L 741742
Based on 1 Customer Validation
L 741742 is a highly selective and brain-penetrant D4 dopamine receptor antagonist, with Ki values of 3.5 nM, 770 nM and >1700 nM for human D4, D3 and D2 receptors, respectively. L 741742 suppresses PDGFRβ, ERK1/2, and mTOR signaling pathways, and impairs autophagic flux while disrupting lysosomal function.L 741742 induces G0/G1 cell-cycle arrest and apoptosis, promotes neuronal differentiation of normal human neural stem cells, selectively inhibits growth and clonogenic potential of glioblastoma neural stem cells and primary glioblastoma tumor cells, exerts synergistic effects with Temozolomide (TMZ) (HY-17364) against glioblastoma neural stem cells in vitro, and inhibits glioblastoma neural stem cell xenograft growth in immunocompromised mice. L 741742 can be used for the research of schizophrenia and glioblastoma.
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- Pureté: 99.28%
- CAS No.: 156337-32-5
- Formule: C23H25ClN2O
- Masse moléculaire:380.91
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Stockage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Activité biologique
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Chemical Information
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Solvant et solubilité
- Pureté et documentation
- Références
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Help & FAQs
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Activité biologique
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Human D4 Receptor 3.5 nM (Ki) |
Human D3 Receptor 770 nM (Ki) |
Human D2 Receptor >1500 nM (Ki) |
L 741742 (compound 36) is a high-affinity, selective antagonist for hD4 receptors with a Ki of 3.5 nM, >500-fold selectivity over hD2 receptors, and >200-fold selectivity over hD3 receptors[1].
L 741742 (1.5-6.2 μM; 5 days) selectively inhibits the growth of patient-derived glioblastoma neural stem cells (GNS) with an IC50 of 1.5-6.2 μM and shows minimal activity against non-neural stem cell lines[2].
L 741742 (10 μM; 14 days) potently reduces the clonogenic potential of freshly isolated patient-derived glioblastoma tumor cells by 40- to 83-fold[3].
L 741742 (3 weeks) promotes neuronal differentiation of normal human neural stem cells, as indicated by increased VGlut1 expression[2].
L 741742 (10 μM; 48 hr) induces massive accumulation of autophagosomes in G411 and G362 glioblastoma neural stem cells, as shown by increased LC3B-II levels and LC3B+ puncta[2].
L 741742 (10 μM; 48 hr) impairs autophagic flux in G411 glioblastoma neural stem cells, as indicated by blocked LC3B-II turnover in the presence of Chloroquine (HY-17589A)[2].
L 741742 (10 μM) inhibits the PDGFRβ-ERK1/2 and mTOR signaling pathways in glioblastoma neural stem cells, as shown by reduced phosphorylation of ERK1/2, PDGFRβ, and S6[2].
L 741742 (10 μM; 48 hr) induces G0/G1 cell cycle arrest and subsequent apoptosis in G411 and G362 glioblastoma neural stem cells[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:GNS lines (G411, G362)
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Concentration:10 μM
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Incubation Time:2 hr; 24 hr; 48 hr
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Result:Increased LC3B-II levels (a marker of autophagosome formation) at 48 hr.
Induced LC3B+ puncta in >50% of cells at 48 hr, with a significant increase in the percentage of LC3B+ cells compared with controls.
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Cell Line:G411 GNS cells
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Concentration:10 μM
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Incubation Time:48 hr
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Result:Increased LC3B-II levels when administered alone, but did not increase LC3B-II levels in the presence of chloroquine, confirming impaired autophagic flux.
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Cell Line:GNS lines (G362, G411), normal NS, fibroblasts
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Concentration:10 μM
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Incubation Time:2 hr; 24 hr; 48 hr
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Result:Decreased phosphorylation of ERK1/2 over time in GNS (but not in NS or fibroblasts).
Decreased phosphorylation of PDGFRβ at 48 hr.
Decreased phosphorylation of S6 (a downstream mTOR effector) at 48 hr.
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Cell Line:GNS lines (G411, G362)
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Concentration:10 μM
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Incubation Time:48 hr
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Result:Induced G0/G1 phase arrest, with G411 cells showing a shift from 74.7% G1 (control) to 92.2% G1.
Increased caspase 3/7 activity.
Induced cleaved PARP expression at 48 hr.
| Species | Dose | Route | F | T1/2 |
|---|---|---|---|---|
| Rat[2] | 3 mg/kg | p.o. | 38 % | 2 h |
L 741742 (25 mg/kg; i.p.; 5 days on, 2 days off; 2 weeks) provides a significant survival benefit in mice with intracranial glioblastoma xenografts[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NOD scid gamma (NSG) (female)[2]
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Dosage:20 mg/kg
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Administration:i.p.; 5 days on, 2 days off; until study endpoint
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Result:Reduced endpoint tumor volumes.
Reduced average tumor weight by 40.9% relative to controls.
Reduced the frequency of sphere-forming (stem-like) cells to 1 in 75.6.
Increased levels of p62, ubiquitinated protein conjugates, and LC3-positive cells, confirming impaired autophagic flux in vivo.
Chemical Information
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CAS No. 156337-32-5
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Appearance Solid
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Masse moléculaire 380.91
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Formule C23H25ClN2O
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SMILES
CC1=C(C2=CC=C(Cl)C=C2)ON=C1C3CCN(CCC4=CC=CC=C4)CC3
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvant et solubilité
DMSO : 20 mg/mL (52.51 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2 mg/mL (5.25 mM); Suspended solution
This protocol yields a suspended solution of ≥ 2 mg/mL (saturation unknown). Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2 mg/mL (5.25 mM); Suspended solution
This protocol yields a suspended solution of ≥ 2 mg/mL (saturation unknown). Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Pureté et documentation
Références
[1]. Rowley M, et al. 4-Heterocyclylpiperidines as selective high-affinity ligands at the human dopamine D4 receptor. J Med Chem. 1997;40(15):2374-2385. [Content Brief]
[2]. Dolma S, et al. Inhibition of Dopamine Receptor D4 Impedes Autophagic Flux, Proliferation, and Survival of Glioblastoma Stem Cells. Cancer Cell. 2016;29(6):859-873. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.6253 mL | 13.1265 mL | 26.2529 mL | 65.6323 mL |
| 5 mM | 0.5251 mL | 2.6253 mL | 5.2506 mL | 13.1265 mL | |
| 10 mM | 0.2625 mL | 1.3126 mL | 2.6253 mL | 6.5632 mL | |
| 15 mM | 0.1750 mL | 0.8751 mL | 1.7502 mL | 4.3755 mL | |
| 20 mM | 0.1313 mL | 0.6563 mL | 1.3126 mL | 3.2816 mL | |
| 25 mM | 0.1050 mL | 0.5251 mL | 1.0501 mL | 2.6253 mL | |
| 30 mM | 0.0875 mL | 0.4375 mL | 0.8751 mL | 2.1877 mL | |
| 40 mM | 0.0656 mL | 0.3282 mL | 0.6563 mL | 1.6408 mL | |
| 50 mM | 0.0525 mL | 0.2625 mL | 0.5251 mL | 1.3126 mL |
L 741742 Related Classifications
HY-101349 Related Classifications
Powered by Bioz
- L 741742
- 156337-32-5
- L741742
- L-741742
- Dopamine Receptor
- Apoptosis
- Autophagy
- PDGFR
- ERK
- mTOR
- dopamine D4 receptor
- ERK1/2
- 5HT1A receptors
- glioblastoma neural stem cells
- human dopamine D4 receptor-expressing cells
- schizophrenia
- 5HT2 receptors
- mTOR signaling pathways
- primary glioblastoma tumor cells
- PDGFRβ
- Inhibitor
- inhibitor
- inhibit