Endogenous Metabolite

Research indicates that Phosphocreatine possesses neuroprotective and renoprotective potential. In terms of neuroprotection, Phosphocreatine (5-20 mM, 24 h) attenuates MGO (Methylglyoxal)-induced PC12 cell damage, inhibits apoptosis [3], and prevents the loss of mitochondrial membrane permeability [3]. Its mechanism of action involves normalizing mitochondrial function and reducing oxidative stress through the Akt-mediated Nrf2/HO-1 pathway [3]. Regarding renoprotection, Phosphocreatine (5-40 mM, 24 h) protects NRK-52E cells from MGO-induced kidney injury in a concentration-dependent manner [4], and its application at 10-40 mM for 4 h inhibits the production of renal oxidative stress metabolites [4].

In the context of DOX-induced cardiotoxicity, Phosphocreatine treatment (200 mg/kg, i.p., every other day for 7 weeks) attenuated oxidative stress and apoptosis, and rescued myocardial tissue from necroptosis [2]. Additionally, in a diabetic nephropathy model, Phosphocreatine (20-40 mg/kg, i.v., daily for 6 weeks) demonstrated renoprotective effects by preserving renal function in Sprague-Dawley rats [4].

[1]. Creatine: a dietary supplement and ergogenic aid. Nutr Rev. 1999 Feb;57(2):45-50.

[2]. Phosphocreatine attenuates doxorubicin-induced cardiotoxicity by inhibiting oxidative stress and activating TAK1 to promote myocardial survival in vivo and in vitro. Toxicology. 2021 Aug;460:152881.

[3]. Neuroprotective effect of phosphocreatine on oxidative stress and mitochondrial dysfunction induced apoptosis in vitro and in vivo: Involvement of dual PI3K/Akt and Nrf2/HO-1 pathways. Free Radic Biol Med. 2018 May 20;120:228-238.

[4]. Protection of diabetes-induced kidney injury by phosphocreatine via the regulation of ERK/Nrf2/HO-1 signaling pathway. Life Sci. 2020 Feb 1;242:117248.

Myocardial apoptosis and necroptosis are the main causes of doxorubicin (DOX)-induced cardiotoxicity and one of the important reasons limiting the clinical application of this drug. To date, the mechanism remains incompletely understood. The protective effect of creatine phosphate (PCr) in cardiac surgery and cardiology has been confirmed in numerous clinical trials. This study aimed to evaluate the protective effect of PCr against DOX-induced cardiotoxicity and explore its potential mechanism, particularly the transforming growth factor β-activated kinase 1 (TAK1)-mediated myocardial survival signaling pathway. Male Sprague-Dawley rats were used as an animal model, and patients were intraperitoneally injected with normal saline (NS), DOX (2 mg/kg), or DOX combined with PCr (200 mg/kg), respectively. Data showed that doxorubicin (DOX) significantly impaired cardiac function and structure, induced oxidative stress, Myocardial apoptosis and necroptosis, and significantly downregulated TAK1 expression levels; while intervention with creatine phosphate (PCr) significantly alleviated cardiac dysfunction, oxidative stress, Myocardial apoptosis and necroptosis, especially mitigating the decrease in TAK1 expression. In in vitro experiments, H9c2 cells were pretreated with PCr (0.5 mM), N-acetyl-L-cysteine (NAC, 0.5 mM), or 5Z-7-oxozeenol (5Z-7-Ox, 1 μM) for 1 hour, followed by DOX (1 μM) treatment for 24 hours. The results showed that inhibiting TAK1 further exacerbated DOX-induced apoptosis and necrotizing apoptosis in H9c2 cells, but had no effect on oxidative stress. PCr or NAC pretreatment enhanced antioxidant activity, reduced oxidative stress, and significantly alleviated DOX-induced apoptosis and necrotizing cell death in H9c2 cells. Consistent with in vivo results, PCr or NAC significantly inhibited DOX-induced decrease in TAK1 expression. In summary, DOX-induced oxidative stress inhibits TAK1 expression, leading to Myocardial apoptosis and necrotic cell death; while PCr intervention can enhance antioxidant activity, reduce oxidative stress, thereby activating the TAK1 signaling pathway, promoting Myocardial survival, and ultimately reducing DOX-induced cardiotoxicity. [2]

C4H10N3NA2O6P

273.09200334549

255

19333-65-4

Phosphocreatine disodium;922-32-7;Phosphocreatine;67-07-2;Sodium creatine phosphate dibasic tetrahydrate;71519-72-7;Phosphocreatine dipotassium;18838-38-5;67-07-2;19333-65-4;71519-72-7;922-32-7;

44134639

White to off-white solid powder

6

10

3

19

259

0

P(N=C(N)N(C)CC(=O)O)(=O)([O-])[O-].[Na+].[Na+].O

HUWYWJSJJDCZRQ-UHFFFAOYSA-L

InChI=1S/C4H10N3O5P.2Na.4H2O/c1-7(2-3(8)9)4(5)6-13(10,11)12;;;;;;/h2H2,1H3,(H,8,9)(H4,5,6,10,11,12);;;4*1H2/q;2*+1;;;;/p-2

disodium;2-[methyl-(N'-phosphonatocarbamimidoyl)amino]acetic acid;tetrahydrate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

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.)