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GM-608

Alias: GM-603; GM-602; GM-604
Cat No.:V21697 Purity: ≥98%
Alirinetide (GM604) is an oligopeptide containing 6 amino acid (AA)s.
GM-608
GM-608 Chemical Structure CAS No.: 725715-18-4
Product category: New1
This product is for research use only, not for human use. We do not sell to patients.
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Product Description
Alirinetide (GM604) is an oligopeptide containing 6 amino acid (AA)s. Alirinetide penetrates the BBB (blood-brain barrier) and may be utilized in the research/study of a variety of neurodegenerative diseases.
GM-608 (also known as Alirinetide, GM604) is an oligopeptide containing 6 amino acids. It penetrates the blood-brain barrier (BBB) and may be utilized in the research and study of a variety of neurodegenerative diseases. GM-608 has been investigated for the treatment of amyotrophic lateral sclerosis (ALS) and ischemic stroke. It is a synthetic peptide compound designed to interact with specific molecular targets involved in neurodegenerative processes and cellular stress responses. The compound has been studied for its neuroprotective and anti-inflammatory effects. Its ability to cross the BBB makes it a promising candidate for the treatment of central nervous system disorders. GM-608 is used in research to study the mechanisms of neurodegeneration and to develop new therapeutic strategies for ALS, stroke, and other neurological conditions.
Biological Activity I Assay Protocols (From Reference)
Targets
Neurodegenerative processes and cellular stress responses; specific molecular targets are not extensively characterized.
ln Vitro
Alirinetide (GM604) inhibits the death of SH-SY5Y cells 0.1–10 mg/mL for 24 hours [1]. In SH-SY5Y cells, alidinetide (48 h) primarily inhibits genes linked to Parkinson's disease, which are primarily associated with respiratory chain and mitochondrial protein complexes [1].
GM-608 (Alirinetide, GM604) is an oligopeptide containing 6 amino acids. It penetrates the blood-brain barrier (BBB) and may be utilized in the research and study of a variety of neurodegenerative diseases. The compound has been investigated for the treatment of amyotrophic lateral sclerosis (ALS) and ischemic stroke. Specific IC50 or EC50 values for target engagement are not extensively detailed in publicly available literature. The compound is designed to interact with specific molecular targets involved in neurodegenerative processes and cellular stress responses.
ln Vivo
In a 6-OHDA mouse model, incadrinetide (GM604) (0–20 mg/kg; intravenously; twice daily for 5 days) improves histological, biochemical, and behavioral features [1].
In vivo efficacy of GM-608 has been studied in animal models of amyotrophic lateral sclerosis (ALS) and ischemic stroke. As a neuroprotective agent, it has been shown to reduce neuronal damage and improve functional outcomes in these models. The compound's ability to penetrate the BBB is a key feature for its efficacy in CNS disorders. Specific dosing regimens and detailed efficacy data are available in the primary literature but not extensively detailed in public search results.
Enzyme Assay
GM-608 is a synthetic peptide. Its biological activity is assessed using in vitro cell-based assays in neuronal cell cultures. Cells are treated with GM-608 at various concentrations (typically 0.001-100 µM) and subjected to stress conditions (e.g., oxidative stress, excitotoxicity). Neuroprotection is assessed by measuring cell viability, neuronal survival, and apoptotic markers. Anti-inflammatory effects are assessed by measuring cytokine production. BBB penetration is assessed using in vitro BBB models or in vivo studies.
Cell Assay
Cell Viability Assay[1]
Cell Types: SH-SY5Y Cell
Tested Concentrations: 0.1, 1 or 10 mg/mL
Incubation Duration: 24 hrs (hours)
Experimental Results: Result in dose-dependent rescue of cell survival, with complete restoration of cell viability at the highest dose (10 mg /ml).
Cellular activity is evaluated in neuronal cell cultures (e.g., primary neurons, neuroblastoma cell lines). Cells are treated with GM-608 at various concentrations (typically 0.001-100 µM) for appropriate time periods. Cell viability is measured by MTT or calcein-AM staining. Apoptosis is measured by caspase-3/7 activation or Annexin V staining. Oxidative stress is measured by assessing ROS levels. Inflammatory cytokine production is measured by ELISA. Neurite outgrowth may be assessed in neuronal differentiation models.
Animal Protocol
Animal/Disease Models: C57BL/6 mouse, 6-hydroxydopamine (6-OHDA) mouse model [1]
Doses: 0, 1, 5, 10 or 20 mg/kg
Route of Administration: intravenous (iv) (iv)injection, twice (two times) daily, continuous 5-day
Experimental Results: Almost complete abrogation of the highest dose of 6-OHDA improved motor performance, increased the number of TH-positive neurons in the substantia nigra, and increased dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid in the brain (HVA) level.
In vivo efficacy is studied in animal models of amyotrophic lateral sclerosis (ALS) (e.g., SOD1-G93A transgenic mice) and ischemic stroke (e.g., middle cerebral artery occlusion model). GM-608 is administered via various routes (intravenous, intraperitoneal) at doses determined from pharmacokinetic and tolerability studies. Neurological function is assessed using behavioral tests (e.g., rotarod, grip strength, open field). Infarct size is measured in stroke models. Motor neuron survival is assessed in ALS models. Inflammatory markers are measured in brain tissue.
ADME/Pharmacokinetics
GM-608 (Alirinetide, GM604) has a molecular formula of C36H54N12O9 and a molecular weight of 798.89 g/mol. CAS Number: 725715-18-4. Appearance: Typically exists as solid at room temperature. Synonyms: GM-603; GM-602; GM-604. The compound is an oligopeptide. Storage: store at -20°C for long-term stability. It is soluble in DMSO and water.
Toxicity/Toxicokinetics
Specific toxicological data for GM-608 are not extensively published. As a research peptide, it should be handled with standard laboratory safety precautions. The compound is for research use only and not for human therapeutic applications without appropriate regulatory approval. Standard laboratory safety practices should be followed, including the use of personal protective equipment and adequate ventilation.
References

[1]. GM604 for Parkinson's Disease treatment: Pre-clinical findings and results from a pilot placebo-controlled trial. F1000Research, 2017, 6.

Additional Infomation
GM-608 (Alirinetide, GM604) is a research tool compound for studying neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and ischemic stroke. It is not approved for clinical use. The compound is an oligopeptide that penetrates the blood-brain barrier (BBB) and may be utilized in the research and study of a variety of neurodegenerative diseases. GM-608 is designed to interact with specific molecular targets involved in neurodegenerative processes and cellular stress responses. Its neuroprotective and anti-inflammatory properties make it a valuable tool for understanding the mechanisms of neurodegeneration and for developing new therapeutic strategies for CNS disorders.
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C36H54N12O9
Molecular Weight
798.889
Exact Mass
798.41
CAS #
725715-18-4
PubChem CID
9875671
Appearance
Typically exists as solid at room temperature
LogP
-4.9
Hydrogen Bond Donor Count
13
Hydrogen Bond Acceptor Count
12
Rotatable Bond Count
24
Heavy Atom Count
57
Complexity
1380
Defined Atom Stereocenter Count
6
SMILES
C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CO)NC(=O)[C@H](CC2=CC=CC=C2)N
InChi Key
WVPOPWDCSFQEBI-HJJAOGADSA-N
InChi Code
InChI=1S/C36H54N12O9/c1-20(29(51)46-26(34(56)57)10-6-16-43-36(40)41)44-32(54)27(18-22-11-13-23(50)14-12-22)47-31(53)25(9-5-15-42-35(38)39)45-33(55)28(19-49)48-30(52)24(37)17-21-7-3-2-4-8-21/h2-4,7-8,11-14,20,24-28,49-50H,5-6,9-10,15-19,37H2,1H3,(H,44,54)(H,45,55)(H,46,51)(H,47,53)(H,48,52)(H,56,57)(H4,38,39,42)(H4,40,41,43)/t20-,24-,25-,26-,27-,28-/m0/s1
Chemical Name
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-phenylpropanoyl]amino]-3-hydroxypropanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid
Synonyms
GM-603; GM-602; GM-604
HS Tariff Code
2934.99.9001
Storage

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 (e.g. under nitrogen), avoid exposure to moisture and light.
Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
H2O : ~100 mg/mL (~125.17 mM)
Solubility (In Vivo)
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.

Injection Formulations
(e.g. IP/IV/IM/SC)
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 : PEG300Tween 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 : PEG300Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH 400 μLPEG300 50 μL Tween 80 450 μL Saline)


Oral Formulations
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


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.

 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 1.2517 mL 6.2587 mL 12.5174 mL
5 mM 0.2503 mL 1.2517 mL 2.5035 mL
10 mM 0.1252 mL 0.6259 mL 1.2517 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

Calculator

Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

  • Calculate the Mass of a compound required to prepare a solution of known volume and concentration
  • Calculate the Volume of solution required to dissolve a compound of known mass to a desired concentration
  • Calculate the Concentration of a solution resulting from a known mass of compound in a specific volume
An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
  • Enter 350.26 in the Molecular Weight (MW) box
  • Enter 10 in the Concentration box and choose the correct unit (mM)
  • Enter 5 in the Volume box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
  • Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
  • Enter 25 into the Concentration (End) box and select the correct unit (mM)
  • Enter 25 into the Volume (End) box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box
g/mol

Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:
  • To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.
Definitions of molecular mass, molecular weight, molar mass and molar weight:
  • Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
  • Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.
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Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

  • Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
  • Click the “Calculate” button
  • The answer appears in the Volume (to add to vial) box
In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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Calculation results

Working concentration mg/mL;

Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.

(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
             (2) Be sure to add the solvent(s) in order.

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