Methionine-brain peptide (MENK) is an endogenous neuropeptide that is essential to the immunological and neuroendocrine systems. It is believed that MENK exhibits immunomodulatory properties. MENK can also alter the tumor microenvironment by binding to opioid absorption on or inside cancer cells and interacting with immune and cancer cells. Each of these possesses biological importance and the ability to manipulate cancer immunity mechanistically. Moreover, they disclose the connection between the immune system and the intestines [1].

Absorption, Distribution and Excretion
Metenkefalin reaches a Cmax of 1266.14pg/mL, with a Tmax of 0.16h, and an AUC of 360.64pg\*h/mL.

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Biological Half-Life
The half life of metenkefalin is 4.2-39 minutes.

[1]. Methionine enkephalin, its role in immunoregulation and cancer therapy. Int Immunopharmacol. 2016 Feb 23. pii: S1567-5769(16)30050-9.

Metenkefalin is an endogenous opioid and beta-endorphin. It has been shown to reduce chromosomal abberations in patients with multiple sclerosis. Metenkefalin, along with [tridecactide], are under investigation as an immunomodulatory therapy for moderate to severe COVID-19.
MET-enkephalin has been reported in Mytilus edulis and Apis cerana with data available.
Metenkefalin is a synthetic form of the naturally occurring, endogenous opioid peptide, metenkephalin, and agonist of the zeta- and delta-opioid receptor and, to a lesser extent the mu-opioid receptor, with potential analgesic, neuromodulatory, immunomodulatory, anti-inflammatory, antinociceptive/analgesic, antidepressant, and gastrointestinal (GI) motility modulating activities. Upon administration, metenkefalin mimics its endogenous ligand and targets, binds to and activates the opioid receptors. This leads to an analgesic effect, inhibits neuropathic pain, and inhibits GI muscle contractility. Binding to the opioid growth factor receptor (OGFR; zeta-opioid receptor), enhances tissue growth and regeneration. In addition, activation of delta-opioid receptors located on a variety of immune cells may modulate the inflammatory immune response. This may inhibit the secretion of pro-inflammatory cytokines and the proliferation of leukocytes.
Opioid Growth Factor is an endogenous pentapeptide with potential antineoplastic and antiangiogenic activities. Opioid growth factor (OGF) binds to and activates the OGF receptor, present on some tumor cells and vascular cells, thereby inhibiting tumor cell proliferation and angiogenesis. (NCI05)
One of the endogenous pentapeptides with morphine-like activity. It differs from LEU-ENKEPHALIN by the amino acid METHIONINE in position 5. Its first four amino acid sequence is identical to the tetrapeptide sequence at the N-terminal of BETA-ENDORPHIN.

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Drug Indication
Metenkefalin is indicated in Bosnia for the treatment of relapsing-remitting multiple sclerosis.

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Mechanism of Action
Metenkefalin is an agonist of µ and δ opioid receptors. It also causes immunostimulation at low doses and immunosuppression at higher doses. Metenkefalin can also inhibit the production of aldosterone, deoxycorticosterone, and corticosterone. Unfortunately, the mechanisms by which these effects occur have not been well described in the literature.

C27H35N5O7S

573.665

573.226

58569-55-4

443363

White to off-white solid powder

1.324 g/cm3

1052.9ºC at 760 mmHg

590.6ºC

1.608

1.808

7

9

16

40

847

3

CSCC[C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)CNC(=O)CNC(=O)[C@H](CC2=CC=C(C=C2)O)N

YFGBQHOOROIVKG-FKBYEOEOSA-N

InChI=1S/C27H35N5O7S/c1-40-12-11-21(27(38)39)32-26(37)22(14-17-5-3-2-4-6-17)31-24(35)16-29-23(34)15-30-25(36)20(28)13-18-7-9-19(33)10-8-18/h2-10,20-22,33H,11-16,28H2,1H3,(H,29,34)(H,30,36)(H,31,35)(H,32,37)(H,38,39)/t20-,21-,22-/m0/s1

(2S)-2-[[(2S)-2-[[2-[[2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]acetyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-4-methylsulfanylbutanoic acid

Enkephalin methionine; CCRIS 4225; (Met5)-enkephalin

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ≥ 40 mg/mL (~69.73 mM)
H2O : ~6.67 mg/mL (~11.63 mM)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)