| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Targets |
The primary target of UCM-1306 is the dopamine D1 receptor (D1R). It functions as a positive allosteric modulator (PAM), meaning it binds to a site distinct from the orthosteric dopamine binding site. This binding increases the maximal effect of endogenous dopamine (DA), increasing its potency and efficacy at both human and mouse D1 receptors.
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| ln Vitro |
The concentration-responsive enhancement of cAMP by UCM-1306 (2-(Fluoromethoxy)-4'-(S-methylsulfonimidoyl)-1,1'-biphenyl; 1-10 μM) has an EC50=60 nM.
In vitro, UCM-1306 acts as a PAM, increasing the maximal effect of endogenous dopamine (DA) at D1 receptors. It enhances dopamine's efficacy in both human and mouse D1 receptors. By modulating rather than directly activating the receptor, it has a distinct pharmacological profile from full orthosteric agonists. |
| ln Vivo |
Good oral availability and brain penetration are features of UCM-1306 (2-(Fluoromethoxy)-4'-(S-methylsulfonimidoyl)-1,1'-biphenyl; 5 mg/kg; po; C57BL/6J mice). With a Tmax of 0.5 hours, plasma concentrations can be measured in 8 hours[1]. In adult mice, UCM-1306 (1 mg/kg; ip) amplifies the hyperlocomotion caused by cocaine[1]. Consolidating the establishment of long-term memory is aided by UCM-1306 (1 mg/kg; ip)[1].
In vivo, UCM-1306 (1 mg/kg, ip) amplifies the hyperlocomotion caused by cocaine in adult mice. It also aids in the consolidation of long-term memory. This compound is not only for improving motor symptoms but also for addressing the key comorbid cognitive impairment associated with long-term Parkinson‘s disease (PD). |
| Enzyme Assay |
The binding of UCM-1306 is studied indirectly through functional allosteric modulation assays, not direct binding. A non-cellular protocol uses membrane preparations from cells expressing human D1 receptors. Membranes are pre-incubated with UCM-1306 and then stimulated with a sub-maximal concentration of dopamine. The enhancement of [35S]GTPgammaS binding (G-protein activation) is measured as a readout of PAM activity.
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| Cell Assay |
A standard cellular protocol for D1 PAMs uses HEK-293 cells expressing the D1 receptor and a CRE-luciferase reporter. Cells are treated with a fixed sub-maximal concentration of dopamine (e.g., EC20) plus varying concentrations of UCM-1306. After incubation (e.g., 4-6 h), luciferase activity is measured. An increase in luminescence indicates PAM activity, and fold-shift in dopamine EC50 is calculated.
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| Animal Protocol |
Animal/Disease Models: Adult C57BL/6J mice with cocaine-induced hyperactivity model[1]
Doses: 1 mg/kg; cocaine (20 mg/kg, sc) Route of Administration: intraperitoneal (ip) injection Experimental Results: Increased cocaine-induced hyperlocomotion, suggesting an in vivo potentiation of DA action at the D1R. Animal/Disease Models: Adult C57BL/6J mice Doses: 1 mg/kg Route of Administration: intraperitoneal (ip) injection Experimental Results: Increased memory trace in C57BL/6J mice. An in vivo protocol for UCM-1306 in memory studies involves administering UCM-1306 (1 mg/kg, ip) to adult mice 30 minutes before training in an object recognition or passive avoidance task. Retention is tested 24 hours later. Enhanced memory retention in treated mice compared to vehicle controls indicates that D1 PAM activity facilitates long-term memory consolidation. |
| ADME/Pharmacokinetics |
No specific pharmacokinetic data for UCM-1306 is provided. As an orally active modulator, it is expected to be well-absorbed and to penetrate the CNS. The effective dose of 1 mg/kg in mice via intraperitoneal injection suggests it has good systemic bioavailability via this route.
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| Toxicity/Toxicokinetics |
Dopamine D1 receptors are involved in motor control and cognition. As a PAM, UCM-1306 is expected to have a different toxicity profile than orthosteric agonists, potentially reducing risks like dyskinesia or psychosis associated with overstimulation of the receptor. No specific toxicity data is provided in these sources.
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| References |
[1]. García-Cárceles J, et, al. 2-(Fluoromethoxy)-4'-(S-methanesulfonimidoyl)-1,1'-biphenyl (UCM-1306), an Orally Bioavailable Positive Allosteric Modulator of the Human Dopamine D1 Receptor for Parkinson's Disease. J Med Chem. 2022 Sep 22;65(18):12256-12272.
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| Additional Infomation |
UCM-1306 is a unique pharmacological tool because it targets the D1 receptor allosterically. This mechanism offers potential therapeutic advantages over traditional D1 agonists by fine-tuning, rather than blasting, the endogenous dopamine signal. This could improve symptoms of Parkinson's disease (motor and cognitive) without the desensitization and dyskinesia that limit the use of orthosteric agonists.
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| Molecular Formula |
C14H14FNO2S
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| Molecular Weight |
279.329865932465
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| Exact Mass |
279.072
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| CAS # |
2258608-78-3
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| PubChem CID |
137364063
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| Appearance |
White to off-white solid powder
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| LogP |
4.5
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
19
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| Complexity |
387
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CS(=N)(=O)C1=CC=C(C=C1)C2=CC=CC=C2OCF
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| InChi Key |
VCSBOASGFYJGGT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C14H14FNO2S/c1-19(16,17)12-8-6-11(7-9-12)13-4-2-3-5-14(13)18-10-15/h2-9,16H,10H2,1H3
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| Chemical Name |
[4-[2-(fluoromethoxy)phenyl]phenyl]-imino-methyl-oxo-λ6-sulfane
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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: 50 mg/mL (179.00 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.95 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 25.0 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.5800 mL | 17.9000 mL | 35.7999 mL | |
| 5 mM | 0.7160 mL | 3.5800 mL | 7.1600 mL | |
| 10 mM | 0.3580 mL | 1.7900 mL | 3.5800 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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