Davunetide | AL-208 | AL-108 | CAS#211439-12-2

MedKoo Cat#: 524941 | Name: Davunetide

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Davunetide is an eight amino acid peptide (NAPVSIPQ) that has been shown to provide potent neuroprotection, in vitro and in vivo. Davunetide has been shown to increase memory scores in patients suffering from amnestic mild cognitive impairment, a precursor to Alzheimer's disease and to enhance functional daily behaviors in schizophrenia patients.

Chemical Structure

Davunetide

CAS#211439-12-2 (free base)

Theoretical Analysis

MedKoo Cat#: 524941

Name: Davunetide

CAS#: 211439-12-2 (free base)

Chemical Formula: C36H60N10O12

Exact Mass: 824.4392

Molecular Weight: 824.93

Elemental Analysis: C, 52.42; H, 7.33; N, 16.98; O, 23.27

Price and Availability

Size	Price	Availability	Quantity
10mg	USD 350.00	2 Weeks
25mg	USD 650.00	2 Weeks

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Related CAS #

211439-12-2 (free base) Davunetide acetate

Synonym

Davunetide; AL108; AL 108; AL-108; AL208; AL 208; AL-208; H2N-L-Asn-L-Ala-L-Pro-L-Val-L-Ser-L-Ile-L-Pro-L-Gln-COOH; NAP (peptide); NAPVSIPQ

IUPAC/Chemical Name

L-asparaginyl-L-alanyl-L-prolyl-L-valyl-L-seryl-L-isoleucyl-L-prolyl-L-glutamine

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

SMILES Code

CC[C@H](C)[C@@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](C(C)C)NC(=O)[C@@H]2CCCN2C(=O)[C@H](C)NC(=O)[C@H](CC(=O)N)N

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

Davunetide is a highly potent active component of activity-dependent neuroprotective protein (ADNP) that prevents β-amyloid aggregation, reduces hyperphosphorylated tau levels, and increases tau-microtubule interactions.

In vitro activity:

To examine the mechanisms by which the A53T α-synuclein-induced impairment of mitochondrial trafficking in the neuronally differentiated SH-SY5Y cells, SH-SY5Y cell cultures were treated with NAP since it has been shown to restore microtubule integrity. Adding NAP, indeed, appeared to completely restore retrograde as well as anterograde mitochondria trafficking in the A53T αsynuclein expressing SH-SY5Y derived cells (Fig. 4). Although both motor proteins, dynein and kinesin, have clear structural distinctions and wander across the microtubule surface with different speed, step sizes and in opposite directions, apparently the A53T α-synuclein-induced microtubules destruction, restorable by NAP, affects the interaction between the motor proteins and the microtubules in a similar mode. Adding NAP to the culture also completely annihilated the ROS increase observed in all α-synuclein expressing cell lines (Fig. 5b, c). Reference: Exp Brain Res. 2017 Mar;235(3):731-742. https://pubmed.ncbi.nlm.nih.gov/27866262/

In vivo activity:

To further characterize the neuroprotective roles of davunetide and its possible mechanism, the present study investigated the effects of davunetide on Aβ1-42-induced impairments in spatial memory, synaptic plasticity and hippocampal AKT level. In Morris water maze (MWM) test, bilateral intrahippocampal injection of Aβ1-42 significantly increased escape latency and decreased target quadrant swimming time of rats, while three weeks of intranasal application of davunetide reversed the Aβ1-42-induced learning deficits and memory loss in a dose-dependent manner. In Morris water maze (MWM) test, davunetide effectively blocked the suppression of LTP, without affecting paired-pulse facilitation (PPF). Western blotting experiments showed a significant decrease in the level of hippocampal p-AKT (Ser473), not total AKT, in Aβ1-42 only group, which was mostly antagonized by davunetide treatment. These findings demonstrate that davunetide, probably by enhancing PI3K/AKT pathway, plays an important positive role in attenuating Aβ1-42-induced impairments in spatial memory and synaptic plasticity, suggesting that davunetide could be an effective therapeutic candidate for the prevention and treatment of neurodegenerative disease such as AD. Reference: Physiol Behav. 2017 May 15;174:67-73. https://pubmed.ncbi.nlm.nih.gov/28257938/

	Solvent	mg/mL	mM
Solubility
	DMSO	1.0	1.21

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 824.93 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Melo TQ, van Zomeren KC, Ferrari MF, Boddeke HW, Copray JC. Impairment of mitochondria dynamics by human A53T αsynuclein and rescue by NAP (davunetide) in a cell model for Parkinson's disease. Exp Brain Res. 2017 Mar;235(3):731-742. doi: 10.1007/s00221-016-4836-9. Epub 2016 Nov 19. PMID: 27866262; PMCID: PMC5315729. 2. D'Amico AG, Scuderi S, Maugeri G, Cavallaro S, Drago F, D'Agata V. NAP reduces murine microvascular endothelial cells proliferation induced by hyperglycemia. J Mol Neurosci. 2014 Nov;54(3):405-13. doi: 10.1007/s12031-014-0335-2. Epub 2014 May 30. PMID: 24874579. 3. Quraishe S, Cowan CM, Mudher A. NAP (davunetide) rescues neuronal dysfunction in a Drosophila model of tauopathy. Mol Psychiatry. 2013 Jul;18(7):834-42. doi: 10.1038/mp.2013.32. Epub 2013 Apr 16. PMID: 23587881; PMCID: PMC3690421 4. Zhang J, Wei SY, Yuan L, Kong LL, Zhang SX, Wang ZJ, Wu MN, Qi JS. Davunetide improves spatial learning and memory in Alzheimer's disease-associated rats. Physiol Behav. 2017 May 15;174:67-73. doi: 10.1016/j.physbeh.2017.02.038. Epub 2017 Feb 28. PMID: 28257938.

In vitro protocol:

In vivo protocol:

1. Quraishe S, Cowan CM, Mudher A. NAP (davunetide) rescues neuronal dysfunction in a Drosophila model of tauopathy. Mol Psychiatry. 2013 Jul;18(7):834-42. doi: 10.1038/mp.2013.32. Epub 2013 Apr 16. PMID: 23587881; PMCID: PMC3690421. 2. Zhang J, Wei SY, Yuan L, Kong LL, Zhang SX, Wang ZJ, Wu MN, Qi JS. Davunetide improves spatial learning and memory in Alzheimer's disease-associated rats. Physiol Behav. 2017 May 15;174:67-73. doi: 10.1016/j.physbeh.2017.02.038. Epub 2017 Feb 28. PMID: 28257938.

1: Morimoto BH, Fox AW, Stewart AJ, Gold M. Davunetide: a review of safety and efficacy data with a focus on neurodegenerative diseases. Expert Rev Clin Pharmacol. 2013 Sep;6(5):483-502. doi: 10.1586/17512433.2013.827403. Epub 2013 Aug 24. PMID: 23971871. 2: Magen I, Gozes I. Davunetide: Peptide therapeutic in neurological disorders. Curr Med Chem. 2014;21(23):2591-8. doi: 10.2174/0929867321666140217124945. PMID: 24533805. 3: Gozes I. NAP (davunetide) provides functional and structural neuroprotection. Curr Pharm Des. 2011;17(10):1040-4. doi: 10.2174/138161211795589373. PMID: 21524250. 4: Gozes I. Microtubules (tau) as an emerging therapeutic target: NAP (davunetide). Curr Pharm Des. 2011;17(31):3413-7. doi: 10.2174/138161211798072553. PMID: 21902667. 5: Zhang J, Wei SY, Yuan L, Kong LL, Zhang SX, Wang ZJ, Wu MN, Qi JS. Davunetide improves spatial learning and memory in Alzheimer's disease-associated rats. Physiol Behav. 2017 May 15;174:67-73. doi: 10.1016/j.physbeh.2017.02.038. Epub 2017 Feb 28. PMID: 28257938. 6: Magen I, Gozes I. Microtubule-stabilizing peptides and small molecules protecting axonal transport and brain function: focus on davunetide (NAP). Neuropeptides. 2013 Dec;47(6):489-95. doi: 10.1016/j.npep.2013.10.011. Epub 2013 Oct 24. PMID: 24210139. 7: Boxer AL, Lang AE, Grossman M, Knopman DS, Miller BL, Schneider LS, Doody RS, Lees A, Golbe LI, Williams DR, Corvol JC, Ludolph A, Burn D, Lorenzl S, Litvan I, Roberson ED, Höglinger GU, Koestler M, Jack CR Jr, Van Deerlin V, Randolph C, Lobach IV, Heuer HW, Gozes I, Parker L, Whitaker S, Hirman J, Stewart AJ, Gold M, Morimoto BH; AL-108-231 Investigators. Davunetide in patients with progressive supranuclear palsy: a randomised, double-blind, placebo-controlled phase 2/3 trial. Lancet Neurol. 2014 Jul;13(7):676-85. doi: 10.1016/S1474-4422(14)70088-2. Epub 2014 May 27. PMID: 24873720; PMCID: PMC4129545. 8: Gozes I. Microtubules, schizophrenia and cognitive behavior: preclinical development of davunetide (NAP) as a peptide-drug candidate. Peptides. 2011 Feb;32(2):428-31. doi: 10.1016/j.peptides.2010.10.030. Epub 2010 Nov 2. PMID: 21050875. 9: Jarskog LF, Dong Z, Kangarlu A, Colibazzi T, Girgis RR, Kegeles LS, Barch DM, Buchanan RW, Csernansky JG, Goff DC, Harms MP, Javitt DC, Keefe RS, McEvoy JP, McMahon RP, Marder SR, Peterson BS, Lieberman JA. Effects of davunetide on N-acetylaspartate and choline in dorsolateral prefrontal cortex in patients with schizophrenia. Neuropsychopharmacology. 2013 Jun;38(7):1245-52. doi: 10.1038/npp.2013.23. Epub 2013 Jan 16. PMID: 23325325; PMCID: PMC3656368. 10: Shiryaev N, Pikman R, Giladi E, Gozes I. Protection against tauopathy by the drug candidates NAP (davunetide) and D-SAL: biochemical, cellular and behavioral aspects. Curr Pharm Des. 2011;17(25):2603-12. doi: 10.2174/138161211797416093. PMID: 21728979. 11: Çakici N, van Beveren NJM, Judge-Hundal G, Koola MM, Sommer IEC. An update on the efficacy of anti-inflammatory agents for patients with schizophrenia: a meta-analysis. Psychol Med. 2019 Oct;49(14):2307-2319. doi: 10.1017/S0033291719001995. Epub 2019 Aug 23. PMID: 31439071; PMCID: PMC6763537. 12: Bakota L, Brandt R. Tau Biology and Tau-Directed Therapies for Alzheimer's Disease. Drugs. 2016 Mar;76(3):301-13. doi: 10.1007/s40265-015-0529-0. PMID: 26729186; PMCID: PMC4757605. 13: Javitt DC, Buchanan RW, Keefe RS, Kern R, McMahon RP, Green MF, Lieberman J, Goff DC, Csernansky JG, McEvoy JP, Jarskog F, Seidman LJ, Gold JM, Kimhy D, Nolan KS, Barch DS, Ball MP, Robinson J, Marder SR. Effect of the neuroprotective peptide davunetide (AL-108) on cognition and functional capacity in schizophrenia. Schizophr Res. 2012 Apr;136(1-3):25-31. doi: 10.1016/j.schres.2011.11.001. Epub 2011 Dec 12. PMID: 22169248. 14: Scuderi S, D'Amico AG, Castorina A, Federico C, Marrazzo G, Drago F, Bucolo C, D'Agata V. Davunetide (NAP) protects the retina against early diabetic injury by reducing apoptotic death. J Mol Neurosci. 2014 Nov;54(3):395-404. doi: 10.1007/s12031-014-0244-4. Epub 2014 Feb 2. PMID: 24488575. 15: Ivashko-Pachima Y, Maor-Nof M, Gozes I. NAP (davunetide) preferential interaction with dynamic 3-repeat Tau explains differential protection in selected tauopathies. PLoS One. 2019 Mar 13;14(3):e0213666. doi: 10.1371/journal.pone.0213666. PMID: 30865715; PMCID: PMC6415897. 16: Gozes I, Shazman S. A novel davunetide (NAPVSIPQQ to NAPVSIPQE) point mutation in activity-dependent neuroprotective protein (ADNP) causes a mild developmental syndrome. Eur J Neurosci. 2023 Jul;58(2):2641-2652. doi: 10.1111/ejn.15920. Epub 2023 Feb 9. PMID: 36669790. 17: Gold M, Lorenzl S, Stewart AJ, Morimoto BH, Williams DR, Gozes I. Critical appraisal of the role of davunetide in the treatment of progressive supranuclear palsy. Neuropsychiatr Dis Treat. 2012;8:85-93. doi: 10.2147/NDT.S12518. Epub 2012 Feb 9. PMID: 22347799; PMCID: PMC3280109. 18: Merenlender-Wagner A, Pikman R, Giladi E, Andrieux A, Gozes I. NAP (davunetide) enhances cognitive behavior in the STOP heterozygous mouse--a microtubule-deficient model of schizophrenia. Peptides. 2010 Jul;31(7):1368-73. doi: 10.1016/j.peptides.2010.04.011. Epub 2010 Apr 22. PMID: 20417241. 19: Quraishe S, Cowan CM, Mudher A. NAP (davunetide) rescues neuronal dysfunction in a Drosophila model of tauopathy. Mol Psychiatry. 2013 Jul;18(7):834-42. doi: 10.1038/mp.2013.32. Epub 2013 Apr 16. PMID: 23587881; PMCID: PMC3690421. 20: Idan-Feldman A, Schirer Y, Polyzoidou E, Touloumi O, Lagoudaki R, Grigoriadis NC, Gozes I. Davunetide (NAP) as a preventative treatment for central nervous system complications in a diabetes rat model. Neurobiol Dis. 2011 Dec;44(3):327-39. doi: 10.1016/j.nbd.2011.06.020. Epub 2011 Jul 27. PMID: 21827858.