View source for Serelaxin

{{Drugbox
| IUPAC_name = L-Serine, L-α-aspartyl-L-seryl-L-tryptophyl-L-methionyl-L-α-glutamyl-L-α-glutamyl-L-valylL-isoleucyl-L-lysyl-L-leucyl-L-cysteinylglycyl-L-arginyl-L-α-glutamyl-L-leucyl-L-valyl-L- arginyl-L-alanyl-L-glutaminyl-L-isoleucyl-L-alanyl-L-isoleucyl-L-cysteinylglycyl-L- methionyl-L-seryl-L-threonyl-L-tryptophyl-, cyclic (11→11'),(23→24')-bis(disulfide) with 5-oxo-L-prolyl-L-leucyl-L-tyrosyl-L-seryl-L-alanyl-L-leucyl-L-alanyl-L-asparaginyl-L-lysyl-L- cysteinyl-L-cysteinyl-L-histidyl-L-valylglycyl-L-cysteinyl-L-threonyl-L-lysyl-L-arginyl-L- seryl-L-leucyl-L-alanyl-L-arginyl-L-phenylalanyl-L-cysteine cyclic (10'→15')-disulfide

<!--Clinical data-->
| tradename = 
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_category = N/A
| legal_AU = <!-- Unscheduled / S2 / S4 / S8 -->
| legal_status = Investigational
| routes_of_administration = [[Intravenous]]
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = NA

<!--Identifiers-->
| ATC_prefix = C01
| ATC_suffix = DX21
| CAS_number = 99489-94-8

<!--Chemical data-->
| C=256  | H=408  | N=74  | O=74  | S=8
| molecular_weight = 5963 g/mol 
}}

'''Serelaxin''' ('''RLX030''') is an investigational drug for the treatment of acute [[heart failure]] (AHF), targeting the [[relaxin receptor]]. Serelaxin is a recombinant form of human [[relaxin]]-2, a hormone that (among other functions) is produced during pregnancy and mediates the haemodynamic changes that occur during this time,<ref name="Spreitzer" /><ref name="aerztezeitung" /> such as increased blood output of the heart and blood flow in the kidney.<ref name="pmid21613576" />  Human-relaxin-2 mediates vasodilation (widening of blood vessels) by increasing the production of [[nitric oxide]] (NO), a potent [[vasodilator]].<ref name="Tousoulis" />  Activation of the relaxin receptor [[RXFP1]] activates several enzymes in a [[phosphorylation cascade]] that eventually results in the activation of NO synthase in endothelial cells and the subsequent production of NO.<ref name="Bathgate" />  Relaxin can also bind to a secondary receptor, endothelial B receptor,{{Clarify|date=March 2014}} which is upregulated as a result of the previous pathway.<ref name="Miyares" />  Relaxin binding to endothelial B receptor on endothelial cells also induces vasodilation.<ref name="Teichman1" />

Relaxin causes vasodilation by an indirect mechanism, where it inhibits the potent vasoconstrictors angiotensin II and endothelin.<ref name="Teichman2" />  
In addition to vasodilation, the effects of relaxin are also seen in the kidneys, by significantly increasing [[creatinine]] clearance,<ref name="Ponikowski" /> which is a measure of kidney function, as well as increased renal blood flow.<ref name="Teichman1" />
Relaxin also functions as a cardiac stimulant.<ref name="Bathgate" />  Studies have demonstrated that relaxin increases calcium sensitivity of cardiac [[myofilament]]s as well as increasing phosphorylation of the myofilaments by [[protein kinase C]] (PKC).<ref name="Shaw" />  These modifications both function to increase the force generated by the myofilaments without increasing the energy consumption of the cardiac myocytes.<ref name="Shaw" />  Thus relaxin and serelaxin can increase [[stroke volume]], the amount of blood pumped per heart beat, without increasing the energy demand on the already strained heart of acute heart failure patients.

==Acute heart failure==
Serelaxin is currently undergoing clinical trials in patients with acute heart failure,<ref name="Teerlink" /> and is being developed by [[Novartis]].  Serelaxin has completed several clinical trials as a therapy for AHF.  Phase I trials examined safety and tolerability,<ref name="Du" /> while phase II trials evaluated its haemodynamic effects and symptom relief.  The Pre-RELAX-AHF phase II trial administered a dose of 30&nbsp;µg/kg/day and showed a decrease in blood pressure, improved [[dyspnoea]], and increased renal blood flow.<ref name="Teichman1" />  In phase III the RELAX-AHF trial gave a 48hr intravenous infusion of the same dose.<ref name="King" />  It significantly improved patients' dyspnoea, resulted in a 30% reduction in worsening of heart failure symptoms, a decreased hospital stay and a reduction in signs and symptoms of congestion.<ref name="Teerlink" /><ref name="Filippatos" />  The FDA has granted serelaxin "breakthrough therapy" designation, meant to expedite the development and review of drugs for life threatening conditions and is set to be reviewed in February 2014.<ref name="Novartis" />

== References ==
{{reflist|35em|refs=
<ref name="Teerlink">{{cite journal|last=Teerlink|first=John R|coauthors=Cotter, Gad; Davison, Beth A; Felker, G Michael; Filippatos, Gerasimos; Greenberg, Barry H; Ponikowski, Piotr; Unemori, Elaine; Voors, Adriaan A; Adams, Kirkwood F; Dorobantu, Maria I; Grinfeld, Liliana R; Jondeau, Guillaume; Marmor, Alon; Masip, Josep; Pang, Peter S; Werdan, Karl; Teichman, Sam L; Trapani, Angelo; Bush, Christopher A; Saini, Rajnish; Schumacher, Christoph; Severin, Thomas M; Metra, Marco|title=Serelaxin, recombinant human relaxin-2, for treatment of acute heart failure (RELAX-AHF): a randomised, placebo-controlled trial|journal=The Lancet|date=1 November 2012|doi=10.1016/S0140-6736(12)61855-8|url=http://www.sciencedirect.com/science/article/pii/S0140673612618558}}</ref>
<ref name="Spreitzer">{{cite journal| author = H. Spreitzer| date = 4 March 2013| title = Neue Wirkstoffe – Serelaxin| journal = Österreichische Apothekerzeitung| issue = 5/2013| page = 36| language = German}}</ref>
<ref name=Tousoulis>{{cite journal|last=Tousoulis|first=D|coauthors=Kampoli, A., Papageorgiou, C., Stefanadis, C.|title=The role of nitric oxide on endothelial function|journal=Curr Vasc Pharmacol|year=2012|volume=10|pages=4–18}}</ref> 
<ref name="aerztezeitung">{{cite web|url=http://www.aerztezeitung.de/medizin/krankheiten/herzkreislauf/herzinsuffizienz/article/826906/fortschritt-sicht-schwangerschaftshormon-herzschwaeche.html?sh=1&h=-655181939|journal=ÄrzteZeitung|date=23 November 2012|title=Schwangerschaftshormon gegen Herzschwäche|trans_title=Pregnancy hormone against heart failure|author=Dirk Einecke}}</ref>
<ref name="pmid21613576">{{cite journal | author = Conrad KP | title = Maternal vasodilation in pregnancy: the emerging role of relaxin | journal = Am. J. Physiol. Regul. Integr. Comp. Physiol. | volume = 301 | issue = 2 | pages = R267–75 |date=August 2011 | pmid = 21613576 | pmc = 3154715 | doi = 10.1152/ajpregu.00156.2011 }}</ref>
<ref name="Bathgate">{{cite journal|last=Bathgate|first=R.|coauthors=Halls, M., van der Westhuizen, E., Callander, G., Kocan, M. et al|title=The Relaxin family peptides and their receptors|journal=Physiol Rev|year=2013|volume=93|pages=405–480}}</ref> 
<ref name="Miyares">{{cite journal|last=Miyares|first=M|coauthors=Davis, K.|title=Serelaxin, a breakthrough investigational intravenous agent for acute heart failure|journal=P.T|year=2013|volume=38|pages=606–611}}</ref> 
<ref name="Teichman1">{{cite journal|last=Teichman|first=S|coauthors=Unemori, E., Teerlink, J., Cotter, G., Metra, M.|title=Relaxin, review of biology and potential role in treating heart failure|journal=Curr Heart Fail Rep|year=2010|volume=75|pages=75–82}}</ref> 
<ref name="Teichman2">{{cite journal|last=Teichman|first=S|coauthors=Unemori, E., Dschietzig, T., Conrad, K., Voors, A. et al|title=Relaxin, a pleiotropic vasodilator for the treatment of heart failure|journal=Heart Fail Rev|year=2009|volume=14|pages=321–329}}</ref> 
<ref name="Ponikowski">{{cite journal|last=Ponikowski|first=P.|coauthors=Mitroic, V., Rude, M., Fernandez, A., Voors, A. et al|title=A randomized, double-blind, placebo controlled, multicentre study to assess haemodynamic effects of serelaxin in patients with acute heart failure|journal=Eur Heart J|year=2014|volume=35|pages=431–441}}</ref> 
<ref name="Shaw">{{cite journal|last=Shaw|first=E.|coauthors=Wood, P., Kulpa, J., Yang, F., Summerlee, A. et al|title=Relaxin alters cardiac myofilament function through a PKC-dependent pathway|journal=Am J Physiol Heart Circ Physiol|year=2009|volume=297|pages=29–36}}</ref> 
<ref name="Du">{{cite journal|last=Du|first=X.|coauthors=Hewitson, T., Nguyen, M., Samuel, C.|title=Therapeutic effects of Serelaxin in acute heart failure|journal=Circ J|year=2014|volume=12|pages=6–19}}</ref> 
<ref name="King">{{cite journal|last=King|first=A|title=Heart failure-promising data for Serelaxin|journal=Nat Rev Cardiol|year=2013|volume=10|page=3}}</ref> 
<ref name="Filippatos">{{cite journal|last=Filippatos|first=G.|coauthors=Teerlink, J., Farmakis, D., Cotter, G., Davison, B. et al|title=Serelaxin in acute heart failure patients with preserved left ventricular ejection fraction: results from the RELAX-AHF trial|journal=Eur Heart|year=2014|volume=89|pages=90–103}}</ref> 
<ref name="Novartis">{{cite web|last=Novartis Global|title=FDA grants breakthrough designation to Novartis' serelaxin (RLX030) for acute heart failure|url=http://www.novartis.com/newsroom/media-releases/en/2013/1711047.shtml|publisher=Novartis Global}}</ref>
}}

{{Vasodilators used in cardiac diseases}}

[[Category:Cardiovascular Drugs]]
[[Category:Drugs]]
[[Category:Vasodilators]]