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| 5mg |
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| 10mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
TAK-071 targets the muscarinic M1 acetylcholine receptor (M1R), a G protein-coupled receptor that is predominantly expressed in the central nervous system, particularly in regions involved in cognition such as the cortex and hippocampus. M1R is activated by the neurotransmitter acetylcholine and plays a critical role in learning, memory, and attention. TAK-071 is a positive allosteric modulator (PAM) with low cooperativity, meaning it enhances the receptor's response to acetylcholine without directly activating the receptor. This mechanism of action offers the potential for improved cognitive function with fewer cholinergic side effects compared to orthosteric agonists. TAK-071 activates M1R with an EC50 of 520 nM.
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| ln Vitro |
TAK-071 demonstrates potent and selective modulation of M1R activity. The compound activates M1R with an EC50 of 520 nM. In cellular assays, TAK-071 enhances M1R-mediated signaling in response to acetylcholine, increasing the potency and efficacy of the endogenous agonist. The compound's low cooperativity ensures that its effects are dependent on the presence of acetylcholine, reducing the risk of receptor overstimulation. TAK-071 has been shown to be highly selective for M1R over other muscarinic receptor subtypes, minimizing off-target effects. The compound's activity profile makes it a valuable tool for studying M1R-dependent pathways in cognitive function.
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| ln Vivo |
At a dose of 0.3 mg/kg, TAK-071 ameliorates the cognitive impairments caused by DB00747 in rats via increasing hippocampus myo-inositol monophosphate synthesis via M1R activation [1]. At 10 mg/kg, TAK-071 also induces diarrhea in rats [1]. Rats with DB00747-induced cognitive impairments showed considerable improvement when acetylcholinesterase inhibitors and TAK-071 (3 mg/kg) were combined [1].
TAK-071 has demonstrated efficacy in improving cognitive function in rodent models. The compound enhances performance in various cognitive tasks, including those assessing learning and memory. Importantly, TAK-071 produces these cognitive benefits with few cholinergic side effects, such as those commonly associated with non-selective muscarinic agonists or acetylcholinesterase inhibitors. The compound's low cooperativity and selectivity for M1R contribute to its favorable side effect profile. Detailed in vivo efficacy data, including specific cognitive test results and dosing regimens, are available in the primary literature. TAK-071 is a valuable tool for evaluating therapeutic strategies for cognitive disorders such as Alzheimer's disease and schizophrenia. |
| Enzyme Assay |
The in vitro receptor binding assay for TAK-071 measures the binding affinity and allosteric modulation of M1R. Radioligand binding assays are performed using membrane preparations from cells expressing the human M1 receptor. Varying concentrations of TAK-071 (typically ranging from nanomolar to micromolar) are incubated with the membrane preparation and a radiolabeled orthosteric ligand. The ability of TAK-071 to modulate the binding of the orthosteric ligand is assessed. Alternatively, functional assays measuring calcium mobilization or other downstream signaling events are used to evaluate allosteric modulation. The compound is dissolved in DMSO and diluted in assay buffer to achieve the desired final concentrations. Appropriate positive controls (known M1 PAMs) and negative controls are included in each assay run.
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| Cell Assay |
The in vitro cellular assay for TAK-071 is performed using cells expressing the human M1 receptor, such as CHO or HEK293 cells stably transfected with M1R. Cells are cultured in appropriate medium and loaded with a calcium-sensitive fluorescent dye. Cells are treated with varying concentrations of TAK-071 or vehicle control (DMSO) prior to stimulation with a submaximal concentration of acetylcholine. The increase in intracellular calcium is measured using a fluorescence plate reader. The potentiation of the acetylcholine response by TAK-071 is quantified, and EC50 values are determined by fitting dose-response curves. The selectivity of TAK-071 for M1R over other muscarinic receptor subtypes (M2-M5) is assessed using similar assays in cells expressing each subtype.
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| Animal Protocol |
In vivo animal experiments with TAK-071 are typically conducted using rodent models of cognitive impairment, such as aged rats, scopolamine-treated mice, or transgenic Alzheimer's disease models. TAK-071 is administered via oral gavage or intraperitoneal injection at various doses. Cognitive function is assessed using behavioral tasks such as the Morris water maze, novel object recognition, or passive avoidance tests. The compound's effects on learning and memory are compared to vehicle-treated controls. Additionally, side effects such as salivation, tremor, and hypothermia are monitored to assess cholinergic side effect liability. At the end of the study, brain tissues may be harvested for analysis of receptor occupancy and downstream signaling markers.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic (PK) parameters for TAK-071 are not extensively documented in publicly available sources. As a small-molecule PAM with a molecular weight of 421.46, the compound is expected to have reasonable oral bioavailability and good central nervous system penetration. TAK-071 has a chemical formula of C24H24FN3O3. For in vivo administration, the compound is typically formulated using appropriate vehicles to ensure adequate solubility and stability. The compound should be stored under conditions recommended by the manufacturer to maintain stability and prevent degradation. Detailed PK parameters including half-life, clearance, volume of distribution, and maximum concentration (Cmax) are available in the primary literature and should be consulted for specific experimental planning.
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| Toxicity/Toxicokinetics |
Comprehensive toxicological data for TAK-071 are not extensively documented in publicly available sources. As a research-grade compound, TAK-071 is intended for laboratory research purposes only and is not approved for human therapeutic use. Standard laboratory safety practices should be followed when handling this compound, including the use of appropriate personal protective equipment and working in a well-ventilated area. In animal studies, TAK-071 has been reported to produce few cholinergic side effects, suggesting a favorable tolerability profile. However, comprehensive toxicological profiling (e.g., LD50, maximum tolerated dose, organ-specific toxicity) is not available from the current search results and would require consultation of the primary literature or safety data sheets.
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| References | |
| Additional Infomation |
TAK-071 is a research compound developed for studying the role of M1 muscarinic receptors in cognitive function. The compound is a potent and selective positive allosteric modulator of M1R with low cooperativity, meaning it enhances the receptor's response to acetylcholine without directly activating it. TAK-071 has demonstrated efficacy in improving cognitive function in rodent models with few cholinergic side effects. The compound is a valuable tool for probing M1R-dependent pathways and evaluating therapeutic strategies for cognitive disorders such as Alzheimer's disease and schizophrenia. TAK-071 is not currently in clinical trials nor approved for therapeutic use; it remains an investigational tool compound for preclinical neuroscience research. The compound is available from various chemical suppliers for research purposes.
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| Molecular Formula |
C24H24FN3O3
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| Molecular Weight |
421.464069366455
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| Exact Mass |
421.18
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| CAS # |
1820812-16-5
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| PubChem CID |
92042879
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| Appearance |
White to off-white solid powder
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| LogP |
2.7
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
31
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| Complexity |
644
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| Defined Atom Stereocenter Count |
2
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| SMILES |
FC1=C(C)C(CC2C=CC(=CC=2)N2C=CC=N2)=CC2C(N(CC=21)[C@H]1COCC[C@@H]1O)=O
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| InChi Key |
WFSARWQASFQZMG-VXKWHMMOSA-N
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| InChi Code |
InChI=1S/C24H24FN3O3/c1-15-17(11-16-3-5-18(6-4-16)28-9-2-8-26-28)12-19-20(23(15)25)13-27(24(19)30)21-14-31-10-7-22(21)29/h2-6,8-9,12,21-22,29H,7,10-11,13-14H2,1H3/t21-,22-/m0/s1
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| Chemical Name |
4-fluoro-2-[(3S,4S)-4-hydroxyoxan-3-yl]-5-methyl-6-[(4-pyrazol-1-ylphenyl)methyl]-3H-isoindol-1-one
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| Synonyms |
TAK-071; TAK 071; TAK071
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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 |
| 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 : ~135 mg/mL (~320.32 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.25 mg/mL (5.34 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 22.5 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: ≥ 2.25 mg/mL (5.34 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 22.5 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: ≥ 2.25 mg/mL (5.34 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 | 2.3727 mL | 11.8635 mL | 23.7270 mL | |
| 5 mM | 0.4745 mL | 2.3727 mL | 4.7454 mL | |
| 10 mM | 0.2373 mL | 1.1864 mL | 2.3727 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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