TAK-071 is a novel, potent and highly selective muscarinic acetylcholine receptor 1 (M1R) positive allosteric modulator (PAM). EC50 of TAK-071 M1R agonist activities is 520 nM. The muscarinic M1 receptor (M1R) is a promising target for treating cognitive impairment associated with cholinergic deficits in disorders such as Alzheimer's disease and schizophrenia.
Physicochemical Properties
| Molecular Formula | C24H24FN3O3 |
| Molecular Weight | 421.464069366455 |
| Exact Mass | 421.18 |
| CAS # | 1820812-16-5 |
| PubChem CID | 92042879 |
| Appearance | White to off-white solid powder |
| LogP | 2.7 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 31 |
| Complexity | 644 |
| Defined Atom Stereocenter Count | 2 |
| SMILES | FC1=C(C)C(CC2C=CC(=CC=2)N2C=CC=N2)=CC2C(N(CC=21)[C@H]1COCC[C@@H]1O)=O |
| InChi Key | WFSARWQASFQZMG-VXKWHMMOSA-N |
| 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 |
| Chemical Name | 4-fluoro-2-[(3S,4S)-4-hydroxyoxan-3-yl]-5-methyl-6-[(4-pyrazol-1-ylphenyl)methyl]-3H-isoindol-1-one |
| Synonyms | TAK-071; TAK 071; TAK071 |
| 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 |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| 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]. |
| References |
[1]. TAK-071, a novel M1 positive allosteric modulator with low cooperativity, improves cognitive function in rodents with few cholinergic side effects. Neuropsychopharmacology. 2018 Aug 1. doi: 10.1038/s41386-018-0168-8. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~135 mg/mL (~320.32 mM) |
| 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. 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. 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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| 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 |