| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
AChE
The primary target of P11149 is acetylcholinesterase (AChE). It acts as a competitive inhibitor, showing selectivity for AChE. It exhibits an IC50 of 1.3 microM for rat BChE/AChE, demonstrating moderate potency. It is a galanthamine (GAL) analog and is rapidly hydrolyzed in vivo to 6-DMG, which is a more potent AChE inhibitor. |
|---|---|
| ln Vitro |
In vitro, P11149 inhibits rat BChE/AChE with an IC50 of 1.3 uM. It acts as a competitive, selective inhibitor of AChE. It is a galanthamine analog that is rapidly hydrolyzed in vivo to yield the potent AChE inhibitor 6-DMG. The parent compound itself shows central cholinergic activity.
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| ln Vivo |
P11149, a GAL analog, hydrolyzes quickly in vivo to produce 6-DMG, a strong AChE inhibitor[1]. Compared to po, P11149 has higher sc bioavailability [1]. While 6-DMG, P1 1012, and GAL produce Sal and Lac at lower dosages than those in rats, oral P11149 in mice causes tremors, Sal, and Lac at concentrations comparable to those in rats[1]. In rat plasma, P11149 shows a T1/2(el) of 2.4 hours and a Cmax of 585 ng/mL[ 1].
In vivo, P11149 is orally active and demonstrates central cholinergic activity, behavioral efficacy, and safety. It exhibits greater subcutaneous (s.c.) bioavailability than oral (p.o.) bioavailability. In mice, oral P11149 produces salivation, lacrimation, and tremors at doses similar to those in rats, which is consistent with its mechanism of AChE inhibition. It is used in the study for Alzheimer‘s disease. |
| Enzyme Assay |
The inhibition of AChE is determined using a standard colorimetric Ellman assay. Rat brain homogenate or purified AChE is incubated with varying concentrations of P11149 in a 96-well plate. The substrate acetylthiocholine and DTNB are added, and the yellow color development is monitored at 412 nm. The IC50 is calculated by plotting percent inhibition against the log of the compound concentration.
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| Cell Assay |
In vivo behavioral efficacy is the primary functional readout, but ex vivo AChE activity can be measured in brain tissue. After oral administration of P11149 to rats, the animals are sacrificed, and the cortex or hippocampus is dissected and homogenized. The homogenate is centrifuged, and the supernatant is assayed for residual AChE activity using the Ellman method to confirm target engagement.
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| Animal Protocol |
A standard in vivo protocol for P11149 involves administering the compound orally (p.o.) or subcutaneously (s.c.) to rats or mice. For behavioral studies, doses of P11149 (e.g., 1-10 mg/kg) are given to rats or mice, and cholinergic side effects (salivation, lacrimation, tremors) are observed and scored. For pharmacokinetic studies, serial blood samples are collected via tail vein or cardiac puncture for LC-MS/MS analysis.
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| ADME/Pharmacokinetics |
P11149 exhibits a half-life (T1/2(el)) of 2.4 hours and reaches a maximum concentration (Cmax) of 585 ng/mL in rat plasma after oral administration. It has greater subcutaneous (s.c.) bioavailability than oral (p.o.) bioavailability. It is a galanthamine analog that is rapidly hydrolyzed in vivo to yield the potent AChE inhibitor 6-DMG.
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| Toxicity/Toxicokinetics |
No detailed toxicological data is provided. As an AChE inhibitor, P11149 would be expected to produce classic cholinergic side effects (salivation, lacrimation, tremors) at high doses, which are considered on-target toxicities. In the references, these effects are noted as pharmacological endpoints rather than adverse events, indicating that the compound has a predictable safety margin based on its mechanism of action.
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| References | |
| Additional Infomation |
P11149 was developed as a novel Alzheimer‘s disease therapeutic based on the galanthamine scaffold. It was designed to have an improved pharmacological profile, with the unique property of being a prodrug that is rapidly hydrolyzed in vivo to an even more potent AChE inhibitor (6-DMG). This “metabolic activation” strategy distinguishes it from other AChE inhibitors and has been the subject of pharmacological evaluation for its behavioral efficacy, safety, and central cholinergic activity.
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| Molecular Formula |
C27H33NO4
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|---|---|
| Molecular Weight |
472.016167163849
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| Exact Mass |
471.217
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| CAS # |
164724-79-2
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| PubChem CID |
9912659
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
33
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| Complexity |
783
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| Defined Atom Stereocenter Count |
3
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| SMILES |
O(C1=CC=C2CN(C)CC[C@@]34C=C[C@H](O)C[C@]3([H])OC1=C42)C(C12CC3CC(CC(C3)C1)C2)=O.Cl
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| InChi Key |
NXIVVAIJLAXRRL-COWQPDHPSA-N
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| InChi Code |
InChI=1S/C27H33NO4.ClH/c1-28-7-6-27-5-4-20(29)11-22(27)32-24-21(3-2-19(15-28)23(24)27)31-25(30)26-12-16-8-17(13-26)10-18(9-16)14-26;/h2-5,16-18,20,22,29H,6-15H2,1H3;1H/t16?,17?,18?,20-,22-,26?,27-;/m0./s1
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| Chemical Name |
[(1S,12S,14R)-14-hydroxy-4-methyl-11-oxa-4-azatetracyclo[8.6.1.01,12.06,17]heptadeca-6(17),7,9,15-tetraen-9-yl] adamantane-1-carboxylate;hydrochloride
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO: 100 mg/mL (211.86 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (10.59 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% 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 50.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 5 mg/mL (10.59 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 50.0 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. View More
Solubility in Formulation 3: ≥ 5 mg/mL (10.59 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1186 mL | 10.5928 mL | 21.1855 mL | |
| 5 mM | 0.4237 mL | 2.1186 mL | 4.2371 mL | |
| 10 mM | 0.2119 mL | 1.0593 mL | 2.1186 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.
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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