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Neuromedin U-25 (human)

* Please kindly note that our products are not to be used for therapeutic purposes and cannot be sold to patients.

Neuromedin U-25 (NMU-25) is a 25-amino acid neuropeptide found in CNS of humans, demonstrated to drive smooth muscle contraction and regulate blood pressure. In vivo study has shown that it regulates feeding, vasoconstriction, nociception, and bone remodeling and contributes to obesity, cancer and septic shock.

Category

Peptide Inhibitors

Catalog number

BAT-015262

CAS number

312306-89-1

Molecular Formula

C141H203N41O38

Molecular Weight

3080.37

Specification
Reference Reading

IUPAC Name

(4S)-5-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[(2S)-2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-5-carbamimidamido-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-carbamimidamido-1-[(2S)-2-[[(2S)-5-carbamimidamido-1-[[(2S)-1,4-diamino-1,4-dioxobutan-2-yl]amino]-1-oxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-hydroxy-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-phenylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylbutanoyl]amino]-3-carboxypropanoyl]amino]-4-carboxybutanoyl]amino]-5-oxopentanoic acid

Synonyms

NMU-25 (human); H-Phe-Arg-Val-Asp-Glu-Glu-Phe-Gln-Ser-Pro-Phe-Ala-Ser-Gln-Ser-Arg-Gly-Tyr-Phe-Leu-Phe-Arg-Pro-Arg-Asn-NH2; L-Aspartamide, L-phenylalanyl-L-arginyl-L-valyl-L-α-aspartyl-L-α-glutamyl-L-α-glutamyl-L-phenylalanyl-L-glutaminyl-L-seryl-L-prolyl-L-phenylalanyl-L-alanyl-L-seryl-L-glutaminyl-L-seryl-L-arginylglycyl-L-tyrosyl-L-phenylalanyl-L-leucyl-L-phenylalanyl-L-arginyl-L-prolyl-L-arginyl-

Appearance

White Lyophilized Powder

Purity

≥98%

Density

1.5±0.1 g/cm3

Sequence

FRVDEEFQSPFASQSRGYFLFRPRN-NH2

Storage

Store at -20°C

Solubility

Soluble in Acetic Acid

InChI

InChI=1S/C141H203N41O38/c1-74(2)61-94(125(208)173-98(65-80-33-17-9-18-34-80)128(211)169-92(40-24-58-158-141(153)154)136(219)181-59-25-41-104(181)133(216)168-86(38-22-56-156-139(149)150)118(201)170-93(114(146)197)68-108(145)189)171-129(212)99(66-81-35-19-10-20-36-81)174-126(209)95(67-82-43-45-83(186)46-44-82)161-109(190)70-159-117(200)85(37-21-55-155-138(147)148)163-132(215)102(72-184)178-121(204)88(47-51-106(143)187)167-131(214)101(71-183)177-115(198)76(5)160-124(207)96(63-78-29-13-7-14-30-78)175-134(217)105-42-26-60-182(105)137(220)103(73-185)179-122(205)89(48-52-107(144)188)165-127(210)97(64-79-31-15-8-16-32-79)172-120(203)91(50-54-111(193)194)164-119(202)90(49-53-110(191)192)166-130(213)100(69-112(195)196)176-135(218)113(75(3)4)180-123(206)87(39-23-57-157-140(151)152)162-116(199)84(142)62-77-27-11-6-12-28-77/h6-20,27-36,43-46,74-76,84-105,113,183-186H,21-26,37-42,47-73,142H2,1-5H3,(H2,143,187)(H2,144,188)(H2,145,189)(H2,146,197)(H,159,200)(H,160,207)(H,161,190)(H,162,199)(H,163,215)(H,164,202)(H,165,210)(H,166,213)(H,167,214)(H,168,216)(H,169,211)(H,170,201)(H,171,212)(H,172,203)(H,173,208)(H,174,209)(H,175,217)(H,176,218)(H,177,198)(H,178,204)(H,179,205)(H,180,206)(H,191,192)(H,193,194)(H,195,196)(H4,147,148,155)(H4,149,150,156)(H4,151,152,157)(H4,153,154,158)/t76-,84-,85-,86-,87-,88-,89-,90-,91-,92-,93-,94-,95-,96-,97-,98-,99-,100-,101-,102-,103-,104-,105-,113-/m0/s1

InChI Key

VXJPSOQJNUZHDN-YJFQKBDPSA-N

Canonical SMILES

CC(C)CC(C(=O)NC(CC1=CC=CC=C1)C(=O)NC(CCCNC(=N)N)C(=O)N2CCCC2C(=O)NC(CCCNC(=N)N)C(=O)NC(CC(=O)N)C(=O)N)NC(=O)C(CC3=CC=CC=C3)NC(=O)C(CC4=CC=C(C=C4)O)NC(=O)CNC(=O)C(CCCNC(=N)N)NC(=O)C(CO)NC(=O)C(CCC(=O)N)NC(=O)C(CO)NC(=O)C(C)NC(=O)C(CC5=CC=CC=C5)NC(=O)C6CCCN6C(=O)C(CO)NC(=O)C(CCC(=O)N)NC(=O)C(CC7=CC=CC=C7)NC(=O)C(CCC(=O)O)NC(=O)C(CCC(=O)O)NC(=O)C(CC(=O)O)NC(=O)C(C(C)C)NC(=O)C(CCCNC(=N)N)NC(=O)C(CC8=CC=CC=C8)N

1.Neuromedin U stimulates contraction of human long saphenous vein and gastrointestinal smooth muscle in vitro.

Jones NA1, Morton MF, Prendergast CE, Powell GL, Shankley NP, Hollingsworth SJ. Regul Pept. 2006 Sep 11;136(1-3):109-16. Epub 2006 Jun 19.

The neuropeptide Neuromedin U (NMU) stimulates smooth muscle contraction, and modulates local blood flow and adrenocortical function via two endogenous receptors, NMU1 and NMU2. Although its amino-acid sequence is highly conserved across species, the physiological effects of NMU are variable between species and little is known of its effects on human tissues. We have examined the contractile effects of NMU-25 on human smooth muscles of the gastrointestinal (GI) tract (ascending colon, gallbladder) and long saphenous vein (LSV) using in vitro organ bath bioassays. From LSV, ileum, gallbladder, caecum and colon, NMU receptor transcripts were amplified by RT-PCR and expression levels were determined by semi-quantitative scanning densitometry. NMU-25 produced a concentration-dependent, sustained contraction of isolated smooth muscle (p[A](50)+/-s.e.m., ascending colon, 8.93+/-0.18; gallbladder, 7.01+/-0.15; LSV, 8.67+/-0.09). NMU1 and NMU2 receptor transcription was detected in all tissues; transcription of both receptors was similar in gallbladder, but NMU1 receptor transcription was predominant in the sigmoid colon and LSV.

2.Expression and vasoconstrictor function of anorexigenic peptides neuromedin U-25 and S in the human cardiovascular system.

Mitchell JD1, Maguire JJ, Kuc RE, Davenport AP. Cardiovasc Res. 2009 Feb 1;81(2):353-61. doi: 10.1093/cvr/cvn302. Epub 2008 Nov 5.

AIMS: Neuromedin U-25 (NMU-25), a brain-gut peptide with anorexigenic actions, was paired with the G-protein-coupled receptors NMU1 and NMU2 in 2000. NMU-25 elicited a potent hypertensive effect in rats but little is known about its cardiovascular effects in humans. We examined the hypothesis that NMU fulfils the criteria for controlling vascular reactivity within the human cardiovascular system.

3.The neuromedin U-growth hormone secretagogue receptor 1b/neurotensin receptor 1 oncogenic signaling pathway as a therapeutic target for lung cancer.

Takahashi K1, Furukawa C, Takano A, Ishikawa N, Kato T, Hayama S, Suzuki C, Yasui W, Inai K, Sone S, Ito T, Nishimura H, Tsuchiya E, Nakamura Y, Daigo Y. Cancer Res. 2006 Oct 1;66(19):9408-19.

Using a genome-wide cDNA microarray to search for genes that were specifically up-regulated in non-small cell lung cancers (NSCLC), we identified an abundant expression of neuromedin U (NMU) in the great majority of lung cancers. Immunohistochemical analysis showed a significant association of NMU expression with poorer prognosis of patients with NSCLC. Treatment of NSCLC cells with short interfering RNA against NMU suppressed its expression and inhibited the growth of the cells; on the other hand, the induction of exogenous expression of NMU conferred growth-promoting activity and enhanced cell mobility in vitro. We found that two G protein-coupled receptors, growth hormone secretagogue receptor 1b and neurotensin receptor 1, were also overexpressed in NSCLC cells, and that a heterodimer complex of these receptors functioned as an NMU receptor. The NMU-receptor interaction subsequently induced the generation of a second messenger, cyclic AMP, to activate its downstream genes including transcription factors and cell cycle regulators.

4.ECL-cell histamine mobilization in conscious rats: effects of locally applied regulatory peptides, candidate neurotransmitters and inflammatory mediators.

Norlén P1, Bernsand M, Konagaya T, Håkanson R. Br J Pharmacol. 2001 Dec;134(8):1767-77.

1. The ECL cells control gastric acid secretion by mobilizing histamine in response to circulating gastrin. In addition, the ECL cells are thought to operate under nervous control and to be influenced by local inflammatory processes. 2. The purpose of the present study was to monitor histamine mobilization from ECL cells in conscious rats in response to locally applied regulatory peptides, candidate neurotransmitters and inflammatory mediators. 3. Microdialysis probes were implanted in the submucosa of the acid-producing part of the rat stomach. Three days later, the agents to be tested were administered via the microdialysis probe and their effects on basal (48 h fast) and stimulated (intravenous infusion of gastrin-17, 3 nmol kg(-1) h(-1)) mobilization of ECL-cell histamine was monitored by continuous measurement of histamine in the perfusate (radioimmunoassay). 4. Locally administered gastrin-17 and sulfated cholecystokinin-8 mobilized histamine as did pituitary adenylate cyclase-activating peptide-27, vasoactive intestinal peptide, peptide YY, met-enkephalin, endothelin and noradrenaline, adrenaline and isoprenaline.