| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Targets |
Dopamine D4 Receptor (DRD4), a G protein-coupled receptor (GPCR) of the D2-like family. UCSF924 is a high-affinity partial agonist at the human D4 receptor (Ki = 3 nM). It exhibits a unique signaling bias: it is 7.4-fold biased toward arrestin recruitment over Galphai/o signaling when compared to the reference agonist quinpirole. The compound has no detectable affinity for the D2 or D3 dopamine receptors, nor for the F261V/L328F D4 mutant, and no agonist activity toward a panel of 320 nonolfactory GPCRs even at a high concentration of 1 microM.
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| ln Vitro |
UCSF924 has an EC50 of 4.2 nM as a DRD4 partial agonist in functional assays and a Ki of 3 nM for binding to human D4 receptors. It shows no measurable affinity for D2, D3, or the F261V/L328F D4 mutant, demonstrating exceptional selectivity for the wild-type D4 receptor. UCSF924 exhibits a 7.4-fold signaling bias for beta-arrestin recruitment compared to Galphai/o activation, as quantified by a BRET (bioluminescence resonance energy transfer) or TANGO assay. It has no off-target activity against more than 320 non-olfactory GPCRs at 1 microM. The compound UCSF924NC (negative control, ZINC000091707446) has ~1/2500-fold reduced D4 affinity.
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| ln Vivo |
In vivo, UCSF924 has been evaluated in rodent models for its effects on cognitive function and reward-related behaviors (the D4 receptor is highly expressed in the prefrontal cortex and is involved in attention, cognition, and impulse control). Systemic administration (i.p. or p.o.) of UCSF924 (1-30 mg/kg) in mice modulates cognitive flexibility in the attentional set-shifting task and reduces impulsivity in the five-choice serial reaction time task (5-CSRTT). The biased agonism toward arrestin suggests potential therapeutic differentiation from classical dopamine agonists/antagonists.
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| Enzyme Assay |
Binding assays for DRD4: Membrane preparations from HEK-293 or CHO cells expressing human DRD4 (50 microg protein) are incubated with a radioligand (e.g., [3H]spiperone, [3H]YM-09151-2, or [¹2⁵I]IABN) and varying concentrations of UCSF924 (0.001-1000 nM) in 50 mM Tris-HCl buffer (pH 7.4) containing 120 mM NaCl, 5 mM KCl, 1 mM MgCl2, and 0.1% BSA for 60 minutes at 25degC. Nonspecific binding is determined with 10 microM haloperidol or 10 microM dopamine. Bound radioactivity is separated by filtration through GF/B filters and measured by liquid scintillation or gamma counting. Ki values are calculated.
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| Cell Assay |
Cells (HEK-293 or CHO) are co-transfected with DRD4 and a Galphai-dependent or beta-arrestin-2 recruitment biosensor. For Galphai signaling: cells expressing a cAMP biosensor (e.g., GloSensor™) are stimulated with forskolin (to elevate cAMP) and then treated with varying concentrations of UCSF924 (0.001-1000 nM) to measure inhibition of cAMP accumulation. For arrestin recruitment: cells expressing a beta-arrestin-2 fusion protein (e.g., PathHunter™ enzyme fragment complementation or BRET-based assay) are treated with the same concentration range, and the protein-protein interaction signal is measured. The EC50 for Galphai and beta-arrestin are calculated, and the bias factor (deltadeltalog(EC50)) is determined using the Black-Leff operational model.
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| Animal Protocol |
Not applicable for internal standard; direct in vivo PK studies are limited. UCSF924 is a D4 receptor probe. Pharmacokinetic properties (t½, Cmax, F%) in rodents are not publicly reported for this specific compound. As a potent GPCR ligand, it is likely to cross the blood-brain barrier (BBB) due to its moderate lipophilicity and small molecular weight (322.4 Da).
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| ADME/Pharmacokinetics |
UCSF924 is a chemical probe and not a clinical candidate. Toxicity data for UCSF924 are limited to in vitro safety panels and acute tolerability studies in rodents. In a 7-day exploratory study in mice (oral dosing up to 30 mg/kg/day), no significant adverse effects (mortality, body weight loss, behavioral changes) were observed. No hERG inhibition or CYP450 inhibition was reported at concentrations up to 10 microM.
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| Toxicity/Toxicokinetics |
UCSF924 is a highly selective chemical probe for the D4 receptor. The D4 receptor is a drug target of interest for neuropsychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD), schizophrenia, and substance use disorders. UCSF924, along with its control UCSF924NC, is part of the NIH Molecular Libraries Program and is used to deconvolute D4 receptor biology. Biased agonism (functional selectivity) is a major theme in GPCR drug discovery, as it may yield drugs with fewer side effects (e.g., avoiding Galphai-mediated sedation while retaining beneficial arrestin-mediated effects). UCSF924 is not an FDA-approved drug.
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| References |
| Molecular Formula |
C20H22N2O2
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|---|---|
| Molecular Weight |
322.400885105133
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| Exact Mass |
322.168
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| CAS # |
1434515-70-4
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| PubChem CID |
72901200
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| Appearance |
White to off-white solid powder
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| LogP |
3.3
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
24
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| Complexity |
443
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=CC2=C(C=C1)NC(=CC2=O)CNCCCOC3=CC=CC=C3
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| InChi Key |
RPHDOVLXDYWDGF-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H22N2O2/c1-15-8-9-19-18(12-15)20(23)13-16(22-19)14-21-10-5-11-24-17-6-3-2-4-7-17/h2-4,6-9,12-13,21H,5,10-11,14H2,1H3,(H,22,23)
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| Chemical Name |
6-methyl-2-[(3-phenoxypropylamino)methyl]-1H-quinolin-4-one
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| Synonyms |
UCSF924; UCSF-924
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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 (~155.09 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.75 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 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.75 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 25.0 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: ≥ 2.5 mg/mL (7.75 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 | 3.1017 mL | 15.5087 mL | 31.0174 mL | |
| 5 mM | 0.6203 mL | 3.1017 mL | 6.2035 mL | |
| 10 mM | 0.3102 mL | 1.5509 mL | 3.1017 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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