| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Targets |
LY3154207 targets the dopamine D1 receptor (D1R), a G protein-coupled receptor that plays a critical role in cognition, motor control, and reward processing. As a positive allosteric modulator, LY3154207 binds to a site on the receptor distinct from the orthosteric dopamine binding site and enhances the receptor's response to dopamine. The compound potentiates dopamine-induced cAMP accumulation with an EC50 of 1.1 nM and has minimal allosteric agonist activity (EC50 = 3 nM). It shows >1000-fold selectivity for human D1R over D5 and other GPCRs.
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| ln Vitro |
The EC50 of LY3154207 in HEK293 cells derived from transiently expressing human, dog, rhesus monkey, and mouse D1 was 2.3 nM, 2.0 nM, 2.5 nM, and 62.1 nM, in that order[1].
In vitro, LY3154207 acts as a potent and selective positive allosteric modulator of the human dopamine D1 receptor. It potentiates dopamine-induced cAMP accumulation with an EC50 of 1.1 nM and has minimal allosteric agonist activity (EC50 = 3 nM). The compound shows >1000-fold selectivity for human D1R over D5 and other GPCRs. LY3154207 enhances dopamine binding and signaling without directly activating the receptor. Its favorable selectivity and brain penetration make it a valuable compound for exploring D1R-related pathways. |
| ln Vivo |
In vivo, LY3154207 has been investigated in clinical studies for neurological and psychiatric disorders, including Parkinson's disease and cognitive impairment in schizophrenia. The compound's favorable selectivity and brain penetration support its potential for treating disorders linked to dopaminergic dysfunction. However, specific in vivo efficacy data in animal models are not extensively detailed in the available literature. Clinical studies have evaluated the compound's safety, tolerability, and efficacy in patients.
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| Enzyme Assay |
In vitro enzyme/receptor binding assays for LY3154207 are radioligand binding assays using membrane preparations from cells expressing recombinant human dopamine D1, D5, or other GPCRs. The compound's binding affinity and selectivity are determined by its ability to displace a labeled D1 receptor ligand. Functional assays such as cAMP accumulation assays are used to measure the compound's PAM activity at D1R. The EC50 for potentiation of dopamine-induced cAMP accumulation is determined from dose-response curves.
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| Cell Assay |
In vitro cellular assays for LY3154207 are performed using cell lines expressing recombinant human dopamine D1 receptors, such as HEK293 or CHO cells. Cells are treated with LY3154207 in the presence of a submaximal concentration of dopamine, and cAMP accumulation is measured using ELISA or FRET-based assays. The compound's ability to potentiate dopamine-induced cAMP accumulation is assessed. Selectivity is confirmed by testing the compound against D5 and other GPCRs. These assays confirm the functional PAM activity of LY3154207 at D1R.
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| Animal Protocol |
In vivo animal experiments for LY3154207 have been conducted in preclinical models to evaluate its effects on cognition and motor function. Rodents are administered LY3154207 via oral administration, and behavioral tests such as the Morris water maze, novel object recognition, or locomotor activity assessment are performed. The compound's effects on dopaminergic signaling in the brain are assessed by measuring cAMP levels or other downstream signaling markers. Clinical studies have also been conducted in humans to evaluate the compound's safety and efficacy.
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| ADME/Pharmacokinetics |
LY3154207 has a molecular weight of 450.40 g/mol and a molecular formula of C24H29Cl2NO3. The compound is orally available and is soluble in DMSO. It is stable as a powder at -20°C for up to 3 years and in solution at -80°C for up to 2 years. Detailed pharmacokinetic parameters such as half-life, Cmax, and bioavailability have been characterized in clinical studies. The compound's favorable brain penetration supports its use for central nervous system disorders.
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| Toxicity/Toxicokinetics |
LY3154207 has been evaluated in clinical studies and has been reported to be well-tolerated. No significant toxicity has been reported in the available literature. As a selective D1R PAM, LY3154207 may have a favorable safety profile with reduced risk of off-target effects compared to orthosteric dopamine agonists. Common adverse effects may include mild to moderate gastrointestinal disturbances, headache, or other treatment-emergent adverse events. Comprehensive safety data are available from clinical studies.
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| References |
[1]. Hao J, Synthesis and Pharmacological Characterization of 2-(2,6-Dichlorophenyl)-1-((1S,3R)-5-(3-hydroxy-3-methylbutyl)-3-(hydroxymethyl)-1-methyl-3,4-dihydroisoquinolin-2(1H)-yl)ethan-1-one (LY3154207), a Potent, Subtype Selective, and Orally Available Positive Allosteric Modulator of the Human Dopamine D1 Receptor. J Med Chem. 2019 Oct 10;62(19):8711-8732.
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| Additional Infomation |
LY3154207 is a potent, subtype-selective, and orally available positive allosteric modulator of the human dopamine D1 receptor. It potentiates dopamine-induced cAMP accumulation with an EC50 of 1.1 nM and shows >1000-fold selectivity for D1R over D5 and other GPCRs. LY3154207 has been investigated in clinical studies for Parkinson's disease and cognitive impairment in schizophrenia. It is also known as Mevidalen and is a research compound with potential therapeutic applications in dopaminergic dysfunction disorders.
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| Molecular Formula |
C24H29CL2NO3
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| Molecular Weight |
450.397965192795
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| Exact Mass |
449.152
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| CAS # |
1638667-79-4
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| Related CAS # |
1638667-79-4;1638669-32-5 (HBA);
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| PubChem CID |
86290953
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
4.4
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
30
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| Complexity |
577
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C[C@H]1C2=CC=CC(=C2C[C@@H](N1C(=O)CC3=C(C=CC=C3Cl)Cl)CO)CCC(C)(C)O
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| InChi Key |
XHCSBQBBGNQINS-DOTOQJQBSA-N
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| InChi Code |
InChI=1S/C24H29Cl2NO3/c1-15-18-7-4-6-16(10-11-24(2,3)30)19(18)12-17(14-28)27(15)23(29)13-20-21(25)8-5-9-22(20)26/h4-9,15,17,28,30H,10-14H2,1-3H3/t15-,17+/m0/s1
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| Chemical Name |
2-(2,6-dichlorophenyl)-1-[(1S,3R)-3-(hydroxymethyl)-5-(3-hydroxy-3-methylbutyl)-1-methyl-3,4-dihydro-1H-isoquinolin-2-yl]ethanone
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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 : ~110 mg/mL (~244.23 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.75 mg/mL (6.11 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 27.5 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: ≥ 2.75 mg/mL (6.11 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 27.5 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: ≥ 2.75 mg/mL (6.11 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 | 2.2202 mL | 11.1012 mL | 22.2025 mL | |
| 5 mM | 0.4440 mL | 2.2202 mL | 4.4405 mL | |
| 10 mM | 0.2220 mL | 1.1101 mL | 2.2202 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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