UCM-1306 is an orally bioavailable allosteric modulator (PAM) of the human dopamine D1 receptor. UCM-1306 maximally increases endogenous dopamine (DA) in human and mouse D1 receptors. UCM-1306 not only improves motor symptoms but also addresses key comorbid cognitive impairments associated with long-term PD/Parkinson's disease.

Physicochemical Properties

Molecular Formula	C14H14FNO2S
Molecular Weight	279.329865932465
Exact Mass	279.072
CAS #	2258608-78-3
PubChem CID	137364063
Appearance	White to off-white solid powder
LogP	4.5
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	4
Heavy Atom Count	19
Complexity	387
Defined Atom Stereocenter Count	0
InChi Key	VCSBOASGFYJGGT-UHFFFAOYSA-N
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
Chemical Name	[4-[2-(fluoromethoxy)phenyl]phenyl]-imino-methyl-oxo-λ6-sulfane
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 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.
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].
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.
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.

Solubility Data

Solubility (In Vitro)

DMSO: 50 mg/mL (179.00 mM)

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.