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MedKoo Cat#: 328031 | Name: Posiphen
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Description:

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

Posiphen, also known as R-phenserine or (-)-Phenserine, is a selective, non-competitive inhibitor of acetylcholinesterase (AChE). (-)-Phenserine produces rapid, potent, and long-lasting AChE inhibition, in vivo. (-)-Phenserine attenuates soman-induced neuropathology. Posiphen is seen to reduce glutamate-mediated neuronal loss in co-cultures of primary cortical cells and microglia.

Chemical Structure

Posiphen
Posiphen
CAS#116839-68-0 (free base)

Theoretical Analysis

MedKoo Cat#: 328031

Name: Posiphen

CAS#: 116839-68-0 (free base)

Chemical Formula: C20H23N3O2

Exact Mass: 337.1790

Molecular Weight: 337.42

Elemental Analysis: C, 71.19; H, 6.87; N, 12.45; O, 9.48

Price and Availability

Size Price Availability Quantity
5mg USD 950.00 2 Weeks
10mg USD 1,650.00 2 Weeks
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Related CAS #
116839-68-0 (free base) 865795-23-9 (tartrate)
Synonym
Posiphen; R-phenserine; (+)-O-(Phenylcarbamoyl)eseroline; (+)-Phenserine; (+)-Phenylcarbamoyleseroline; (+)-Posiphen; buntanetap;
IUPAC/Chemical Name
(3aR,8aS)-1,3a,8-trimethyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indol-5-yl phenylcarbamate
InChi Key
PBHFNBQPZCRWQP-AZUAARDMSA-N
InChi Code
InChI=1S/C20H23N3O2/c1-20-11-12-22(2)18(20)23(3)17-10-9-15(13-16(17)20)25-19(24)21-14-7-5-4-6-8-14/h4-10,13,18H,11-12H2,1-3H3,(H,21,24)/t18-,20+/m0/s1
SMILES Code
O=C(NC1=CC=CC=C1)OC2=CC([C@]3(CCN([C@]34[H])C)C)=C(C=C2)N4C
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
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:
Buntanetap ((+)-Phenserine) is a novel selective cholinesterase noncompetitive inhibitor with an IC50 of 45.3 μM.
In vitro activity:
The effect of phenserine, a novel cholinesterase inhibitor, was assessed for the first time on kinetic parameters of human erythrocyte acetylcholinesterase (AChE). Phenserine (0.025-0.40 microM) inhibited the activity of human erythrocyte AChE in a concentration-dependent fashion, the IC50 was 0.0453 microM. Reference: Biochem Biophys Res Commun. 1998 Jul 9;248(1):180-5. https://pubmed.ncbi.nlm.nih.gov/9675107/
In vivo activity:
This study shows that Posiphen normalizes the colonic motility of both transgenic mouse models, although it did not affect the Whole Gut Transit Time (WGTT). 10 mg/kg Posiphen reduced α-synuclein levels in the gut of hSNCAA53T mice treated for twenty-one weeks, while 50 and 65 mg/kg Posiphen reduced α-synuclein levels in the brain of hSNCAA53T mice treated for twenty-one days. In conclusion, this is the first study showing the preclinical efficacy of Posiphen in normalizing the colonic motility in mouse models of gastrointestinal dysfunction in early PD. Reference: Am J Neurodegener Dis. 2019 Feb 15;8(1):1-15. https://pubmed.ncbi.nlm.nih.gov/30906671/
Solvent mg/mL mM comments
Solubility
DMSO 230.0 681.64
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 337.42 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.

Recalculate based on batch purity %
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. Chen XQ, Barrero CA, Vasquez-Del Carpio R, Reddy EP, Fecchio C, Merali S, Deglincerti A, Fang C, Rogers J, Maccecchini ML. Posiphen Reduces the Levels of Huntingtin Protein through Translation Suppression. Pharmaceutics. 2021 Dec 7;13(12):2109. doi: 10.3390/pharmaceutics13122109. PMID: 34959389; PMCID: PMC8708689. 2. al-Jafari AA, Kamal MA, Greig NH, Alhomida AS, Perry ER. Kinetics of human erythrocyte acetylcholinesterase inhibition by a novel derivative of physostigmine: phenserine. Biochem Biophys Res Commun. 1998 Jul 9;248(1):180-5. doi: 10.1006/bbrc.1998.8931. PMID: 9675107. 3. Kuo YM, Nwankwo EI, Nussbaum RL, Rogers J, Maccecchini ML. Translational inhibition of α-synuclein by Posiphen normalizes distal colon motility in transgenic Parkinson mice. Am J Neurodegener Dis. 2019 Feb 15;8(1):1-15. PMID: 30906671; PMCID: PMC6420700. 4. Teich AF, Sharma E, Barnwell E, Zhang H, Staniszewski A, Utsuki T, Padmaraju V, Mazell C, Tzekou A, Sambamurti K, Arancio O, Maccecchini ML. Translational inhibition of APP by Posiphen: Efficacy, pharmacodynamics, and pharmacokinetics in the APP/PS1 mouse. Alzheimers Dement (N Y). 2018 Jan 18;4:37-45. doi: 10.1016/j.trci.2017.12.001. PMID: 29955650; PMCID: PMC6021259.
In vitro protocol:
1. Chen XQ, Barrero CA, Vasquez-Del Carpio R, Reddy EP, Fecchio C, Merali S, Deglincerti A, Fang C, Rogers J, Maccecchini ML. Posiphen Reduces the Levels of Huntingtin Protein through Translation Suppression. Pharmaceutics. 2021 Dec 7;13(12):2109. doi: 10.3390/pharmaceutics13122109. PMID: 34959389; PMCID: PMC8708689. 2. al-Jafari AA, Kamal MA, Greig NH, Alhomida AS, Perry ER. Kinetics of human erythrocyte acetylcholinesterase inhibition by a novel derivative of physostigmine: phenserine. Biochem Biophys Res Commun. 1998 Jul 9;248(1):180-5. doi: 10.1006/bbrc.1998.8931. PMID: 9675107.
In vivo protocol:
1. Kuo YM, Nwankwo EI, Nussbaum RL, Rogers J, Maccecchini ML. Translational inhibition of α-synuclein by Posiphen normalizes distal colon motility in transgenic Parkinson mice. Am J Neurodegener Dis. 2019 Feb 15;8(1):1-15. PMID: 30906671; PMCID: PMC6420700. 2. Teich AF, Sharma E, Barnwell E, Zhang H, Staniszewski A, Utsuki T, Padmaraju V, Mazell C, Tzekou A, Sambamurti K, Arancio O, Maccecchini ML. Translational inhibition of APP by Posiphen: Efficacy, pharmacodynamics, and pharmacokinetics in the APP/PS1 mouse. Alzheimers Dement (N Y). 2018 Jan 18;4:37-45. doi: 10.1016/j.trci.2017.12.001. PMID: 29955650; PMCID: PMC6021259.
1: Galasko D, Farlow MR, Lucey BP, Honig LS, Elbert D, Bateman R, Momper J, Thomas RG, Rissman RA, Pa J, Aslanyan V, Balasubramanian A, West T, Maccecchini M, Feldman HH. A multicenter, randomized, double-blind, placebo-controlled ascending dose study to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamic (PD) effects of Posiphen in subjects with early Alzheimer's Disease. Alzheimers Res Ther. 2024 Jul 5;16(1):151. doi: 10.1186/s13195-024-01490-z. PMID: 38970127; PMCID: PMC11225352. 2: Maccecchini ML, Mould DR. Comparative Analysis of Posiphen Pharmacokinetics across Different Species-Similar Absorption and Metabolism in Mouse, Rat, Dog and Human. Biomolecules. 2024 May 15;14(5):582. doi: 10.3390/biom14050582. PMID: 38785991; PMCID: PMC11117716. 3: Galasko D, Farlow MR, Lucey BP, Honig LS, Elbert D, Bateman R, Momper J, Thomas R, Rissman RA, Pa J, Aslanyan V, Balasubramanian A, West T, Maccecchini M, Feldman HH. A multicenter, randomized, double-blind, placebo-controlled ascending dose study to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamic (PD) effects of Posiphen in subjects with Early Alzheimer's Disease. medRxiv [Preprint]. 2024 Mar 22:2024.03.20.24304638. doi: 10.1101/2024.03.20.24304638. Update in: Alzheimers Res Ther. 2024 Jul 5;16(1):151. doi: 10.1186/s13195-024-01490-z. PMID: 38562783; PMCID: PMC10984053. 4: Alvarez R, Kurfis J, Hendrickson M, Sem DS. Real-time thiol detection in iPSC-derived neuron cultures using SemKur-IM, a novel fluorescent dithio probe. SLAS Discov. 2024 Apr;29(3):100127. doi: 10.1016/j.slasd.2023.11.003. Epub 2023 Nov 20. PMID: 38000947. 5: Fang C, Hernandez P, Liow K, Damiano E, Zetterberg H, Blennow K, Feng D, Chen M, Maccecchini M. Buntanetap, a Novel Translational Inhibitor of Multiple Neurotoxic Proteins, Proves to Be Safe and Promising in Both Alzheimer's and Parkinson's Patients. J Prev Alzheimers Dis. 2023;10(1):25-33. doi: 10.14283/jpad.2022.84. PMID: 36641607. 6: Millar PR, Gordon BA, Luckett PH, Benzinger TLS, Cruchaga C, Fagan AM, Hassenstab JJ, Perrin RJ, Schindler SE, Allegri RF, Day GS, Farlow MR, Mori H, Nübling G; Dominantly Inherited Alzheimer Network; Bateman RJ, Morris JC, Ances BM. Multimodal brain age estimates relate to Alzheimer disease biomarkers and cognition in early stages: a cross-sectional observational study. Elife. 2023 Jan 6;12:e81869. doi: 10.7554/eLife.81869. PMID: 36607335; PMCID: PMC9988262. 7: Delport A, Hewer R. The amyloid precursor protein: a converging point in Alzheimer's disease. Mol Neurobiol. 2022 Jul;59(7):4501-4516. doi: 10.1007/s12035-022-02863-x. Epub 2022 May 17. PMID: 35579846. 8: Batool S, Furqan T, Hasan Mahmood MS, Tweedie D, Kamal MA, Greig NH. In Silico and Ex Vivo Analyses of the Inhibitory Action of the Alzheimer Drug Posiphen and Primary Metabolites with Human Acetyl- and Butyrylcholinesterase Enzymes. ACS Pharmacol Transl Sci. 2022 Jan 12;5(2):70-79. doi: 10.1021/acsptsci.1c00200. PMID: 35178511; PMCID: PMC8845043. 9: Chen XQ, Barrero CA, Vasquez-Del Carpio R, Reddy EP, Fecchio C, Merali S, Deglincerti A, Fang C, Rogers J, Maccecchini ML. Posiphen Reduces the Levels of Huntingtin Protein through Translation Suppression. Pharmaceutics. 2021 Dec 7;13(12):2109. doi: 10.3390/pharmaceutics13122109. PMID: 34959389; PMCID: PMC8708689. 10: Jicha GA, Abner EL, Arnold SE, Carrillo MC, Dodge HH, Edland SD, Fargo KN, Feldman HH, Goldstein LB, Hendrix J, Peters R, Robillard JM, Schneider LS, Titiner JR, Weber CJ; Clinical Trial Advancement & Methodology Professional Interest Area of the International Society to Advance Alzheimer's Research and Treatment (ISTAART). Committee on High-quality Alzheimer's Disease Studies (CHADS) consensus report. Alzheimers Dement. 2022 Jun;18(6):1109-1118. doi: 10.1002/alz.12461. Epub 2021 Sep 29. PMID: 34590417; PMCID: PMC8960469. 11: Winand L, Schneider P, Kruth S, Greven NJ, Hiller W, Kaiser M, Pietruszka J, Nett M. Mutasynthesis of Physostigmines in Myxococcus xanthus. Org Lett. 2021 Aug 20;23(16):6563-6567. doi: 10.1021/acs.orglett.1c02374. Epub 2021 Aug 6. PMID: 34355569. 12: Shadyab AH, LaCroix AZ, Feldman HH, van Dyck CH, Okonkwo OC, Tam SP, Fairchild JK, Welsh-Bohmer KA, Matthews G, Bennett D, Shadyab AA, Schafer KA, Morrison RH, Kipperman SA, Mason J, Tan D, Thomas RG, Cotman CW, Baker LD; ADCS EXERT Study Group. Recruitment of a multi-site randomized controlled trial of aerobic exercise for older adults with amnestic mild cognitive impairment: The EXERT trial. Alzheimers Dement. 2021 Nov;17(11):1808-1817. doi: 10.1002/alz.12401. Epub 2021 Jul 23. PMID: 34297895; PMCID: PMC9292825. 13: Chen XQ. A pilot exploration with Posiphen to normalize amyloid precursor protein in Down syndrome. Neural Regen Res. 2021 Dec;16(12):2420-2421. doi: 10.4103/1673-5374.313044. PMID: 33907026; PMCID: PMC8374580. 14: Ghiam MK, Patel SD, Hoffer A, Selman WR, Hoffer BJ, Hoffer ME. Drug Repurposing in the Treatment of Traumatic Brain Injury. Front Neurosci. 2021 Mar 23;15:635483. doi: 10.3389/fnins.2021.635483. PMID: 33833663; PMCID: PMC8021906. 15: Košak U, Gobec S. A Simple and Effective Synthesis of 3- and 4-((Phenylcarbamoyl)oxy)benzoic Acids. Acta Chim Slov. 2020 Sep;67(3):940-948. PMID: 33533422. 16: Smith RX, Strain JF, Tanenbaum A, Fagan AM, Hassenstab J, McDade E, Schindler SE, Gordon BA, Xiong C, Chhatwal J, Jack C Jr, Karch C, Berman S, Brosch JR, Lah JJ, Brickman AM, Cash DM, Fox NC, Graff-Radford NR, Levin J, Noble J, Holtzman DM, Masters CL, Farlow MR, Laske C, Schofield PR, Marcus DS, Morris JC, Benzinger TLS, Bateman RJ, Ances BM. Resting-State Functional Connectivity Disruption as a Pathological Biomarker in Autosomal Dominant Alzheimer Disease. Brain Connect. 2021 Apr;11(3):239-249. doi: 10.1089/brain.2020.0808. Epub 2021 Mar 31. PMID: 33430685; PMCID: PMC8182476. 17: Banks SJ, Qiu Y, Fan CC, Dale AM, Zou J, Askew B, Feldman HH; Alzheimer's Disease Neuroimaging Initiative. Enriching the design of Alzheimer's disease clinical trials: Application of the polygenic hazard score and composite outcome measures. Alzheimers Dement (N Y). 2020 Sep 13;6(1):e12071. doi: 10.1002/trc2.12071. PMID: 32999917; PMCID: PMC7507583. 18: Chen XQ, Salehi A, Pearn ML, Overk C, Nguyen PD, Kleschevnikov AM, Maccecchini M, Mobley WC. Targeting increased levels of APP in Down syndrome: Posiphen-mediated reductions in APP and its products reverse endosomal phenotypes in the Ts65Dn mouse model. Alzheimers Dement. 2021 Feb;17(2):271-292. doi: 10.1002/alz.12185. Epub 2020 Sep 25. PMID: 32975365; PMCID: PMC7984396. 19: Yu SJ, Wu KJ, Bae E, Wang YS, Chiang CW, Kuo LW, Harvey BK, Greig NH, Wang Y. Post-treatment with Posiphen Reduces Endoplasmic Reticulum Stress and Neurodegeneration in Stroke Brain. iScience. 2020 Feb 21;23(2):100866. doi: 10.1016/j.isci.2020.100866. Epub 2020 Jan 28. PMID: 32058974; PMCID: PMC7013187. 20: Greig NH, Lecca D, Hsueh SC, Nogueras-Ortiz C, Kapogiannis D, Tweedie D, Glotfelty EJ, Becker RE, Chiang YH, Hoffer BJ. (-)-Phenserine tartrate (PhenT) as a treatment for traumatic brain injury. CNS Neurosci Ther. 2020 Jun;26(6):636-649. doi: 10.1111/cns.13274. Epub 2019 Dec 11. PMID: 31828969; PMCID: PMC7248544.