Biological Activity

Bioactivity / Mechanism

L-741626 is a D2-preferring dopamine receptor antagonist. In one human receptor panel, reported Ki values were 11.2 ± 0.8 nM at D2L, 163 ± 32 nM at D3 and 1520 ± 280 nM at D4 (mean ± SEM). Its selectivity is relative rather than exclusive. [1]

Literature-reported observations and conditions; not Adooq-tested protocols or general treatment recommendations.

In Vitro Studies

In CHO cells expressing human dopamine receptors, L-741626 inhibited quinpirole-stimulated mitogenesis with reported EC50 values of 4.46 ± 0.9 nM at D2 and 90.4 ± 15 nM at D3 (mean ± SEM). These are functional assay endpoints, not treatment-dose recommendations. [1]

In Huh7, HepG2 and Hep3B liver cancer cell models, representative images showed reduced Ki-67 staining after 10 μM L-741626 for 48 h relative to DMSO controls. This qualitative observation does not identify the responsible molecular target. [2]

Human D2-family receptor binding selectivity

Biochemical assay · HEK 293 cells transfected with human D2L, D3 or D4 dopamine receptors [1]

The parent ligand had higher affinity for D2L than D3 or D4 in the same radioligand competition panel.

Measured endpoints — not treatment concentrations
Endpoint	Reported result	Reference
Competition binding at human D2L	Ki (mean ± SEM) 11.2 ± 0.8 nM	[1]
Competition binding at human D3	Ki (mean ± SEM) 163 ± 32 nM	[1]
Competition binding at human D4	Ki (mean ± SEM) 1520 ± 280 nM	[1]
Relative receptor binding selectivity	reported Ki ratios D3/D2 = 15; D4/D2 = 136	[1]

Literature-Reported Treatment Conditions

Method: [125I]IABN competition binding
Reported limits: Parent-compound concentration range, incubation time, vehicle, replicate n and detailed nonspecific-binding control are not specified in the reported Table 1 assay description; no such conditions are supplied here.

Methods and source locations

Compound reported in the paper: L-741626; Compound label in the paper: Compound 1 (L741,626)

Supports relative D2 preference in this assay, not exclusive receptor specificity or Adooq material validation.

Table 1, row 1 (L741,626), column headings and footnote a; receptor-testing paragraph; Figure 1

Competition binding at human D2L: [125I]IABN competition in receptor-transfected HEK 293 preparations; values are affinities, not treatment concentrations. — Table 1, row 1 (L741,626), column headings and footnote a; receptor-testing paragraph; Figure 1

Competition binding at human D3: [125I]IABN competition in receptor-transfected HEK 293 preparations; values are affinities, not treatment concentrations. — Table 1, row 1 (L741,626), column headings and footnote a; receptor-testing paragraph; Figure 1

Competition binding at human D4: [125I]IABN competition in receptor-transfected HEK 293 preparations; values are affinities, not treatment concentrations. — Table 1, row 1 (L741,626), column headings and footnote a; receptor-testing paragraph; Figure 1

Relative receptor binding selectivity: Ratios as printed in Table 1; no recalculation or cross-paper potency averaging. — Table 1, row 1 (L741,626), column headings and footnote a; receptor-testing paragraph; Figure 1

Functional antagonism of quinpirole-stimulated mitogenesis

Cell-based study · CHO cells expressing human D2 or D3 dopamine receptors [1]

L741,626 inhibited agonist-stimulated mitogenesis, with lower reported EC50 at D2 than D3.

Measured endpoints — not treatment concentrations
Endpoint	Reported result	Reference
Inhibition of quinpirole-stimulated mitogenesis through human D2 receptors	EC50 (mean ± SEM) 4.46 ± 0.9 nM	[1]
Inhibition of quinpirole-stimulated mitogenesis through human D3 receptors	EC50 (mean ± SEM) 90.4 ± 15 nM	[1]

Literature-Reported Treatment Conditions

Method: Inhibition of quinpirole-stimulated mitogenesis
Co-treatment: Quinpirole challenge; not a single-agent antiproliferation assay.
Reported limits: Quinpirole concentration, exposure duration, vehicle, parent-ligand concentration range and n are not specified in Table 1/footnote b or the assay paragraph.

Methods and source locations

Compound reported in the paper: L-741626; Compound label in the paper: Compound 1 (L741,626)

Functional antagonist potency is assay-specific; EC50 does not specify a recommended cellular treatment dose.

Table 1, row 1 (L741,626), D2/D3 function columns and footnote b; receptor-testing paragraph

Inhibition of quinpirole-stimulated mitogenesis through human D2 receptors: Functional antagonist assay in receptor-transfected CHO cells; endpoint named EC50 by the authors. — Table 1, row 1 (L741,626), D2/D3 function columns and footnote b; receptor-testing paragraph

Inhibition of quinpirole-stimulated mitogenesis through human D3 receptors: Same reported CHO functional panel; quinpirole is the agonist challenge. — Table 1, row 1 (L741,626), D2/D3 function columns and footnote b; receptor-testing paragraph

Ki-67 staining in liver cancer cell models

Cell-based study · Huh7, HepG2 and Hep3B liver cancer cell lines [2]

The published representative images show reduced Ki-67 staining after L-741626 treatment versus DMSO.

Measured endpoints — not treatment concentrations
Endpoint	Reported result	Reference
Ki-67 immunofluorescence in Huh7, HepG2 and Hep3B cells	Qualitative staining change Reduced Ki-67 staining in the representative L-741626-treated images relative to DMSO controls; 10 μM, 48 h; scale bar 100 μm.	[2]

Literature-Reported Treatment Conditions

Treatment concentration: 10 μM
Exposure duration: 48 h
Method: Cell treatment followed by Ki-67 immunofluorescence.
Vehicle: DMSO control, as explicitly stated in Figure 1C caption.
Reported limits: DMSO percentage and independent replicate n for panel C are not specified in the caption/read assay methods. Panel C has no quantitative Ki-67 effect estimate; none is supplied.

Methods and source locations

Compound reported in the paper: L-741626; Compound label in the paper: L-741626

Qualitative cellular phenotype only; this experiment does not demonstrate D2 dependence, direct Ref-1 binding, or clinical antitumor efficacy.

Figure 1C and caption; Materials and methods Cell line culture and shRNAs, Reagents and antibodies; Results L-741626 inhibits the growth of HCC cells

Ki-67 immunofluorescence in Huh7, HepG2 and Hep3B cells: Figure 1C Ki-67 immunofluorescence; no exact fraction or effect size taken from images. — Figure 1C and caption; Materials and methods Cell line culture and shRNAs, Reagents and antibodies; Results L-741626 inhibits the growth of HCC cells

In Vivo Studies

L-741626 suppressed mouse locomotor activity at higher doses, including a significant effect at 30.0 mg/kg in D2-receptor knockout mice. In separate agonist-challenge tests, it failed to reverse locomotor suppression caused by quinpirole, 7-OH-DPAT or PD 128907. These findings limit receptor-specific interpretation of this behavioral endpoint. [3]

Locomotor suppression and a D2-knockout specificity control

Animal study · Swiss–Webster mice and D2-receptor wild-type/knockout mice [3]

L-741626 decreased locomotion at higher doses; the 30.0 mg/kg response remained significant in D2-knockout mice, limiting attribution of this endpoint exclusively to D2 blockade.

Measured endpoints — not treatment concentrations
Endpoint	Reported result	Reference
Swiss–Webster mice horizontal locomotor activity	Mean counts ± SEM Vehicle: 3820 ± 718; 3.0 mg/kg: 3680 ± 556; 10.0 mg/kg: 1891 ± 139; 30.0 mg/kg: 379 ± 64.0 counts/60 min (mean ± SEM); n = 6 subjects per dose. 10.0 mg/kg: P < 0.05; 30.0 mg/kg: P < 0.01 versus vehicle.	[3]
Dopamine D2-receptor wild-type mice horizontal locomotor activity	Mean counts ± SEM Vehicle: 5650 ± 1030; 3.0 mg/kg: 7510 ± 1470; 10.0 mg/kg: 4810 ± 886; 30.0 mg/kg: 735 ± 119 counts/60 min (mean ± SEM); n = 6 subjects per dose. 30.0 mg/kg: P < 0.01 versus vehicle.	[3]
Dopamine D2-receptor knockout mice horizontal locomotor activity	Mean counts ± SEM Vehicle: 2120 ± 460; 3.0 mg/kg: 2440 ± 747; 10.0 mg/kg: 2290 ± 489; 30.0 mg/kg: 660 ± 97.6 counts/60 min (mean ± SEM); n = 6 subjects per dose. 30.0 mg/kg: P < 0.01 versus vehicle.	[3]

Conditions shared by the study groups

Route: Intraperitoneal
Frequency: Acute test; mutant mice could be tested at multiple doses with at least 48 h between exposures.
Treatment course: 60-min behavioral observation
Vehicle: Saline-based L-741626 solution adjusted with acetic acid and NaOH to pH 5–7.

Study groups and reported outcomes
Group / dose	Comparator	Observed result	Reference
Swiss–Webster mice 3.0, 10.0 or 30.0 mg/kg	Vehicle-treated mice of the same line.	Vehicle: 3820 ± 718; 3.0 mg/kg: 3680 ± 556; 10.0 mg/kg: 1891 ± 139; 30.0 mg/kg: 379 ± 64.0 counts/60 min (mean ± SEM); n = 6 subjects per dose. 10.0 mg/kg: P < 0.05; 30.0 mg/kg: P < 0.01 versus vehicle.	[3]
Dopamine D2-receptor wild-type mice 3.0, 10.0 or 30.0 mg/kg	Vehicle-treated mice of the same line.	Vehicle: 5650 ± 1030; 3.0 mg/kg: 7510 ± 1470; 10.0 mg/kg: 4810 ± 886; 30.0 mg/kg: 735 ± 119 counts/60 min (mean ± SEM); n = 6 subjects per dose. 30.0 mg/kg: P < 0.01 versus vehicle.	[3]
Dopamine D2-receptor knockout mice 3.0, 10.0 or 30.0 mg/kg	Vehicle-treated mice of the same line.	Vehicle: 2120 ± 460; 3.0 mg/kg: 2440 ± 747; 10.0 mg/kg: 2290 ± 489; 30.0 mg/kg: 660 ± 97.6 counts/60 min (mean ± SEM); n = 6 subjects per dose. 30.0 mg/kg: P < 0.01 versus vehicle.	[3]

Swiss–Webster mice: Model: Swiss–Webster mice; Reported limits: Sex and age not specified in the Subjects section; randomization and blinding for locomotion not specified there. Exact vehicle matching of pH-adjustment constituents is not detailed.

Dopamine D2-receptor wild-type mice: Model: Dopamine D2-receptor wild-type mice; Reported limits: Sex and age not specified in the Subjects section; randomization and blinding for locomotion not specified there. Exact vehicle matching of pH-adjustment constituents is not detailed.

Dopamine D2-receptor knockout mice: Model: Dopamine D2-receptor knockout mice; Reported limits: Sex and age not specified in the Subjects section; randomization and blinding for locomotion not specified there. Exact vehicle matching of pH-adjustment constituents is not detailed.

Methods and source locations

Compound reported in the paper: L-741626; Compound label in the paper: L-741626

Describes acute mouse behavioral activity and its receptor-specificity limit, not therapeutic efficacy.

Table 3 with footnotes; Figure 5 and caption; Methods Subjects, Procedures, Drugs and Statistics; Discussion final antagonist-selectivity paragraph

Swiss–Webster mice horizontal locomotor activity: Infrared beam interruptions; Table 3 dose comparisons and Dunnett test. — Table 3 with footnotes; Figure 5 and caption; Methods Subjects, Procedures, Drugs and Statistics; Discussion final antagonist-selectivity paragraph

Dopamine D2-receptor wild-type mice horizontal locomotor activity: Infrared beam interruptions; Table 3 dose comparisons and Dunnett test. — Table 3 with footnotes; Figure 5 and caption; Methods Subjects, Procedures, Drugs and Statistics; Discussion final antagonist-selectivity paragraph

Dopamine D2-receptor knockout mice horizontal locomotor activity: Infrared beam interruptions; Table 3 dose comparisons and Dunnett test. — Table 3 with footnotes; Figure 5 and caption; Methods Subjects, Procedures, Drugs and Statistics; Discussion final antagonist-selectivity paragraph

Swiss–Webster mice · Table 3 with footnotes; Figure 5 and caption; Methods Subjects, Procedures, Drugs and Statistics; Discussion final antagonist-selectivity paragraph

Dopamine D2-receptor wild-type mice · Table 3 with footnotes; Figure 5 and caption; Methods Subjects, Procedures, Drugs and Statistics; Discussion final antagonist-selectivity paragraph

Dopamine D2-receptor knockout mice · Table 3 with footnotes; Figure 5 and caption; Methods Subjects, Procedures, Drugs and Statistics; Discussion final antagonist-selectivity paragraph

Failure to reverse agonist-induced locomotor suppression

Animal study · Swiss–Webster mice challenged with quinpirole, 7-OH-DPAT or PD 128907 [3]

In this locomotor endpoint, L-741626 pretreatment failed to produce the expected functional reversal of agonist-induced suppression.

Measured endpoints — not treatment concentrations
Endpoint	Reported result	Reference
Reversal of dopamine-agonist-induced locomotor suppression	Qualitative interaction outcome L-741626 did not reverse the locomotor decreases caused by quinpirole, 7-OH-DPAT or PD 128907; the authors report added locomotor suppression.	[3]

Conditions shared by the study groups

Route: L-741626 intraperitoneally; agonist subcutaneously.
Frequency: Acute interaction test: L-741626 30 min before the agonist injection.
Treatment course: 60-min activity observation immediately after the second injection, following chamber habituation.
Vehicle: L-741626 dissolved in saline with acetic acid; pH adjusted to 5–7 with NaOH. Agonist dissolved in saline.

Study groups and reported outcomes
Group / dose	Comparator	Observed result	Reference
quinpirole challenge with L-741626 pretreatment L-741626: 3.0, 10.0 or 30.0 mg/kg; quinpirole: 0.03, 0.1 or 0.3 mg/kg as displayed in Figure 6a.	Agonist plus vehicle at the same agonist dose; vehicle plus vehicle baseline (V).	L-741626 shifted the quinpirole locomotor dose-effect curve downward, adding suppression rather than reversing it. Figure 6 reports mean activity counts ± SEM with six to nine mice per dose; no exact counts or dose-specific effect sizes extracted from the graph.	[3]
7-OH-DPAT challenge with L-741626 pretreatment L-741626: 3.0, 10.0 or 30.0 mg/kg; 7-OH-DPAT: 0.03, 0.1 or 0.3 mg/kg as displayed in Figure 6b.	Agonist plus vehicle at the same agonist dose; vehicle plus vehicle baseline (V).	L-741626 shifted the 7-OH-DPAT locomotor dose-effect curve downward, adding suppression rather than reversing it. Figure 6 reports mean activity counts ± SEM with six to nine mice per dose; no exact counts or dose-specific effect sizes extracted from the graph.	[3]
PD 128907 challenge with L-741626 pretreatment L-741626: 3.0, 10.0 or 30.0 mg/kg; PD 128907: 0.03, 0.1 or 0.3 mg/kg as displayed in Figure 6c.	Agonist plus vehicle at the same agonist dose; vehicle plus vehicle baseline (V).	L-741626 shifted the PD 128907 locomotor dose-effect curve downward, adding suppression rather than reversing it. Figure 6 reports mean activity counts ± SEM with six to nine mice per dose; no exact counts or dose-specific effect sizes extracted from the graph.	[3]

quinpirole challenge with L-741626 pretreatment: Model: Swiss–Webster mice; Reported limits: Sex and age, locomotion randomization/blinding and exact per-group n are not specified in the located text/caption. Exact matching of acid/base vehicle constituents is not detailed. Only agonist doses displayed in Figure 6 are represented.

7-OH-DPAT challenge with L-741626 pretreatment: Model: Swiss–Webster mice; Reported limits: Sex and age, locomotion randomization/blinding and exact per-group n are not specified in the located text/caption. Exact matching of acid/base vehicle constituents is not detailed. Only agonist doses displayed in Figure 6 are represented.

PD 128907 challenge with L-741626 pretreatment: Model: Swiss–Webster mice; Reported limits: Sex and age, locomotion randomization/blinding and exact per-group n are not specified in the located text/caption. Exact matching of acid/base vehicle constituents is not detailed. Only agonist doses displayed in Figure 6 are represented.

Methods and source locations

Compound reported in the paper: L-741626; Compound label in the paper: L-741626

Negative interaction evidence in a specific behavioral assay; does not invalidate receptor binding or establish absence of all D2 antagonism.

Figure 6a–c and caption; Results Effects of DA antagonists alone and in combination; Methods Procedures and Drugs; Discussion paragraph beginning None of the antagonists

Reversal of dopamine-agonist-induced locomotor suppression: Agonist dose-response tests with vehicle or L-741626 pretreatment; 60-min automated activity counts; Figure 6, six to nine mice per dose. — Figure 6a–c and caption; Results Effects of DA antagonists alone and in combination; Methods Procedures and Drugs; Discussion paragraph beginning None of the antagonists

quinpirole challenge with L-741626 pretreatment · Figure 6a, caption and shared legend; Results P26; Methods Subjects P7, Procedures P9-P10 and Drugs P11; Discussion P33

7-OH-DPAT challenge with L-741626 pretreatment · Figure 6b, caption and shared legend; Results P26; Methods Subjects P7, Procedures P9-P10 and Drugs P11; Discussion P33

PD 128907 challenge with L-741626 pretreatment · Figure 6c, caption and shared legend; Results P26; Methods Subjects P7, Procedures P9-P10 and Drugs P11; Discussion P33

Specifications

Manufacturer	Adooq Bioscience
Actions	Antagonist
CAS Number	81226-60-0
Applications	D2 dopamine receptor antagonist
Formula	C₂₀H₂₁ClN₂O
Molecular Weight	340.85
Synonyms	L-741,626
SMILES	C1CN(CCC1(C2=CC=C(C=C2)Cl)O)CC3=CNC4=CC=CC=C43

Storage & Solubility

In Vitro Solubility

Reported Solubility

No reported solubility data are available for this product.

Preparing Stock Solutions

Stock preparation is unavailable for this product molecular weight.

Calculated stock concentrations do not establish solvent solubility. Refer to the reported solubility data for experimental guidance.

Storage

Store powder at -20°C, keep desiccated.
In powder form, the chemical is stable for 36 months.
In solution, store at -20°C and use within 1 month to prevent loss of potency. Aliquot to avoid multiple freeze/thaw cycles.

Research References

[1] Peter Grundt, Sarah Little Jane Husbands, Robert R. Luedtke, et al. Analogues of the dopamine D2 receptor antagonist L741,626: Binding, function, and SAR. Bioorganic & medicinal chemistry letters (2007). PMID: 17095222 DOI: 10.1016/j.bmcl.2006.10.076 Source material
[2] Jin S, Zhao Q, Sun X, et al. L-741626 inhibits hepatocellular carcinoma progression by targeting Ref-1 to suppress MAPK/ERK signalling pathway activity. Biology direct (2025). PMID: 40241114 DOI: 10.1186/s13062-025-00624-z Source material
[3] Li SM, Collins GT, Paul NM, et al. Yawning and locomotor behavior induced by dopamine receptor agonists in mice and rats. Behavioural pharmacology (2010). PMID: 20463460 DOI: 10.1097/fbp.0b013e32833a5c68 Source material

Publications

1 publication citing this product

Yoon-Jin Kim, .et al. , Sci Adv, 2021, Feb 19;7(8) PMID: 33608268

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L-741626

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Biological Activity

Bioactivity / Mechanism

In Vitro Studies

Human D2-family receptor binding selectivity

Literature-Reported Treatment Conditions

Functional antagonism of quinpirole-stimulated mitogenesis

Literature-Reported Treatment Conditions

Ki-67 staining in liver cancer cell models

Literature-Reported Treatment Conditions

In Vivo Studies

Locomotor suppression and a D2-knockout specificity control

Conditions shared by the study groups

Failure to reverse agonist-induced locomotor suppression

Conditions shared by the study groups

Specifications

Storage & Solubility

In Vitro Solubility

Reported Solubility

Preparing Stock Solutions

Storage

Research References

Publications

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