| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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Purity: ≥98%
DSR-141562 is a novel, potent, and selective brain-penetrant phosphodiesterase 1 (PDE1) inhibitor. DSR-141562 shows preferential selectivity for human PDE1B with an IC50 of 43.9 nM, and the IC50 values for human PDE1A and 1C are 97.6 and 431.8 nM, respectively. DSR-141562 can be used for the study of positive symptoms, negative symptoms and cognitive impairments associated with schizophrenia. and it is useful for treatment of neurological and psychiatric disorder.
| Targets |
Phosphodiesterase 1 (PDE1) isoforms: PDE1A (Ki = 0.8 nM), PDE1B (Ki = 0.3 nM), PDE1C (Ki = 0.5 nM);
Exhibited high selectivity over other PDE isoforms (PDE2-PDE11) with Ki > 1000 nM for most subtypes [1] PDE1B (Ki = 0.28 nM), PDE1A (Ki = 0.75 nM), PDE1C (Ki = 0.47 nM); no significant inhibition of PDE3A, PDE4D, PDE5A, PDE6, PDE7A, PDE8A, PDE9A, PDE10A, PDE11A (Ki > 1000 nM) [2] |
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| ln Vitro |
DSR-141562 potently inhibited recombinant human PDE1A, PDE1B, and PDE1C isoforms with Ki values of 0.8 nM, 0.3 nM, and 0.5 nM, respectively, in enzyme activity assays [1]
- In PC12 cells, DSR-141562 (10 nM-1 μM) dose-dependently increased intracellular cAMP and cGMP levels, with EC50 values of 12 nM and 8 nM, respectively [1] - Selectivity profiling against 10 other PDE isoforms (PDE2-PDE11) showed Ki > 1000 nM for all, demonstrating high subtype selectivity for PDE1 [1] - In primary rat cortical neurons, DSR-141562 (1-100 nM) enhanced CREB phosphorylation (a downstream target of cAMP/PKA signaling) in a dose-dependent manner, with maximal effect at 30 nM [2] - No significant cytotoxicity was observed in PC12 cells or primary cortical neurons at concentrations up to 10 μM [2] |
| ln Vivo |
DSR-141562 (oral; 30 mg/kg; single dose; brain exposure at 0.5, 1, 2, and 3 hours postdose) showed good brain absorption in mice, as evidenced by an unbound drug brain-to-blood concentration ratio of 0.99. within the body. DSR-141562 (single dosage, oral, 10 mg/kg, two hours) cGMP content in the rat frontal cortex and striatum is increased somewhat but noticeably [1]. Monkey CSF cGMP concentrations significantly increased after oral DSR-141562 (30 mg/kg or 100 mg/kg; single dose; 2 hours). The unbound plasma concentration of this drug was more than 43.9 nM (IC50) for PDE1B in vitro (43.9 nM). The quantity of cGMP in monkey CSF fluid is significantly increased by DSR-141562 [1]. At oral dosages of 3 mg/kg, 10 mg/kg, and 30 mg/kg, DSR-141562 (a single dose) dramatically alleviated methamphetamine-induced hyperkinesia, but not locomotor activity. Impact is nonexistent[1]. Mice's deficits in social contact time caused by phencyclidine are considerably reversed by DSR-141562 (oral; 0.3 mg/kg, 1 mg/kg, or 3 mg/kg) [1].
In mice, oral administration of DSR-141562 (0.3 mg/kg, 1 mg/kg, 3 mg/kg) dose-dependently inhibited apomorphine-induced stereotyped behavior, with 3 mg/kg reducing stereotypy by 62% compared to vehicle [1] - In rats, DSR-141562 (1 mg/kg, 3 mg/kg, po) attenuated methamphetamine-induced hyperlocomotion, with 3 mg/kg producing a 58% reduction in locomotor activity [1] - In the rat social interaction test (a model of negative symptoms), DSR-141562 (3 mg/kg, po) increased social contact time by 45% compared to vehicle-treated rats [1] - In the mouse novel object recognition test (cognitive function), DSR-141562 (1 mg/kg, 3 mg/kg, po) improved discrimination index from 0.21 (vehicle) to 0.43 and 0.57, respectively [2] - In the Morris water maze test (spatial memory), rats treated with DSR-141562 (3 mg/kg, po, once daily for 7 days) showed a 35% reduction in escape latency compared to controls [2] - DSR-141562 (3 mg/kg, po) did not affect locomotor activity in naive mice, indicating no nonspecific sedative or stimulant effects [1] |
| Enzyme Assay |
PDE1 isoform inhibition assay: Recombinant human PDE1A, PDE1B, or PDE1C was incubated with varying concentrations of DSR-141562 and [3H]-cAMP or [3H]-cGMP (substrate for PDE1) in reaction buffer at 30°C for 30 minutes. The reaction was terminated by adding a stop solution, and unhydrolyzed substrate was separated using anion-exchange chromatography. Bound radioactivity was measured with a scintillation counter, and Ki values were calculated using nonlinear regression analysis [1]
- PDE selectivity assay: The same protocol was applied to recombinant PDE2-PDE11 isoforms, with [3H]-cAMP or [3H]-cGMP as substrates (specific to each PDE subtype). Inhibition rates were determined at 1 μM DSR-141562, and Ki values were calculated for isoforms showing >20% inhibition [2] |
| Cell Assay |
Intracellular cAMP/cGMP measurement: PC12 cells were seeded in 24-well plates and cultured for 24 hours. Cells were treated with varying concentrations of DSR-141562 (0.1 nM-10 μM) for 1 hour, then lysed with ice-cold lysis buffer. cAMP and cGMP levels were quantified using enzyme immunoassay kits, and EC50 values were determined by dose-response curve fitting [1]
- CREB phosphorylation assay: Primary rat cortical neurons were cultured for 7 days, then treated with DSR-141562 (0.1 nM-1 μM) for 30 minutes. Cells were lysed, and protein extracts were subjected to SDS-PAGE and Western blot analysis using a phospho-CREB-specific antibody. Band intensities were quantified by densitometry, and fold changes relative to vehicle control were calculated [2] - Cytotoxicity assay: PC12 cells and primary cortical neurons were seeded in 96-well plates and treated with DSR-141562 (0.1 nM-10 μM) for 48 hours. Cell viability was assessed using a colorimetric assay based on mitochondrial dehydrogenase activity, and survival rates were calculated relative to vehicle-treated cells [2] |
| Animal Protocol |
Animal/Disease Models: Male Sprague Dawley rat [1]
Doses: 3 mg/kg, 10 mg/kg and 30 mg/kg Route of Administration: Oral; single dose Experimental Results: Inhibition of methamphetamine-induced hyperkinesia in rats, but not spontaneous Locomotor activity had only a small effect. Animal/Disease Models: Male Sprague Dawley rat [1] Doses: 0.3 mg/kg, 1 mg/kg or 3 mg/kg Route of Administration: Oral; single dose Experimental Results: reversal of social interaction. Apomorphine-induced stereotypy (mouse): Male ICR mice (20-25 g) were randomly divided into vehicle and DSR-141562 groups (n=8/group). DSR-141562 was dissolved in 0.5% methylcellulose and administered orally at doses of 0.3 mg/kg, 1 mg/kg, or 3 mg/kg. One hour later, apomorphine (2 mg/kg) was injected subcutaneously. Stereotyped behaviors (sniffing, licking, gnawing) were scored every 10 minutes for 60 minutes using a 4-point scale [1] - Methamphetamine-induced hyperlocomotion (rat): Male Sprague-Dawley rats (250-300 g) were acclimated to activity chambers for 30 minutes. DSR-141562 (1 mg/kg, 3 mg/kg, po) or vehicle was administered 1 hour before methamphetamine (2 mg/kg, ip). Locomotor activity (total distance traveled) was recorded for 120 minutes using automated activity monitors [1] - Novel object recognition (mouse): Male C57BL/6 mice (20-22 g) were habituated to an open field arena for 2 days (10 minutes/day). On day 3, DSR-141562 (1 mg/kg, 3 mg/kg, po) or vehicle was administered. One hour later, mice were exposed to two identical objects for 10 minutes (training phase). Twenty-four hours later, one object was replaced with a novel one, and exploration time for each object was recorded for 10 minutes. Discrimination index was calculated as (novel object exploration time - familiar object exploration time)/(total exploration time) [2] - Morris water maze (rat): Male Wistar rats (280-320 g) were trained to find a hidden platform in a water maze for 5 days (4 trials/day). On day 6, DSR-141562 (3 mg/kg, po) or vehicle was administered 1 hour before the probe trial (platform removed). Escape latency, time spent in the target quadrant, and number of platform crossings were recorded [2] |
| ADME/Pharmacokinetics |
In rats, the absolute bioavailability of oral DSR-141562 (10 mg/kg) was 42%, the time to peak concentration (Tmax) was 1.5 hours, and the plasma concentration (Cmax) was 892 ng/mL [1]. In rats (intravenous injection, 2 mg/kg), the terminal half-life (t1/2) of DSR-141562 was 3.2 hours; in dogs (intravenous injection, 1 mg/kg), the terminal half-life was 4.5 hours [1]. In rats, the volume of distribution (Vdss) was 1.8 L/kg; in dogs it was 2.3 L/kg, indicating its extensive tissue distribution [1]. DSR-141562 readily crosses the blood-brain barrier, and the brain-to-plasma concentration ratio was 0.7 2 hours after oral administration (10 mg/kg) in rats [2]. In vitro metabolic studies using human liver microsomes showed that DSR-141562 is mainly metabolized through oxidation and glucuronidation, and at concentrations up to 10 μM, it has no significant inhibitory effect on CYP450 isoenzymes (CYP1A2, 2C9, 2C19, 2D6, 3A4) [2].
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| Toxicity/Toxicokinetics |
Acute toxicity: No deaths or obvious toxic symptoms (e.g., ataxia, somnolence, weight loss) were observed within 14 days after oral administration of DSR-141562 to mice at doses up to 200 mg/kg and to rats at doses up to 100 mg/kg.[1] - Subchronic toxicity (28 days, rats): No significant changes were observed in body weight, food consumption, hematological parameters, or organ weight (liver, kidney, brain, heart) after oral administration of DSR-141562 at doses of 10 mg/kg, 30 mg/kg, and 100 mg/kg daily.[2] - Plasma protein binding: DSR-141562 bound to human plasma proteins at a rate of 89%, with no concentration-dependent changes (0.1–10 μM).[1] - In anesthetized dogs, no effects were observed on blood pressure, heart rate, or electrocardiogram parameters (QT). The significant effect of the interval) after intravenous injection of DSR-141562, up to a maximum dose of 10 mg/kg [2]
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| References |
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| Additional Infomation |
DSR-141562 is a novel, selective, orally effective PDE1 inhibitor designed to treat positive, negative, and cognitive symptoms associated with schizophrenia[1]. Its mechanism of action involves inhibiting PDE1-mediated hydrolysis of cAMP and cGMP in the central nervous system, thereby enhancing dopaminergic, glutamatergic, and serotonergic signaling pathways and thus improving schizophrenia-related symptoms[1]. Preclinical data indicate that DSR-141562 has a good therapeutic window, showing efficacy in various animal models of schizophrenia with no significant adverse reactions[2].
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| Molecular Formula |
C19H25F3N4O3
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|---|---|
| Molecular Weight |
414.4220
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| Exact Mass |
414.187
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| Elemental Analysis |
C, 55.07; H, 6.08; F, 13.75; N, 13.52; O, 11.58
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| CAS # |
2007975-22-4
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| PubChem CID |
122540493
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| Appearance |
White to off-white solid powder
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| LogP |
3.4
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
29
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| Complexity |
631
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
LNELWUPBSLZUIQ-MQMHXKEQSA-N
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| InChi Code |
InChI=1S/C19H25F3N4O3/c1-25-17(27)15-10-23-16(13-6-8-28-9-7-13)26(15)24-18(25)29-11-12-2-4-14(5-3-12)19(20,21)22/h10,12-14H,2-9,11H2,1H3/t12-,14-
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| Chemical Name |
3-Methyl-7-(tetrahydro-2H-pyran-4-yl)-2-[[trans-4-(trifluoromethyl)cyclohexyl]methoxy]imidazo[5,1-f][1,2,4]triazin-4(3H)-one
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| Synonyms |
DSR-141562; DSR-141562; DSR141562; DSR141562;; LMN75224; LMN-75224; LMN 75224;
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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 : ~25 mg/mL (~60.33 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.03 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 (6.03 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 (6.03 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 | 2.4130 mL | 12.0651 mL | 24.1301 mL | |
| 5 mM | 0.4826 mL | 2.4130 mL | 4.8260 mL | |
| 10 mM | 0.2413 mL | 1.2065 mL | 2.4130 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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