- |||||||||| Reasanz (serelaxin) / Novartis
Impulse oscillometry differentiates the lungs of elderly with and without metabolic syndrome: a functional and immunological approach () - Feb 11, 2020 - Abstract #ISPRM2020ISPRM_1071;
Since these changes in R 5Hz and R 20Hz may occurs due to airway inflammation and remodeling, the analysis of pro-inflammatory (IL-1beta, p< 0.0001; IL-8, p< 0.001; TNF-alpha, p< 0.04 and Leptin,p< 0.0006), anti-inflammatory cytokines (IL-1ra, IL-10), anti-fibrotic (relaxin 1, relaxin 3 and Klotho) and pro-fibrotic (VEGF, p< 0.0001), revealed that MS induces a pulmonary pro-inflammatory and pro-fibrotic response.Conclusions : We conclude that IOS is an important tool to differentiates the lung function of elderly with and without metabolic syndrome and that elderly with MS present increased airway resistance involving increases in pulmonary pro-inflammatory and pro-fibrotic mediators. This is possible to reduce the Incidence of respiratory comorbidities in elderly patients with MS.
- |||||||||| Reasanz (serelaxin) / Novartis
Journal: Colokinetic effect of an insulin-like peptide 5-related agonist of the RXFP4 receptor. (Pubmed Central) - Jan 29, 2020
We investigated the ability of INSL5-A13 to increase the speed of emptying of a bead from the colon, after expulsion had been slowed by the peripherally restricted opioid agonist, loperamide (1 mg/kg)...Bead expulsion was not accelerated in RXFP4-/- mice. Our data suggest that RXFP4 agonists could be useful in the treatment of constipation.
- |||||||||| Reasanz (serelaxin) / Novartis
Journal: Inter-Organ Growth Coordination Is Mediated by the Xrp1-Dilp8 Axis in Drosophila. (Pubmed Central) - Jan 27, 2020
We show here that the relaxin-like Dilp8 is required for this inter-organ coordination...In addition, we show that the small ribosomal subunit protein RpS12 is required to trigger Xrp1-dependent non-autonomous response. Our work demonstrates that RpS12, Xrp1, and Dilp8 form an independent regulatory module that ensures intra- and inter-organ growth coordination during development.
- |||||||||| Reasanz (serelaxin) / Novartis
Review, Journal: Targeting the relaxin/insulin-like family peptide receptor 1 and 2 with small molecule compounds. (Pubmed Central) - Jan 17, 2020
This review summarizes the development of ML290 and its potential future therapeutic applications in various diseases, including liver fibrosis and cardiovascular diseases. We also discuss the development of small molecule agonists targeting the insulin-like 3 receptor, RXFP2, and propose the potential use of these small molecules in the context of bone and muscle remodeling.
- |||||||||| Reasanz (serelaxin) / Novartis
Review, Journal: Understanding relaxin signalling at the cellular level. (Pubmed Central) - Jan 17, 2020
This review summarises known signalling pathways induced by acute versus chronic treatment with relaxin across a range of cell types, it describes RXFP1 crosstalk with other receptors, signalling pathways activated by other ligands targeting RXFP1, and it also outlines physiological relevance of RXFP1 signalling outputs. Comprehensive understanding of the mechanism of relaxin actions in fibrosis, vasodilation, as well as organ protection, will further support relaxin's clinical potential.
- |||||||||| Reasanz (serelaxin) / Novartis
Review, Journal: Cardioprotective actions of relaxin. (Pubmed Central) - Jan 17, 2020
Relaxin signals primarily through its G protein coupled receptor, the relaxin family peptide receptor-1, to activate multiple signaling pathways and this review summarizes our understanding of these pathways as they relate to the cardioprotective actions of relaxin, focusing on relaxin's anti-fibrotic, anti-arrhythmic and anti-inflammatory properties. Further, this review includes a brief overview of relaxin in clinical trials for heart failure and progress in the development of relaxin mimetics.
- |||||||||| Reasanz (serelaxin) / Novartis
Review, Journal: Relaxin and the 'Milky Way': The lactocrine hypothesis and maternal programming of development. (Pubmed Central) - Jan 17, 2020
Studies designed to test the lactocrine hypothesis provided insights into both short-term effects of milk-borne bioactive factors in the neonate, and long-term consequences of maternal lactocrine programming of endometrial function and fecundity in adults. Thus, RLX led to the 'Milky Way'.
- |||||||||| Reasanz (serelaxin) / Novartis
Review, Journal: Commercial immunoassays for human Relaxin-2. (Pubmed Central) - Jan 17, 2020
The differences in the quality of immunoassays used for detection of serum relaxin should be part of the decisions making process in choosing an assay. While the end user bears the ultimate responsibility to demonstrate the assay is valid for the stated claims, reviewers and editors also share responsibility for quality of published results.
- |||||||||| Reasanz (serelaxin) / Novartis
Review, Journal: Single chain peptide agonists of relaxin receptors. (Pubmed Central) - Jan 17, 2020
This review briefly summarizes the SAR of human relaxin 2 (H2 relaxin) and human relaxin 3 (H3 relaxin) leading to the design and development of single-B-chain only agonists, B7-33 and peptide 5. The physiological functions of these new peptides agonists in cellular and animal models are also described.
- |||||||||| Reasanz (serelaxin) / Novartis
Clinical, Review, Journal: Relaxin-2 for heart failure with preserved ejection fraction (HFpEF): Rationale for future clinical trials. (Pubmed Central) - Jan 17, 2020
The peptide combines short-term hemodynamic advantages, such as moderate blood pressure decline and functional endothelin-1 antagonism, with a wealth of protective effects harboring long-term benefits, such as anti-inflammatory, anti-fibrotic, and anti-oxidative actions. These pleiotropic effects are exerted through a complex and intricate signaling cascade involving the relaxin-family peptide receptor-1, the glucocorticoid receptor, the nitric oxide system, and a cell type-dependent variety of down-stream mediators.
- |||||||||| Reasanz (serelaxin) / Novartis
Review, Journal: Relaxin and extracellular matrix remodeling: Mechanisms and signaling pathways. (Pubmed Central) - Jan 17, 2020
In this review, the general mechanisms underlying fibrotic diseases are described, along with the current state of knowledge regarding cellular targets of relaxin. Finally, an overview is presented summarizing the signaling pathways activated by relaxin and other relaxin family peptide receptor agonists to suppress fibrosis.
- |||||||||| Reasanz (serelaxin) / Novartis
Review, Journal: Emerging roles for the relaxin/RXFP1 system in cancer therapy. (Pubmed Central) - Jan 17, 2020
RXFP1 activation mediates anti-apoptotic functions, angiogenesis and chemoresistance in cancer cells. This minireview summarizes the known biological functions of RXFP1 activation in different cancer entities in-vitro and in-vivo and outlines possible mechanisms to therapeutically address the relaxin-RXFP1 system in cancer cells.
- |||||||||| Reasanz (serelaxin) / Novartis
Review, Journal: Relaxin and fibrosis: Emerging targets, challenges, and future directions. (Pubmed Central) - Jan 17, 2020
Furthermore, it can reduce established scarring by promoting the degradation of aberrant extracellular matrix components. Following on from the review that describes the mechanisms and signaling pathways associated with the extracellular matrix remodeling effects of serelaxin (Ng et al., 2019), this review focuses on newly identified tissue targets of serelaxin therapy in fibrosis, and the limitations associated with (se)relaxin research.
- |||||||||| Reasanz (serelaxin) / Novartis
Review, Journal: Editorial to the mini-review series on Relaxin, Related Peptides and Receptors? (Pubmed Central) - Jan 17, 2020
Following on from the review that describes the mechanisms and signaling pathways associated with the extracellular matrix remodeling effects of serelaxin (Ng et al., 2019), this review focuses on newly identified tissue targets of serelaxin therapy in fibrosis, and the limitations associated with (se)relaxin research. No abstract available
- |||||||||| Reasanz (serelaxin) / Novartis
Review, Journal: G Protein-Coupled Receptor Systems and Their Role in Cellular Senescence. (Pubmed Central) - Jan 12, 2020
Emerging data now suggests the involvement of GPCRs and their associated proteins in the development of cellular senescence. With the proven efficacy of therapeutic GPCR targeting, it is reasonable to now consider GPCRs as potential platforms to control cellular senescence and the consequently, age-related disorders.
- |||||||||| Reasanz (serelaxin) / Novartis
Journal: Design and Synthesis of Potent, Long-Acting Lipidated Relaxin-2 Analogs. (Pubmed Central) - Jan 5, 2020
The resultant novel relaxin analog, R9-13, represents the first long-acting relaxin-2 analog and could potentially improve the clinical efficacy and outcome for this important peptide hormone. This semisynthetic methodology could also be applied to other cysteine-rich peptides and proteins for half-life extension.
- |||||||||| Reasanz (serelaxin) / Novartis
Retrospective data, Journal: Effects of serelaxin in patients admitted for acute heart failure: a meta-analysis. (Pubmed Central) - Dec 31, 2019
Administration of intravenous serelaxin to patients admitted for AHF was associated with a highly significant reduction in the risk of 5-day worsening heart failure and in changes in renal function markers, but not length of stay, or cardiovascular death, or heart or renal failure rehospitalization. Serelaxin administration was safe and associated with a significant reduction in all-cause mortality.
- |||||||||| Reasanz (serelaxin) / Novartis
Journal: A novel approach for preparing disulfide-rich peptide-KLH conjugate applicable to the antibody production. (Pubmed Central) - Dec 20, 2019
In this study, to expand the applicability of this method to wide variety of peptides, we newly designed a novel thiol probe enabling the conjugation between various peptides and KLH, and applied it to produce the antiserum against relaxin-like peptide of a starfish Asterias amurensis. The antiserum obtained here showed high antibody-titer and good specificity, strongly suggesting that the method developed in this study is applicable to various peptides.
- |||||||||| Reasanz (serelaxin) / Novartis
Molecular Mechanisms of Estrogen Receptor Enhancer Assembly and Function (Room 157) - Dec 14, 2019 - Abstract #ENDO2020ENDO_585;
The signaling pathways mediated by these hormones (steroid versus polypeptide) converge on ERα enhancers to regulate estrogen-dependent gene expression in physiologically relevant ways. Collectively, our analyses are providing new insights into enhancer complex assembly and function in a variety of biological systems.
- |||||||||| Reasanz (serelaxin) / Novartis
Preclinical, Journal: Exploring electrostatic interactions of relaxin family peptide receptor 3 and 4 with ligands using a NanoBiT-based binding assay. (Pubmed Central) - Nov 29, 2019
Based on binding complementation of mutant ligands towards mutant receptors, we deduced possible electrostatic interactions of the agonist and antagonist with both RXFP3 and RXFP4: their B-chain C-terminal Arg residue interacts with the deeply buried Glu residue in the WxxExxxD motif of both receptors, and one or two of their B-chain central Arg residues interact with the shallowly buried Asp residue in the WxxExxxD motif of both receptors. Our present work shed new light on the interaction mechanism of RXFP3 and RXFP4 with agonists and antagonists, and also provided a novel approach for interaction studies of some plasma membrane receptors with their ligands.
- |||||||||| Endostar (recombinant human endostatin) / Simcere, Reasanz (serelaxin) / Novartis
Journal: Fibrosis and the bladder, implications for function ICI-RS 2017. (Pubmed Central) - Nov 21, 2019
The administration of recombinant INSL6 protein could have utility for the treatment of heart failure and cardiac fibrosis. The conclusion that reduced bladder contractile function with increased fibrosis is due largely to the replacement of detrusor with ECM offers a way forward for future research to consider approaches that will restore bladder function by reducing ECM deposition.
- |||||||||| Reasanz (serelaxin) / Novartis
Review, Journal: Which molecular targets do we need to focus on to improve lower urinary tract dysfunction? ICI-RS 2017. (Pubmed Central) - Nov 21, 2019
The conclusion that reduced bladder contractile function with increased fibrosis is due largely to the replacement of detrusor with ECM offers a way forward for future research to consider approaches that will restore bladder function by reducing ECM deposition. New molecular targets for drugs aiming at improvement of voiding function can be identified, but their translational impact remains to be established.
- |||||||||| Reasanz (serelaxin) / Novartis
Review, Journal: Relaxin in liver transplantation: A personal perspective. (Pubmed Central) - Nov 19, 2019
BMI and eGFR were identified as the main covariates explaining inter-subject variability on clearance; however the impact of these covariates on steady-state concentration was moderate and therefore unlikely to be clinically relevant. No abstract available
- |||||||||| Reasanz (serelaxin) / Novartis
Preclinical, Journal: Increased Preeclampsia Risk and Reduced Aortic Compliance With In Vitro Fertilization Cycles in the Absence of a Corpus Luteum. (Pubmed Central) - Nov 19, 2019
Programmed frozen embryo transfer cycles (0 CL) were associated with higher rates of preeclampsia (12.8% versus 3.9%; P=0.02) and preeclampsia with severe features (9.6% versus 0.8%; P=0.002) compared with modified natural frozen embryo transfer cycles (1 CL). In common in vitro fertilization protocols, absence of the CL perturbed the maternal circulation in early pregnancy and increased the incidence of preeclampsia.
- |||||||||| Simdax (levosimendan IV) / AbbVie
Clinical, Review, Journal: Short-Term Therapies for Treatment of Acute and Advanced Heart Failure-Why so Few Drugs Available in Clinical Use, Why Even Fewer in the Pipeline? (Pubmed Central) - Nov 8, 2019
Recent set backs in expected clinical trials for new agents in acute heart failure (AHF) (omecamtiv, serelaxine, ularitide) left a field desolately empty, where only few drugs have been approved for clinical use, for example, levosimendan and nesiritide. In this consensus opinion paper, experts from 26 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Israel, Italy, The Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, Turkey, U.K. and Ukraine) analyse the situation in details also by help of artificial intelligence applied to bibliographic searches, try to distil some lesson-learned to avoid that future projects would make the same mistakes as in the past and recommend how to lead a successful development project in this field in dire need of new agents.
- |||||||||| Reasanz (serelaxin) / Novartis
Preclinical, Journal: Relaxin-2 therapy reverses radiation-induced fibrosis and restores bladder function in mice. (Pubmed Central) - Oct 24, 2019
These results provide a mechanism by which H3 relaxin alleviates NLRP3 inflammasome-mediated collagen synthesis through the inhibition of ROS and P2X7R under HG conditions and suggest that H3 relaxin represents a potential drug for alleviating cardiac fibrosis in diabetic cardiomyopathy. hRLX2 may be a new therapeutic option for rescuing bladders with chronic radiation cystitis.
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