Ularitide

• CAT Number: I037817
• CAS Number: 118812-69-4
• Molecular Formula: C145H234N52O44S3
• Molecular Weight: 3505.96
• Purity: 98%
• Synonyms: Ularitide; Human urodilatin; ANP 95-126; CDD 95-126
• Solubility: Soluble in DMSO
• Appearance: Solid powder
• Storage: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
• IUPAC Name: L-Threonyl-L-alanyl-L-prolyl-L-arginyl-L-seryl-L-leucyl-L-arginyl-L-arginyl-L-seryl-L-seryl-L-cysteinyl-L-phenylalanylglycylglycyl-L-arginyl-L-methionyl-L-aspartyl-L-arginyl-L-isoleucylglycyl-L-alanyl-L-glutaminyl-L-serylglycyl-L-leucylglycyl-L-cysteinyl-L-asparaginyl-L-seryl-L-phenylalanyl-L-arginyl-L-tyrosine cyclic (11->27)-disulfide
• InChI: InChI=1S/C145H234N52O44S3/c1-11-72(6)112-137(238)171-60-106(208)172-73(7)113(214)177-86(40-41-103(146)205)122(223)190-95(63-198)116(217)170-61-108(210)175-88(51-70(2)3)114(215)169-62-109(211)176-100(133(234)187-92(56-104(147)206)127(228)193-97(65-200)130(231)186-91(54-77-27-16-13-17-28-77)126(227)180-82(31-20-45-163-142(153)154)119(220)189-94(139(240)241)55-78-36-38-79(204)39-37-78)68-243-244-69-101(134(235)185-90(53-76-25-14-12-15-26-76)115(216)168-58-105(207)167-59-107(209)174-80(29-18-43-161-140(149)150)117(218)182-87(42-50-242-10)123(224)188-93(57-110(212)213)128(229)181-85(124(225)196-112)34-23-48-166-145(159)160)195-132(233)99(67-202)194-131(232)98(66-201)192-120(221)83(32-21-46-164-143(155)156)178-118(219)81(30-19-44-162-141(151)152)179-125(226)89(52-71(4)5)184-129(230)96(64-199)191-121(222)84(33-22-47-165-144(157)158)183-135(236)102-35-24-49-197(102)138(239)74(8)173-136(237)111(148)75(9)203/h12-17,25-28,36-39,70-75,80-102,111-112,198-204H,11,18-24,29-35,40-69,148H2,1-10H3,(H2,146,205)(H2,147,206)(H,167,207)(H,168,216)(H,169,215)(H,170,217)(H,171,238)(H,172,208)(H,173,237)(H,174,209)(H,175,210)(H,176,211)(H,177,214)(H,178,219)(H,179,226)(H,180,227)(H,181,229)(H,182,218)(H,183,236)(H,184,230)(H,185,235)(H,186,231)(H,187,234)(H,188,224)(H,189,220)(H,190,223)(H,191,222)(H,192,221)(H,193,228)(H,194,232)(H,195,233)(H,196,225)(H,212,213)(H,240,241)(H4,149,150,161)(H4,151,152,162)(H4,153,154,163)(H4,155,156,164)(H4,157,158,165)(H4,159,160,166)/t72-,73-,74-,75+,80-,81-,82-,83-,84-,85-,86-,87-,88-,89-,90-,91-,92-,93-,94-,95-,96-,97-,98-,99-,100-,101-,102-,111-,112-/m0/s1
• InChIKey: IUCCYQIEZNQWRS-DWWHXVEHSA-N
• SMILES: CC[C@@H]([C@@H]1NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC(CNC(CNC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H]2CCCN2C([C@@H](NC([C@H]([C@H](O)C)N)=O)C)=O)=O)CCCNC(N)=N)=O)CO)=O)CC(C)C)=O)CCCNC(N)=N)=O)CCCNC(N)=N)=O)CO)=O)CO)=O)CSSC[C@@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(O)=O)Cc3ccc(O)cc3)=O)CCCNC(N)=N)=O)Cc4ccccc4)=O)CO)=O)CC(N)=O)=O)NC(CNC([C@@H](NC(CNC([C@@H](NC([C@@H](NC([C@@H](NC(CNC1=O)=O)C)=O)CCC(N)=O)=O)CO)=O)=O)CC(C)C)=O)=O)=O)Cc5ccccc5)=O)=O)=O)CCCNC(N)=N)=O)CCSC)=O)CC(O)=O)=O)CCCNC(N)=N)=O)C

Ularitide is a32-amino acid peptide derived from (95-126 residues) of ANP PROHORMONE (1-126 residues); not biologically inactivated by a peptidase from dog kidney cortex membranes.

Reference

1: Anker SD, Ponikowski P, Mitrovic V, Peacock WF, Filippatos G. Ularitide for the treatment of acute decompensated heart failure: from preclinical to clinical studies. Eur Heart J. 2015 Mar 21;36(12):715-23. doi: 10.1093/eurheartj/ehu484. Epub 2015 Feb 10. Review. PubMed PMID: 25670819; PubMed Central PMCID: PMC4368857.
2: Emani S, Meyer M, Palm D, Holzmeister J, Haas GJ. Ularitide: a natriuretic peptide candidate for the treatment of acutely decompensated heart failure. Future Cardiol. 2015 Sep;11(5):531-46. doi: 10.2217/fca.15.53. Epub 2015 Aug 17. Review. PubMed PMID: 26278236.
3: Kumar VA, Viau D, Levy P. New Drugs You Are Going to Read About: Serelaxin, Ularitide, TRV027. Curr Emerg Hosp Med Rep. 2015 May 1;3(2):66-73. PubMed PMID: 26236569; PubMed Central PMCID: PMC4518848.
4: Mitrovic V, Seferovic PM, Simeunovic D, Ristic AD, Miric M, Moiseyev VS, Kobalava Z, Nitsche K, Forssmann WG, Lüss H, Meyer M. Haemodynamic and clinical effects of ularitide in decompensated heart failure. Eur Heart J. 2006 Dec;27(23):2823-32. Epub 2006 Oct 30. PubMed PMID: 17074775.
5: Lüss H, Mitrovic V, Seferovic PM, Simeunovic D, Ristić AD, Moiseyev VS, Forssmann WG, Hamdy AM, Meyer M. Renal effects of ularitide in patients with decompensated heart failure. Am Heart J. 2008 Jun;155(6):1012.e1-8. doi: 10.1016/j.ahj.2008.02.011. PubMed PMID: 18513512.
6: Meyer M, Uberbacher HJ, Böhm E, Schöpe KB, Brett W, Forssmann WG. Ularitide: from renal natriuretic peptide to clinical trials. Curr Opin Nephrol Hypertens. 1996 Jul;5(4):364-8. Review. PubMed PMID: 8823536.
7: Meyer M, Pfarr E, Schirmer G, Uberbacher HJ, Schöpe K, Böhm E, Flüge T, Mentz P, Scigalla P, Forssmann WG. Therapeutic use of the natriuretic peptide ularitide in acute renal failure. Ren Fail. 1999 Jan;21(1):85-100. PubMed PMID: 10048120.
8: Korn C, Neidlein R, Strein K, Wilhelms OH. Synergistic effects of ularitide acetate with classical bronchorelaxants on guinea-pig tracheal smooth muscle. Arzneimittelforschung. 1998 May;48(5):475-81. PubMed PMID: 9638314.
9: Tran HA, Lin F, Greenberg BH. Potential new drug treatments for congestive heart failure. Expert Opin Investig Drugs. 2016 Jul;25(7):811-26. doi: 10.1080/13543784.2016.1181749. Epub 2016 May 17. Review. PubMed PMID: 27104862.
10: Greenberg B. Novel Therapies for Heart Failure　- Where Do They Stand? Circ J. 2016 Aug 25;80(9):1882-91. doi: 10.1253/circj.CJ-16-0742. Epub 2016 Aug 19. Review. PubMed PMID: 27545139.
11: Mitrovic V, Lüss H, Nitsche K, Forssmann K, Maronde E, Fricke K, Forssmann WG, Meyer M. Effects of the renal natriuretic peptide urodilatin (ularitide) in patients with decompensated chronic heart failure: a double-blind, placebo-controlled, ascending-dose trial. Am Heart J. 2005 Dec;150(6):1239. PubMed PMID: 16338265.
12: Raj L, Adhyaru B. An evidence-based review of recent advances in therapy for heart failure with reduced ejection fraction (HFrEF). Postgrad Med J. 2016 Dec;92(1094):726-734. doi: 10.1136/postgradmedj-2016-134378. Epub 2016 Oct 5. Review. PubMed PMID: 27708003.
13: Herbert MK, Ginzel S, Mühlschlegel S, Weis KH. Concomitant treatment with urodilatin (ularitide) does not improve renal function in patients with acute renal failure after major abdominal surgery–a randomized controlled trial. Wien Klin Wochenschr. 1999 Feb 26;111(4):141-7. PubMed PMID: 10192146.
14: Meyer M, Flüge T, Kruhøffer M, Forssmann WG. Basic aspects of vasorelaxant and bronchodilating peptides in clinical use: urodilatin (INN: Ularitide), VIP, and PACAP. Ann N Y Acad Sci. 1996 Dec 26;805:443-61; discussion 461-3. Review. PubMed PMID: 8993423.
15: Meyer M, Wiebe K, Wahlers T, Zenker D, Schulze FP, Michels P, Forssmann WG. Urodilatin (INN:ularitide) as a new drug for the therapy of acute renal failure following cardiac surgery. Clin Exp Pharmacol Physiol. 1997 May;24(5):374-6. PubMed PMID: 9143791.
16: Hanigan S, DiDomenico RJ. Emerging Therapies for Acute and Chronic Heart Failure: Hope or Hype? J Pharm Pract. 2016 Feb;29(1):46-57. doi: 10.1177/1933719115615877. Review. PubMed PMID: 26759311.
17: Kuse ER, Meyer M, Constantin R, Oldhafer K, Schlitt HJ, Schulz-Knappe P, Uberbacher HJ, Pichlmayr R, Forssmann WG. [Urodilatin (INN: ularitide). A new peptide in the treatment of acute kidney failure following liver transplantation]. Anaesthesist. 1996 Apr;45(4):351-8. German. PubMed PMID: 8702053.
18: Korn C, Neidlein R, Strein K, Wilhelms OH. Comparison of the effects of ularitide acetate and other bronchorelaxing substances on the thrombin-induced permeability raise of human endothelial cell monolayers. Arzneimittelforschung. 1998 Mar;48(3):251-8. PubMed PMID: 9553682.
19: Wiebe K, Meyer M, Wahlers T, Zenker D, Schulze F, Michels P, Dalichau H, Mohr FW, Borst H, Forssmann WG. Acute renal failure following cardiac surgery is reverted by administration of Urodilatin (INN: Ularitide). Eur J Med Res. 1996 Feb 22;1(5):259-65. PubMed PMID: 9374447.
20: Brenner P, Meyer M, Reichenspurner H, Meiser B, Müller R, Mentz P, Schulz-Knappe P, Uberbacher HJ, Kreuzer E, Uberführ P, et al. Significance of prophylactic urodilatin (INN: ularitide) infusion for the prevention of acute renal failure in patients after heart transplantation. Eur J Med Res. 1995 Dec 18;1(3):137-43. PubMed PMID: 9389675.