[PP.02.17] Successful Completion of a Phase I, Randomized, Double-Blind, Placebo Controlled, Single Ascending Dose Trial for the First in Class Angiotensin At2-Receptor Agonist Compound 21

Steckelings, Ulrike Muscha; Lindblad, L.; Leisvuori, Anna; Lovró, Zsófia; Vainio, Paula; Graens, J.; Dahlöf, Björn; Jansson, Paul; Unger, Thomas; Wiksten, Anna; Korhonen, Pasi K.; Scheinin, Mika

doi:10.1097/01.hjh.0000523257.57873.95

Cited by 13 publications

(6 citation statements)

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“…Collectively, these studies demonstrate consideration of many of the STAIR guidelines criteria for preclinical stroke studies [ 11 ] arguably placing this potential novel therapeutic, C21, ahead of other strategies to target the counter regulatory axis of the RAS in the setting of stroke. Furthermore, recently C21 was shown to be safe and well-tolerated when administered orally in healthy adult male volunteers [ 282 ] and further ongoing trials with C21 in Raynaud's phenomenon ( ClinicalTrials.gov Identifier: NCT04388176 ), idiopathic pulmonary fibrosis ( ClinicalTrials.gov Identifier: NCT04533022 ) and COVID-19 ( ClinicalTrials.gov Identifier: NCT04452435 ) will provide further evidence on its safety in human subjects.…”

Section: At 2 R and Strokementioning

confidence: 99%

The counter regulatory axis of the renin angiotensin system in the brain and ischaemic stroke: Insight from preclinical stroke studies and therapeutic potential

McFall

Nicklin

Work

2020

Cellular Signalling

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Stroke is the 2nd leading cause of death worldwide and the leading cause of physical disability and cognitive issues. Although we have made progress in certain aspects of stroke treatment, the consequences remain substantial and new treatments are needed. Hypertension has long been recognised as a major risk factor for stroke, both haemorrhagic and ischaemic. The renin angiotensin system (RAS) plays a key role in blood pressure regulation and this, plus local expression and signalling of RAS in the brain, both support the potential for targeting this axis therapeutically in the setting of stroke. While historically, focus has been on suppressing classical RAS signalling through the angiotensin type 1 receptor (AT 1 R), the identification of a counter-regulatory axis of the RAS signalling via the angiotensin type 2 receptor (AT 2 R) and Mas receptor has renewed interest in targeting the RAS. This review describes RAS signalling in the brain and the potential of targeting the Mas receptor and AT 2 R in preclinical models of ischaemic stroke. The animal and experimental models, and the route and timing of intervention, are considered from a translational perspective.

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Section: At 2 R and Strokementioning

confidence: 99%

The counter regulatory axis of the renin angiotensin system in the brain and ischaemic stroke: Insight from preclinical stroke studies and therapeutic potential

McFall

Nicklin

Work

2020

Cellular Signalling

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“…for its suitable pharmacokinetics parameters, C21 has been successfully completed Phase I clinical trials (Steckelings et al, 2017). This compound has been patented by Viocore Pharma, a pharmaceutical company focused on rare diseases.…”

Section: Clinical Significance Of At2rmentioning

confidence: 99%

Update on Angiotensin II Subtype 2 Receptor: Focus on Peptide and Nonpeptide Agonists

2021

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Angiotensin II (Ang II) is the most dominant effector component of the renin-angiotensin system (RAS) that generally acts through binding to two main classes of G protein-coupled receptors, namely Ang II subtype-1 receptor (AT1R) and angiotensin II subtype-2 receptor (AT2R). Despite some controversial reports, the activation of AT2R generally antagonizes the effects of Ang II binding on AT1R. Studying AT2R signaling, function, and its specific ligands in cell culture or animal studies have confirmed its beneficial effects throughout the body. These characteristics classify AT2R as part of the protective arm of the RAS that, along with functions of Ang (1-7) through Mas receptor signaling modulates the harmful effects of Ang II on AT1R in the activated classical arm of the RAS. Although Ang II is the primary ligand for AT2R, we have summarized other natural or synthetic peptide and nonpeptide agonists with critical evaluation of their structure, mechanism of action, and biological activity.Significance Statement: AT2R is one of the main components of the RAS and has a significant prospective for mediating the beneficial action of the RAS through its protective arm on the body's homeostasis. Targeting AT2R offers substantial clinical application possibilities for modulating various pathological conditions. This review provided concise information regarding the AT2R peptide and nonpeptide agonists and their potential clinical applications for various diseases.

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“…En ratas Zucker obesas con ingesta elevada de sal, hubo reducción de proteinuria y de parámetros de estrés oxidativo 22 . En sujetos normales su administración oral fue bien tolerada y carente de efectos adversos en relación al placebo 23 .…”

Section: Agonistas De Receptores At2unclassified

Nuevas perspectivas en el manejo de la hipertensión

Zárate

2021

Rev. méd. Chile

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New perspectives in the management of arterial hypertensionArterial hypertension is one of the biggest public health problems. The research in this area has been relentless and productive, allowing to identify new pathophysiological mechanisms from which new therapeutic options are under development. Despite the recognized efficacy and tolerability of currently available drugs, a high number of patients still do not comply with treatment and maintain inadequate blood pressure levels. This review summarizes the literature about new pharmacological alternatives to treat hypertension. The development state of these new medications ranges from a preclinical state to their clinical use in hypertensive patients. Technological strategies aiming at increasing the compliance with anti-hypertensive medications are also mentioned.

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[PP.02.17] Successful Completion of a Phase I, Randomized, Double-Blind, Placebo Controlled, Single Ascending Dose Trial for the First in Class Angiotensin At2-Receptor Agonist Compound 21

Cited by 13 publications

References 0 publications

The counter regulatory axis of the renin angiotensin system in the brain and ischaemic stroke: Insight from preclinical stroke studies and therapeutic potential

The counter regulatory axis of the renin angiotensin system in the brain and ischaemic stroke: Insight from preclinical stroke studies and therapeutic potential

Update on Angiotensin II Subtype 2 Receptor: Focus on Peptide and Nonpeptide Agonists

Nuevas perspectivas en el manejo de la hipertensión

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