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Davunetide

Alias: Davunetide AL 208 AL 108
Cat No.:V8388 Purity: ≥95%
Davunetide is an eight-amino acid (AA) polypeptide developed from activity-dependent neuro-protective (neuro-protection) protein (ADNP), a neurotrophic factor present in the mammalian central nervous system.
Davunetide
Davunetide Chemical Structure CAS No.: 211439-12-2
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
Davunetide is an eight-amino acid (AA) polypeptide developed from activity-dependent neuro-protective (neuro-protection) protein (ADNP), a neurotrophic factor present in the mammalian central nervous system. Davunetide has neuro-protective (neuro-protection), neurotrophic and cognitive protective properties. Davunetide is a microtubule-stabilizing peptide that interacts with neuron-specific βIII tubulin in vitro and stabilizes its activity. Davunetide penetrates the BBB (blood-brain barrier) and is non-toxic. Davunetide inhibits Aβ aggregation and Aβ-induced neurotoxicity.
Biological Activity I Assay Protocols (From Reference)
ln Vivo
In an intranasal davunetide (2 μg/kg) administered once daily for five days a week for sixteen weeks, a diabetic rat model demonstrated protection against problems of the central nervous system [3].
Animal Protocol
Animal/Disease Models: Male SD (SD (Sprague-Dawley)) rats (induced by intraperitoneal (ip) injection of streptozotocin (STZ)) [3]
Doses: 2 μg/kg
Route of Administration: Intranasal administration starting the day after STZ injection, Daily dosing, 5 days per week, for 16 weeks
Experimental Results: Impaired spatial memory in diabetic rats was observed in the water maze, manifested by an attenuated learning curve and worsened performance in the probe memory test. Davonidetide treatment Dramatically improved both measures.
References

[1]. NAP (davunetide) rescues neuronal dysfunction in a Drosophila model of tauopathy. Mol Psychiatry. 2013;18(7):834-842.

[2]. Davunetide improves spatial learning and memory in Alzheimer's disease-associated rats. Physiol Behav. 2017;174:67-73.

[3]. Davunetide (NAP) as a preventative treatment for central nervous system complications in a diabetes rat model. Neurobiol Dis. 2011;44(3):327-339.

Additional Infomation
Davunetide is an oligopeptide.
Davunetide has been used in trials studying the treatment of Progressive Nonfluent Aphasia, Progressive Supranuclear Palsy, Predicted Tauopathies, Including, Corticobasal Degeneration Syndrome, and Frontotemporal Dementia With Parkinsonism Linked to Chromosome 17. Davunetide is the first drug to improve memory performance by impacting the mechanisms that lead to physical damage in the brain caused by neurofibrillary tangles, one of the two established pathological hallmarks that are common to amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD). Davunetide is derived from a naturally occurring neuroprotective brain protein known as activity dependent neuroprotective protein.
Mechanism of Action
Davunetide interacts with microtubules 1) preventing the formation of neurofibrillary tanges and protecting the network from a 'death signal' or 2) repairing the network if the brain cell death process has already begun. The restoration of the microtubule network explains the results shown in treated animals which have improved cognitive performance compared to untreated groups.
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C36H60N10O12
Molecular Weight
824.93
Exact Mass
824.439
CAS #
211439-12-2
Related CAS #
211439-12-2;
PubChem CID
9832404
Appearance
White to off-white solid powder
Density
1.3±0.1 g/cm3
Boiling Point
1333.8±65.0 °C at 760 mmHg
Flash Point
760.5±34.3 °C
Vapour Pressure
0.0±0.6 mmHg at 25°C
Index of Refraction
1.566
LogP
-1.78
Hydrogen Bond Donor Count
10
Hydrogen Bond Acceptor Count
13
Rotatable Bond Count
22
Heavy Atom Count
58
Complexity
1560
Defined Atom Stereocenter Count
9
SMILES
CC[C@@H]([C@H](NC([C@@H](NC([C@@H](NC([C@@H]1CCCN1C([C@@H](NC([C@@H](N)CC(N)=O)=O)C)=O)=O)C(C)C)=O)CO)=O)C(N2CCC[C@H]2C(N[C@H](C(O)=O)CCC(N)=O)=O)=O)C
InChi Key
DWLTUUXCVGVRAV-XWRHUKJGSA-N
InChi Code
InChI=1S/C36H60N10O12/c1-6-18(4)28(35(56)46-14-8-9-23(46)31(52)41-21(36(57)58)11-12-25(38)48)44-30(51)22(16-47)42-33(54)27(17(2)3)43-32(53)24-10-7-13-45(24)34(55)19(5)40-29(50)20(37)15-26(39)49/h17-24,27-28,47H,6-16,37H2,1-5H3,(H2,38,48)(H2,39,49)(H,40,50)(H,41,52)(H,42,54)(H,43,53)(H,44,51)(H,57,58)/t18-,19-,20-,21-,22-,23-,24-,27-,28-/m0/s1
Chemical Name
(2S)-5-amino-2-[[(2S)-1-[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2,4-diamino-4-oxobutanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]-3-hydroxypropanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoic acid
Synonyms
Davunetide AL 208 AL 108
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, avoid exposure to moisture.
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)
DMSO : ~125 mg/mL (~151.53 mM)
H2O : ~100 mg/mL (~121.22 mM)
Solubility (In Vivo)
Solubility in Formulation 1: ≥ 2.08 mg/mL (2.52 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
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.

 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 1.2122 mL 6.0611 mL 12.1222 mL
5 mM 0.2424 mL 1.2122 mL 2.4244 mL
10 mM 0.1212 mL 0.6061 mL 1.2122 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.

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Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
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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.
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Clinical Trial Information
NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT01056965 COMPLETED Drug: davunetide (AL-108, NAP)
Drug: Placebo nasal spray
Corticobasal Degeneration Syndrome
Frontotemporal Dementia With Parkinsonism Linked to Chromosome 17
Predicted Tauopathies, Including
University of California, San Francisco 2010-01 Phase 1
NCT01110720 COMPLETED Drug: Davunetide
Drug: Placebo
Progressive Supranuclear Palsy Allon Therapeutics 2010-10 Phase 2
Phase 3
NCT00505765 COMPLETEDWITH RESULTS Drug: AL-108
Drug: AL-108
Drug: Placebo
Drug: Placebo
Schizophrenia University of California, Los Angeles 2007-07 Phase 2
NCT00404014 COMPLETED Drug: AL-208
Drug: Placebo
Mild Cognitive Impairment Allon Therapeutics 2006-08 Phase 2
NCT00422981 COMPLETED Drug: AL-108
Drug: AL-108
Drug: Placebo
Mild Cognitive Impairment, So Stated Allon Therapeutics 2007-01 Phase 2
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