.
These agonists bind to the IPR receptor situated on the plasma membrane of the pulmonary artery smooth muscle cells. This binding triggers a cascade of reactions known as the GS-AC-cAMP-PKA pathway. This pathway results in the relaxation of smooth muscle...
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Endothelins (ETs) are potent vasoactive peptides critical in the human body's various physiological and pathological processes. One of the most promising therapeutic strategies for treating pulmonary arterial hypertension (PAH) involves counteracting the effects of these endothelins using a class of drugs known as endothelin receptor antagonists.
ETs are synthesized through a complex sequence of enzymatic steps, primarily involving an enzyme referred to as endothelin-converting enzyme...
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Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers01:26

Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers

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Receptor tyrosine kinase inhibitors (TKIs) and calcium channel blockers (CCBs) are two critical categories of drugs employed in the treatment of pulmonary artery hypertension (PAH). PAH is a disease that causes high blood pressure in the pulmonary arteries, resulting in chest pain, fatigue, and shortness of breath.
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
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Treatment for Pulmonary Arterial Hypertension: Phosphodiesterase Inhibitors01:28

Treatment for Pulmonary Arterial Hypertension: Phosphodiesterase Inhibitors

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Phosphodiesterase 5 (PDE5) inhibitors are potent enzymes that function to hydrolyze cyclic nucleotides to their corresponding 5' monophosphates. Their unique biochemical properties have been applied in treating Pulmonary Arterial Hypertension (PAH).
Among the PDE5 inhibitors, sildenafil (Revatio) stands out as a competitive and selective inhibitor. It operates by elevating cellular levels of cGMP and augmenting signaling through the cGMP-PKG pathway, promoting vasodilation. Upon oral...
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Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
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Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
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Sotatercept: A First-In-Class Activin Signaling Inhibitor for Pulmonary Arterial Hypertension.

Aimon C Miranda1, Cyrille K Cornelio1, Bao Anh C Tran1

  • 1Department of Pharmacotherapeutics and Clinical Research, Taneja College of Pharmacy, University of South Florida Health, Tampa, FL, USA.

The Journal of Pharmacy Technology : Jpt : Official Publication of the Association of Pharmacy Technicians
|February 25, 2025
PubMed
Summary

Sotatercept shows promise as an add-on therapy for pulmonary arterial hypertension (PAH) patients, improving exercise capacity and key clinical markers. Further research is needed for treatment-naïve and severe PAH cases.

Keywords:
activin signaling inhibitorpulmonary arterial hypertensionsotaterceptsotatercept-csrktransforming growth factor-beta

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Area of Science:

  • Cardiovascular Medicine
  • Pulmonary Hypertension Research
  • Pharmacology

Background:

  • Pulmonary arterial hypertension (PAH) is a progressive disease characterized by high blood pressure in the pulmonary arteries.
  • Current PAH treatments aim to alleviate symptoms and slow disease progression, but often fall short of addressing underlying pathophysiology.
  • Sotatercept represents a novel therapeutic approach targeting the underlying molecular pathways of PAH.

Purpose of the Study:

  • To comprehensively review the characteristics, efficacy, safety, and clinical relevance of sotatercept in treating pulmonary arterial hypertension (PAH).
  • To synthesize data from Phase II and III clinical trials to evaluate sotatercept's impact on PAH patients.

Main Methods:

  • Systematic literature search of Embase, MEDLINE, medRxiv, Cochrane Library, and ClinicalTrials.gov up to October 31, 2024.
  • Inclusion of Phase II-III clinical trials investigating sotatercept for PAH; exclusion of animal studies and Phase I trials.
  • Data extraction and synthesis focusing on efficacy endpoints, safety profiles, and clinical relevance.

Main Results:

  • Sotatercept, as an add-on therapy for WHO Group 1 PAH (functional class II-III), significantly improved 6-minute walk distance in Phase II-III trials.
  • Pooled analysis of PULSAR and STELLAR trials demonstrated improvements in pulmonary vascular resistance and NT-proBNP levels.
  • Further analyses indicated preserved treatment effects at 1 year and improvements in right ventricular structure and function, irrespective of BMPR2 genetic variant status.

Conclusions:

  • Sotatercept is a promising and viable add-on therapy for patients with WHO Group 1 PAH, functional class II-III.
  • The drug demonstrates efficacy in improving key clinical parameters and right ventricular function.
  • Long-term outcomes in treatment-naïve patients and those with severe PAH require further investigation.