412:, and increased renal blood flow. In phase III the RELAX-AHF trial gave a 48hr intravenous infusion of the same dose. 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. The FDA granted serelaxin "breakthrough therapy" designation, meant to expedite the development and review of drugs for life-threatening conditions. On 22 March 2017, Novartis announced that the global Phase III study of serelaxin in patients with acute heart failure did not meet its primary endpoints.
243:
137:
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
408:. Serelaxin has completed several clinical trials as a therapy for AHF. Phase I trials examined safety and tolerability, while phase II trials evaluated its haemodynamic effects and symptom relief. The Pre-RELAX-AHF phase II trial administered a dose of 30 μg/kg/day and showed a decrease in blood pressure, improved
358:-2, a hormone that (among other functions) is produced during pregnancy and mediates the haemodynamic changes that occur during this time, such as increased blood output of the heart and blood flow in the kidney. Human-relaxin-2 mediates vasodilation (widening of blood vessels) by increasing the production of
374:
that eventually results in the activation of NO synthase in endothelial cells and the subsequent production of NO. Relaxin can also bind to a secondary receptor, endothelial B receptor, which is upregulated as a result of the previous pathway. Relaxin binding to endothelial B receptor on endothelial
136:
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-
378:
Relaxin causes vasodilation by an indirect mechanism, where it inhibits the potent vasoconstrictors angiotensin II and endothelin. In addition to vasodilation, the effects of relaxin are also seen in the kidneys, by significantly increasing
839:
Teerlink JR, Cotter G, Davison BA, Felker GM, Filippatos G, Greenberg BH, et al. (January 2013). "Serelaxin, recombinant human relaxin-2, for treatment of acute heart failure (RELAX-AHF): a randomised, placebo-controlled trial".
383:
clearance, which is a measure of kidney function, as well as increased renal blood flow. Relaxin also functions as a cardiac stimulant. Studies have demonstrated that relaxin increases calcium sensitivity of cardiac
465:
1079:
1040:
392:(PKC). These modifications both function to increase the force generated by the myofilaments without increasing the energy consumption of the cardiac myocytes. Thus relaxin and serelaxin can increase
74:
1072:
1356:
1065:
1048:
801:
Shaw EE, Wood P, Kulpa J, Yang FH, Summerlee AJ, Pyle WG (July 2009). "Relaxin alters cardiac myofilament function through a PKC-dependent pathway".
751:"A randomized, double-blind, placebo-controlled, multicentre study to assess haemodynamic effects of serelaxin in patients with acute heart failure"
1022:
396:, the amount of blood pumped per heart beat, without increasing the energy demand on the already strained heart of acute heart failure patients.
570:
Bathgate RA, Halls ML, van der
Westhuizen ET, Callander GE, Kocan M, Summers RJ (January 2013). "Relaxin family peptides and their receptors".
1307:
1351:
532:
Tousoulis D, Kampoli AM, Tentolouris C, Papageorgiou N, Stefanadis C (January 2012). "The role of nitric oxide on endothelial function".
975:"Serelaxin in acute heart failure patients with preserved left ventricular ejection fraction: results from the RELAX-AHF trial"
128:
104:
1150:
1113:
182:
1324:
222:
1312:
371:
60:
1125:
1041:"Novartis provides update on Phase III study of RLX030 (serelaxin) in patients with acute heart failure"
1026:
1119:
749:
Ponikowski P, Mitrovic V, Ruda M, Fernandez A, Voors AA, Vishnevsky A, et al. (February 2014).
700:
Teichman SL, Unemori E, Dschietzig T, Conrad K, Voors AA, Teerlink JR, et al. (December 2009).
238:
332:
146:
973:
Filippatos G, Teerlink JR, Farmakis D, Cotter G, Davison BA, Felker GM, et al. (April 2014).
955:
865:
42:
1057:
1004:
947:
906:
857:
818:
780:
731:
682:
628:
587:
549:
514:
32:
1023:"FDA grants breakthrough designation to Novartis' serelaxin (RLX030) for acute heart failure"
1130:
1105:
994:
986:
937:
896:
849:
810:
770:
762:
721:
713:
672:
664:
618:
579:
541:
504:
496:
389:
336:
259:
404:
Serelaxin has undergone clinical trials in patients with acute heart failure, conducted by
191:
155:
1155:
1092:
242:
1318:
999:
974:
775:
750:
726:
701:
677:
652:
623:
607:"Serelaxin, a 'breakthrough' investigational intravenous agent for acute heart failure"
606:
509:
484:
853:
1345:
393:
340:
869:
1253:
1198:
1096:
959:
431:
359:
87:
82:
489:
American
Journal of Physiology. Regulatory, Integrative and Comparative Physiology
1278:
1243:
1203:
1182:
1163:
1140:
1135:
1088:
814:
385:
363:
67:
990:
766:
583:
545:
500:
339:. It was also under development in other places in the world, including in the
1293:
1273:
1268:
1263:
1258:
1238:
1233:
1213:
1145:
942:
925:
717:
668:
380:
298:
166:
901:
884:
1248:
1228:
1208:
1173:
1008:
951:
910:
861:
822:
784:
735:
686:
632:
591:
553:
518:
20:
1288:
1223:
653:"Relaxin: review of biology and potential role in treating heart failure"
409:
405:
1218:
702:"Relaxin, a pleiotropic vasodilator for the treatment of heart failure"
355:
344:
328:
651:
Teichman SL, Unemori E, Teerlink JR, Cotter G, Metra M (June 2010).
211:
485:"Maternal vasodilation in pregnancy: the emerging role of relaxin"
367:
803:
American
Journal of Physiology. Heart and Circulatory Physiology
348:
202:
1061:
388:
as well as increasing phosphorylation of the myofilaments by
227:
449:
Spreitzer H (4 March 2013). "Neue
Wirkstoffe – Serelaxin".
885:"Therapeutic effects of serelaxin in acute heart failure"
1191:
1172:
1104:
468:[Pregnancy hormone against heart failure].
297:
258:
253:
221:
201:
181:
165:
145:
119:
103:
98:
73:
59:
41:
31:
26:
351:, but ultimately was not marketed in these areas.
883:Du XJ, Hewitson TD, Nguyen MN, Samuel CS (2014).
154:
1073:
926:"Heart failure. Promising data for serelaxin"
426:
424:
8:
19:
834:
832:
646:
644:
642:
466:"Schwangerschaftshormon gegen Herzschwäche"
1080:
1066:
1058:
565:
563:
241:
1357:Drugs acting on the cardiovascular system
998:
941:
900:
774:
725:
676:
622:
508:
354:Serelaxin is a recombinant form of human
190:
796:
794:
420:
327:) is a medication which is marketed in
237:
133:
18:
605:Miyares MA, Davis KA (October 2013).
366:. Activation of the relaxin receptor
7:
86:
210:
14:
1025:. Novartis Global. Archived from
438:. Springer Nature Switzerland AG.
375:cells also induces vasodilation.
451:Österreichische Apothekerzeitung
276:
270:
370:activates several enzymes in a
464:Einecke D (23 November 2012).
288:
282:
264:
1:
854:10.1016/S0140-6736(12)61855-8
657:Current Heart Failure Reports
534:Current Vascular Pharmacology
1151:Pentaerythritol tetranitrate
1045:Global Novartis News Archive
1352:Drugs developed by Novartis
815:10.1152/ajpheart.00482.2008
1373:
930:Nature Reviews. Cardiology
584:10.1152/physrev.00001.2012
546:10.2174/157016112798829760
501:10.1152/ajpregu.00156.2011
323:; developmental code name
254:Chemical and physical data
1302:
943:10.1038/nrcardio.2012.174
718:10.1007/s10741-008-9129-3
669:10.1007/s11897-010-0010-z
483:Conrad KP (August 2011).
453:(in German) (5/2013): 36.
124:
991:10.1093/eurheartj/eht497
902:10.1253/circj.cj-14-0014
767:10.1093/eurheartj/eht459
924:King A (January 2013).
372:phosphorylation cascade
1126:Isosorbide mononitrate
979:European Heart Journal
755:European Heart Journal
432:"Serelaxin - Novartis"
706:Heart Failure Reviews
572:Physiological Reviews
335:(AHF), targeting the
331:for the treatment of
1120:Isosorbide dinitrate
889:Circulation Journal
400:Acute heart failure
333:acute heart failure
23:
1329:Never to phase III
1339:
1338:
1106:Nitrovasodilators
314:
313:
223:CompTox Dashboard
16:Chemical compound
1364:
1131:Itramin tosilate
1093:cardiac diseases
1082:
1075:
1068:
1059:
1053:
1052:
1051:on 10 July 2018.
1047:. Archived from
1037:
1031:
1030:
1029:on 2 March 2014.
1019:
1013:
1012:
1002:
970:
964:
963:
945:
921:
915:
914:
904:
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836:
827:
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798:
789:
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746:
740:
739:
729:
697:
691:
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680:
648:
637:
636:
626:
602:
596:
595:
567:
558:
557:
529:
523:
522:
512:
480:
474:
473:
461:
455:
454:
446:
440:
439:
428:
390:protein kinase C
337:relaxin receptor
309:
307:
290:
284:
278:
272:
266:
246:
245:
231:
229:
214:
194:
158:
90:
24:
22:
1372:
1371:
1367:
1366:
1365:
1363:
1362:
1361:
1342:
1341:
1340:
1335:
1334:
1319:Clinical trials
1298:
1187:
1168:
1156:Propatylnitrate
1100:
1086:
1056:
1039:
1038:
1034:
1021:
1020:
1016:
985:(16): 1041–50.
972:
971:
967:
923:
922:
918:
882:
881:
877:
848:(9860): 29–39.
838:
837:
830:
800:
799:
792:
748:
747:
743:
699:
698:
694:
650:
649:
640:
604:
603:
599:
569:
568:
561:
531:
530:
526:
482:
481:
477:
463:
462:
458:
448:
447:
443:
430:
429:
422:
418:
402:
362:(NO), a potent
305:
303:
293:
287:
281:
275:
269:
249:
225:
217:
197:
177:
161:
141:
138:
132:
131:
115:
112:Investigational
94:
62:
55:
44:
17:
12:
11:
5:
1370:
1368:
1360:
1359:
1354:
1344:
1343:
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1316:
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1300:
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1216:
1211:
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1201:
1195:
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1189:
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1166:
1161:
1158:
1153:
1148:
1143:
1138:
1133:
1128:
1123:
1117:
1110:
1108:
1102:
1101:
1087:
1085:
1084:
1077:
1070:
1062:
1055:
1054:
1032:
1014:
965:
916:
875:
828:
790:
741:
692:
638:
617:(10): 606–11.
597:
559:
524:
495:(2): R267-75.
475:
456:
441:
419:
417:
414:
401:
398:
312:
311:
301:
295:
294:
291:
285:
279:
273:
267:
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239:DTXSID40244082
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109:
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100:
96:
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92:
79:
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71:
70:
65:
63:administration
57:
56:
54:
53:
49:
47:
39:
38:
35:
29:
28:
15:
13:
10:
9:
6:
4:
3:
2:
1369:
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1144:
1142:
1139:
1137:
1134:
1132:
1129:
1127:
1124:
1121:
1118:
1115:
1114:Nitroglycerin
1112:
1111:
1109:
1107:
1103:
1098:
1094:
1090:
1083:
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953:
949:
944:
939:
935:
931:
927:
920:
917:
912:
908:
903:
898:
895:(3): 542–52.
894:
890:
886:
879:
876:
871:
867:
863:
859:
855:
851:
847:
843:
835:
833:
829:
824:
820:
816:
812:
809:(1): H29-36.
808:
804:
797:
795:
791:
786:
782:
777:
772:
768:
764:
761:(7): 431–41.
760:
756:
752:
745:
742:
737:
733:
728:
723:
719:
715:
711:
707:
703:
696:
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639:
634:
630:
625:
620:
616:
612:
608:
601:
598:
593:
589:
585:
581:
578:(1): 405–80.
577:
573:
566:
564:
560:
555:
551:
547:
543:
539:
535:
528:
525:
520:
516:
511:
506:
502:
498:
494:
490:
486:
479:
476:
471:
470:Ärzte-Zeitung
467:
460:
457:
452:
445:
442:
437:
433:
427:
425:
421:
415:
413:
411:
407:
399:
397:
395:
394:stroke volume
391:
387:
382:
376:
373:
369:
365:
361:
357:
352:
350:
346:
342:
341:United States
338:
334:
330:
326:
322:
318:
302:
300:
296:
263:
261:
257:
252:
244:
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236:
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118:
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97:
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78:
76:
72:
69:
66:
64:
58:
51:
50:
48:
46:
40:
36:
34:
30:
27:Clinical data
25:
1283:
1254:Levosimendan
1199:Benziodarone
1176:vasodilators
1089:Vasodilators
1049:the original
1044:
1035:
1027:the original
1017:
982:
978:
968:
933:
929:
919:
892:
888:
878:
845:
841:
806:
802:
758:
754:
744:
712:(4): 321–9.
709:
705:
695:
663:(2): 75–82.
660:
656:
614:
610:
600:
575:
571:
537:
533:
527:
492:
488:
478:
472:(in German).
469:
459:
450:
444:
436:Adis Insight
435:
403:
386:myofilaments
377:
360:nitric oxide
353:
324:
320:
319:(brand name
316:
315:
105:Legal status
99:Legal status
1315:from market
1279:Prenylamine
1244:Hexobendine
1204:Carbocromen
1183:Flosequinan
1164:Trolnitrate
1160:Tenitramine
1141:Molsidomine
1136:Linsidomine
540:(1): 4–18.
364:vasodilator
310: g·mol
120:Identifiers
68:Intravenous
33:Trade names
1346:Categories
1294:Vericiguat
1274:Pimobendan
1269:Oxyfedrine
1264:Nicorandil
1259:Nesiritide
1239:Heptaminol
1234:Gapicomine
1214:Cloridarol
1146:Nicorandil
416:References
381:creatinine
299:Molar mass
192:W0122B976Y
167:ChemSpider
156:99489-94-8
147:CAS Number
129:IUPAC name
1325:Phase III
1313:Withdrawn
1284:Serelaxin
1249:Imolamine
1229:Etafenone
1209:Cinepazet
1174:Quinolone
611:P & T
317:Serelaxin
61:Routes of
43:Pregnancy
21:Serelaxin
1289:Trapidil
1224:Efloxate
1091:used in
1009:24316514
952:23165078
936:(1): 3.
911:24451687
870:42821305
862:23141816
823:19429819
785:24255129
736:19101795
687:20424993
633:24391379
592:23303914
554:22112350
519:21613576
410:dyspnoea
406:Novartis
75:ATC code
45:category
1219:Dilazep
1000:3992428
960:2399731
776:3924183
727:2772950
678:2875472
624:3875246
510:3154715
356:relaxin
325:RLX-030
321:Reasanz
260:Formula
91:)
85: (
83:C01DX21
37:Reasanz
1308:WHO-EM
1192:Others
1007:
997:
958:
950:
909:
868:
860:
842:Lancet
821:
783:
773:
734:
724:
685:
675:
631:
621:
590:
552:
517:
507:
347:, and
345:Europe
329:Russia
212:D10488
956:S2CID
866:S2CID
368:RXFP1
1097:C01D
1005:PMID
948:PMID
907:PMID
858:PMID
819:PMID
781:PMID
732:PMID
683:PMID
629:PMID
588:PMID
550:PMID
515:PMID
349:Asia
203:KEGG
183:UNII
174:none
995:PMC
987:doi
938:doi
897:doi
850:doi
846:381
811:doi
807:297
771:PMC
763:doi
722:PMC
714:doi
673:PMC
665:doi
619:PMC
580:doi
542:doi
505:PMC
497:doi
493:301
308:.00
306:963
274:408
268:256
228:EPA
88:WHO
52:N/A
1348::
1321::
1043:.
1003:.
993:.
983:35
981:.
977:.
954:.
946:.
934:10
932:.
928:.
905:.
893:78
891:.
887:.
864:.
856:.
844:.
831:^
817:.
805:.
793:^
779:.
769:.
759:35
757:.
753:.
730:.
720:.
710:14
708:.
704:.
681:.
671:.
659:.
655:.
641:^
627:.
615:38
613:.
609:.
586:.
576:93
574:.
562:^
548:.
538:10
536:.
513:.
503:.
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