| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
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| Targets |
L-745870 targets the dopamine D4 receptor, a G protein-coupled receptor that is involved in the regulation of cognition, attention, and reward. It acts as a potent and selective antagonist, with a Ki of 0.43 nM for the D4 receptor. The compound shows selectivity for D4 over other dopamine receptor subtypes and other targets, including D2 receptors, 5-HT2 receptors, and α-adrenoceptors.
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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].
In vitro, L-745870 selectively binds to the D4 receptor with high affinity (Ki = 0.43 nM). The compound inhibits D4 receptor-mediated signaling, as measured by cAMP accumulation or other downstream readouts. L-745870 shows selectivity for D4 over D2 receptors, 5-HT2 receptors, and α-adrenoceptors. The compound's high potency and selectivity make it a valuable tool for studying D4 receptor pharmacology. |
| ln Vivo |
L-745870 exhibits favorable pharmacokinetic characteristics in both rats and monkeys, with great brain penetration in rats and a high brain-to-plasma ratio (oral bioavailability of 20–60% and plasma t1/2 of 2.1–2.8 hours)[2]. 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 [2].
In vivo, L-745870 has antipsychotic effects in animal models. The compound is brain-penetrant and orally active, with favorable pharmacokinetic characteristics in both rats and monkeys. L-745870 has been studied in models of schizophrenia and other psychiatric disorders. However, despite its efficacy in animal models, L-745870 was not effective in human trials. The compound exhibits great brain penetration. |
| Enzyme Assay |
The non-cellular assay for L-745870 involves measuring its binding affinity for the D4 receptor using radioligand binding assays. Membrane preparations from cells expressing the D4 receptor are incubated with a radiolabeled D4 receptor ligand (such as [³H]-spiperone) and varying concentrations of L-745870. The inhibition of radioligand binding is measured, and the Ki is determined from competition curves.
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| Cell Assay |
The cellular assay for L-745870 involves treating cells expressing the D4 receptor with the compound and measuring its effects on receptor-mediated signaling. Cells are pre-incubated with L-745870, and the inhibition of agonist-induced cAMP accumulation is measured using a competitive immunoassay. The IC50 is determined from concentration-response curves. The selectivity profile is confirmed by testing the compound against other receptors, including D2, 5-HT2, and α-adrenoceptors.
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| Animal Protocol |
In the in vivo efficacy study, L-745870 is administered orally to rodent models of schizophrenia. Behavioral assessments, such as locomotor activity, prepulse inhibition, and conditioned avoidance response, are performed to evaluate the compound's antipsychotic effects. Pharmacokinetic studies are conducted in rats and monkeys to assess brain penetration and systemic exposure.
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| ADME/Pharmacokinetics |
L-745870 has a molecular weight of 326.82 and a molecular formula of C₁₈H₁₉ClN₄. The compound is brain-penetrant and orally active. It should be stored as a powder at -25 to -15°C for up to 3 years or in solvent at -85 to -65°C for up to 2 years. The compound has a purity of ≥98%. L-745870 should be handled with appropriate laboratory safety precautions.
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| Toxicity/Toxicokinetics |
The toxicological profile of L-745870 has not been extensively characterized in the published literature. As a D4 receptor antagonist, it may have effects on cognition, attention, and reward. Comprehensive toxicology data are limited, and L-745870 is not approved for clinical use. The compound should be handled with appropriate laboratory safety precautions.
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| References |
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| Additional Infomation |
3-[[4-(4-chlorophenyl)-1-piperazinyl]methyl]-1H-pyrrolo[2,3-b]pyridine is a member of the piperazine class of compounds.
L-745870 is a potent and selective dopamine D4 receptor antagonist that has been studied as a potential antipsychotic agent. Despite showing efficacy in animal models, the compound was not effective in human trials. Its favorable pharmacokinetic characteristics and brain penetration make it a valuable research tool for studying D4 receptor function. L-745870 is not approved for clinical use and is strictly a research compound. |
| Molecular Formula |
C18H19CLN4
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|---|---|
| Molecular Weight |
326.82300
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| Exact Mass |
326.13
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| CAS # |
158985-00-3
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| Related CAS # |
L-745870 hydrochloride;1173023-36-3;L-745870 trihydrochloride;866021-03-6
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| PubChem CID |
5311200
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| Appearance |
White to off-white solid powder
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| Boiling Point |
590.8ºC at 760mmHg
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| Flash Point |
311.1ºC
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| Vapour Pressure |
3.05E-14mmHg at 25°C
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| LogP |
3.541
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
23
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| Complexity |
377
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
OGJGQVFWEPNYSB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H19ClN4/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)
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| Chemical Name |
3-[[4-(4-chlorophenyl)piperazin-1-yl]methyl]-1H-pyrrolo[2,3-b]pyridine
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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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 : ~25 mg/mL (~76.49 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.65 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 (7.65 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.0598 mL | 15.2989 mL | 30.5979 mL | |
| 5 mM | 0.6120 mL | 3.0598 mL | 6.1196 mL | |
| 10 mM | 0.3060 mL | 1.5299 mL | 3.0598 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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