| Size | Price | Stock | Qty |
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| 10mg |
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| Targets |
Dopamine D4 receptor. L-745,870 is a highly potent and selective D4 dopamine receptor antagonist with a Ki of 0.51 nM. It shows weaker affinity for D2 (Ki = 960 nM) and D3 (Ki = 2300 nM) receptors. The compound shows >1000-fold selectivity over 5-HT2, D1, and D5 receptors.
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| ln Vitro |
In transfected human embryonic kidney (HEK293) and Chinese hamster ovary (CHO) cells, L-745870 inhibits the capacity of D4 receptors to suppress agonist-induced stimulation of [35S]-GTPgS binding. It also prevents forskolin-stimulated glandular stimulation. Glycolate cyclase activity inhibition, blocking dopamine-induced suppression of the Ca2+ current in transfected GH4C1 pituitary cells, blocking D4 activation of clonal G protein-coupled inward rectifier K+ channels, and counteracting the stimulation of extracellular acidification of transfected cells caused by dopamine[1].
L-745,870 is a potent and selective D4 dopamine receptor antagonist with a Ki of 0.43 nM. It shows weaker affinity for D2 (Ki = 960 nM) and D3 (Ki = 960 nM) receptors. The compound is a selective antagonist for the dopamine D4 receptor, forming critical interactions with residues in the receptor's orthosteric pocket. It has been studied for potential therapeutic applications in schizophrenia, addiction, and Parkinson's disease. |
| ln Vivo |
L-745870 exhibits favorable pharmacokinetic characteristics in rats and monkeys, with high brain-to-plasma ratio, great brain penetration, and oral bioavailability of 20–60% and plasma t1/2 of 2.1–2.8 hours[1]. Squirrel monkeys were given 10 mg/kg p.o. of L745870 orally, which resulted in mild sedation and extrapyramidal motor symptoms, including bradykinesia, which became noticeable at 30 mg/kg. In monkeys, lower doses of L-745870 did not cause any behavioral changes [1].
In vivo, L-745,870 has been studied for its effects on dopamine D4 receptor-mediated behaviors. The compound is brain-penetrant and orally active. It has been investigated for potential therapeutic applications in schizophrenia, addiction, and Parkinson's disease. Further in vivo studies are needed to fully characterize its therapeutic potential. |
| Enzyme Assay |
In vitro receptor binding assays for L-745,870 involve measuring its affinity for dopamine D2, D3, and D4 receptors using radioligand binding techniques. Membranes from cells expressing the respective receptors are incubated with radiolabeled dopamine receptor ligands and increasing concentrations of L-745,870. Bound and free ligand are separated by filtration, and radioactivity is measured. Ki values are determined from competition binding curves.
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| Cell Assay |
In vitro cellular assays for L-745,870 involve treating cells expressing dopamine D4 receptors with the compound and measuring D4 receptor-mediated signaling, such as cAMP modulation or calcium mobilization. Cells are treated with various concentrations of L-745,870 and stimulated with a D4 receptor agonist. The compound's ability to inhibit agonist-induced responses is assessed.
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| Animal Protocol |
In vivo animal studies for L-745,870 typically involve administration to rodent models to assess its effects on D4 receptor-mediated behaviors. The compound is orally active and brain-penetrant. Efficacy is assessed by measuring behavioral changes related to schizophrenia, addiction, or Parkinson's disease. The compound has been studied in various preclinical models.
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| ADME/Pharmacokinetics |
L-745,870 trihydrochloride is brain-penetrant and orally active. It has a molecular weight of 441.18 and is soluble in water (<43.62 mg/mL). The compound is a potent and selective D4 dopamine receptor antagonist. Further pharmacokinetic studies are needed to fully characterize its profile.
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| Toxicity/Toxicokinetics |
Preclinical toxicity studies of L-745,870 are limited. The compound is a potent and selective D4 dopamine receptor antagonist that has been studied for potential therapeutic applications in schizophrenia, addiction, and Parkinson's disease. Comprehensive toxicological evaluation is needed before clinical development.
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| References |
[1]. Bristow LJ, et al. Schizophrenia and L-745,870, a novel dopamine D4 receptor antagonist. Trends Pharmacol Sci. 1997 Jun;18(6):186-8.
[2]. Patel S, et al. Biological profile of L-745,870, a selective antagonist with high affinity for the dopamine D4 receptor. J Pharmacol Exp Ther. 1997 Nov;283(2):636-47. [3]. Kulagowski JJ, et al. 3-((4-(4-Chlorophenyl)piperazin-1-yl)-methyl)-1H-pyrrolo-2,3-b-pyridine: an antagonist with high affinity and selectivity for the human dopamine D4 receptor. J Med Chem. 1996 May 10;39(10):1941-2. |
| Additional Infomation |
L-745,870 Trihydrochloride is a highly potent and selective dopamine D4 receptor antagonist with a Ki of 0.51 nM for D4, showing >1000-fold selectivity over 5-HT2, D1, and D5 receptors. It is brain-penetrant and orally active. L-745,870 has been studied for potential therapeutic applications in schizophrenia, addiction, and Parkinson's disease. It is a valuable research tool for studying D4 receptor function.
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| Molecular Formula |
C18H19N4CL.3[HCL]
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| Molecular Weight |
436.20608
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| Exact Mass |
362.107
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| CAS # |
866021-03-6
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| Related CAS # |
L-745870;158985-00-3;L-745870 hydrochloride;1173023-36-3
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| PubChem CID |
49759035
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
4.343
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
26
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| Complexity |
377
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| Defined Atom Stereocenter Count |
0
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| SMILES |
Cl.ClC1C=CC(N2CCN(CC3C4C(=NC=CC=4)NC=3)CC2)=CC=1
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| InChi Key |
KJSOYZLYCFYXFC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H19ClN4.3ClH/c19-15-3-5-16(6-4-15)23-10-8-22(9-11-23)13-14-12-21-18-17(14)2-1-7-20-18;;;/h1-7,12H,8-11,13H2,(H,20,21);3*1H
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| Chemical Name |
3-[[4-(4-chlorophenyl)piperazin-1-yl]methyl]-1H-pyrrolo[2,3-b]pyridine;trihydrochloride
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2925 mL | 11.4624 mL | 22.9247 mL | |
| 5 mM | 0.4585 mL | 2.2925 mL | 4.5849 mL | |
| 10 mM | 0.2292 mL | 1.1462 mL | 2.2925 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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