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Taltirelin acetate (TA-0910; trade name Ceredist) is a thyrotropin-releasing hormone (TRH) analog and a TRH mimic that stimulates an increase in cytosolic Ca2+ concentration (Ca2+ release) as a superagonist at thyrotropin-releasing hormone receptor (TRH-R) with an IC50 of 910 nM and an EC50 of 36 nM. By activating descending monoaminergic neurons in persistent inflammatory pain, taltirelin reduces mechanical allodynia. In contrast to TRH, it has a substantially longer half-life, a longer duration of action, and minimal tolerance development after repeated dosage. It has analgesic, neuroprotective, and nootropic properties.
| Targets |
Thyrotropin-releasing hormone receptor (IC50 = 910 nM)
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|---|---|
| ln Vitro |
Taltirelin binds to the human TRH receptor with lower affinity (IC₅₀ = 910 nM) compared to TRH (IC₅₀ = 36 nM) in HEK-EM 293 cells stably expressing TRH-R.
Taltirelin exhibits moderate potency in stimulating intracellular calcium mobilization (EC₅₀ = 36 nM), lower than TRH (EC₅₀ = 5.0 nM). However, Taltirelin demonstrates higher intrinsic efficacy than TRH. It stimulates inositol-1,4,5-trisphosphate (IP3) pathway activation more effectively, as measured by IP1 accumulation. The EC₅₀ for IP1 production is 150 nM for Taltirelin versus 3.9 nM for TRH. At maximal receptor occupancy, Taltirelin stimulates IP1 production that is 180% of the level stimulated by TRH, classifying it as a superagonist at the human TRH receptor. The partial agonist MeTRH can inhibit the IP1 response stimulated by both TRH and Taltirelin, confirming the efficacy hierarchy (MeTRH < TRH < Taltirelin). |
| Cell Assay |
HEK-EM 293 cells were stably transfected with human TRH-R cDNA and cultured in DMEM supplemented with 10% fetal bovine serum and hygromycin for selection.
For competition binding assays, cells were seeded in 24-well plates. Cells were preincubated with various concentrations of unlabeled Taltirelin, TRH, or MeTRH for 15 minutes, followed by incubation with 4 nM [³H]MeTRH for 1 hour at 37°C. Non-specific binding was determined in the presence of excess unlabeled MeTRH. For intracellular calcium mobilization, cells were seeded in black-walled, clear-bottom 96-well plates. After 24 hours, cells were loaded with a fluorescent calcium-sensitive dye for 1 hour. Ligand-induced changes in intracellular calcium concentration were measured using a fluorescence imaging plate reader system upon addition of compounds. For IP1 production measurement, cells were seeded in 24-well plates. Serial dilutions of ligands were added in Hank’s balanced salt solution containing LiCl (to inhibit IP1 degradation). After 60 minutes of incubation at 37°C, IP1 content was quantified using a commercial ELISA kit according to the manufacturer's instructions. Data analysis for dose-response and competition binding was performed using non-linear regression curve fitting. [1] |
| References | |
| Additional Infomation |
Tatriptyline is an analogue of thyrotropin-releasing hormone (TRH). It is approved in Japan under the brand name Ceredist® for the treatment of spinal muscular atrophy in adults. Compared to TRH, tatriptyline has been reported in other studies (cited but not elaborated in this article) to have greater blood stability, stronger blood-brain barrier penetration, and stronger rodent central nervous system (CNS) activity. The TRH receptor hyperagonism observed in this study may also contribute to its enhanced CNS effects in humans. [1]
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| Molecular Formula |
C17H23N7O5
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|---|---|
| Molecular Weight |
405.408422708511
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| Exact Mass |
465.197
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| CAS # |
1549593-23-8
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| Related CAS # |
Taltirelin;103300-74-9;Taltirelin-13C,d3
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| PubChem CID |
86346477
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| Appearance |
White to off-white solid
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
6
|
| Heavy Atom Count |
33
|
| Complexity |
745
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| Defined Atom Stereocenter Count |
3
|
| SMILES |
CC(=O)O.CN1C(=O)C[C@H](NC1=O)C(=O)N[C@@H](CC2=CN=CN2)C(=O)N3CCC[C@H]3C(=O)N
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| InChi Key |
AQWPSTSKDKFSRT-LFELFHSZSA-N
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| InChi Code |
InChI=1S/C17H23N7O5.C2H4O2/c1-23-13(25)6-10(22-17(23)29)15(27)21-11(5-9-7-19-8-20-9)16(28)24-4-2-3-12(24)14(18)26;1-2(3)4/h7-8,10-12H,2-6H2,1H3,(H2,18,26)(H,19,20)(H,21,27)(H,22,29);1H3,(H,3,4)/t10-,11-,12-;/m0./s1
|
| Chemical Name |
acetic acid;(4S)-N-[(2S)-1-[(2S)-2-carbamoylpyrrolidin-1-yl]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]-1-methyl-2,6-dioxo-1,3-diazinane-4-carboxamide
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| Synonyms |
TA-0910 acetate; TA0910 acetate; TA 0910 acetate
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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: ~125 mg/mL (~268.6 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.47 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 20.8 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: ≥ 2.08 mg/mL (4.47 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 20.8 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: ≥ 2.08 mg/mL (4.47 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 | 2.4666 mL | 12.3332 mL | 24.6664 mL | |
| 5 mM | 0.4933 mL | 2.4666 mL | 4.9333 mL | |
| 10 mM | 0.2467 mL | 1.2333 mL | 2.4666 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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