| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
PDE4D (phosphodiesterase 4D). D159687 is a selective PDE4D inhibitor with an IC50 of 27 nM against hPDE4D7. It has an IC50 ≥29 μM against PDE1, PDE2, PDE3, PDE5, PDE7, PDE8, PDE9, PDE10, and PDE11 subtypes, demonstrating high selectivity for PDE4D. By inhibiting PDE4D, it modulates cAMP signaling pathways in the central nervous system.
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| ln Vitro |
There is a brief rise in CREB phosphorylation caused by D159687 (1 μM, 0-24 hours), which peaks 6 hours after treatment [1]. A CREB phosphorylation of 1 μM is produced by D159687 (0.01-1 μM, 6 hours) [1].
D159687 induces a transient increase in CREB phosphorylation. At a concentration of 1 μM, it causes CREB phosphorylation that peaks at 6 hours after treatment. The compound produces optimal CREB phosphorylation at 1 μM, with a concentration range of 0.01-1 μM over 6 hours. CREB phosphorylation is a key event in synaptic plasticity and memory formation. |
| ln Vivo |
In female cynomolgus monkeys, D159687 (0.05–5 mg/kg; administered orally daily for one week) has been demonstrated to potentially recruit or enhance synapse function and raise task difficulty [2].
D159687 has been shown to potentially recruit or enhance synaptic function with increased task difficulty in female cynomolgus monkeys. At oral doses of 0.05-5 mg/kg administered daily for one week, it demonstrated procognitive effects. The compound also accelerated recovery from diazepam-induced ataxia but prolonged recovery from ethanol- and propofol-induced ataxia. It did not show antidepressant or anxiolytic benefit. |
| Enzyme Assay |
D159687 is evaluated in cell-free enzymatic assays using purified PDE4D enzyme. The compound is incubated with PDE4D and a substrate, and the inhibition of cAMP hydrolysis is measured. IC50 values are determined to quantify the potency of PDE4D inhibition. Selectivity is assessed by screening against a panel of phosphodiesterase subtypes, including PDE1, PDE2, PDE3, PDE5, PDE7, PDE8, PDE9, PDE10, and PDE11.
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: HT-22 (mouse hippocampal cell line) Tested Concentrations: 1 μM Incubation Duration: 0, 1, 3, 6, 12, 24 hrs (hours) Experimental Results: Induced a transient increase in CREB phosphorylation at 6 hrs (hours) Peak treatment is achieved several hrs (hours) after treatment. Western Blot Analysis[1] Cell Types: HT-22 (mouse hippocampal cell line) Tested Concentrations: 0.01 μM, 0.1 μM, 1 μM Incubation Duration: 6 hrs (hours) Experimental Results: CREB phosphorylation is optimal at 1 μM. D159687 is assessed in cell-based assays using HT-22 mouse hippocampal cell lines. Cells are treated with D159687 at concentrations ranging from 0.01 to 1 μM for up to 24 hours. Western blot analysis is performed to measure CREB phosphorylation. The compound induces a transient increase in CREB phosphorylation that peaks at 6 hours after treatment. Optimal CREB phosphorylation is observed at 1 μM. |
| Animal Protocol |
Animal/Disease Models: Female cynomolgus monkey (4-6 years old) [2]
Doses: 0.05, 0.5, 5 mg/kg Route of Administration: Orally daily for one week Experimental Results: Synaptic function may be recruited as task difficulty increases or enhance. D159687 is administered orally in female cynomolgus monkeys aged 4-6 years at doses of 0.05, 0.5, and 5 mg/kg daily for one week. The compound shows a potential recruitment or enhancement of synaptic function with increased task difficulty. It is a brain-penetrant compound, suggesting good central nervous system exposure. The compound is formulated for oral administration. |
| ADME/Pharmacokinetics |
D159687 is a brain-penetrant, orally available compound with good bioavailability. It is soluble in DMSO at 150 mg/mL (408.90 mM). The compound has a LogP of 5.683. It has a hydrogen bond donor count of 2, a hydrogen bond acceptor count of 2, and a rotatable bond count of 5. The compound should be stored at -20°C as a powder for up to 3 years. Stock solutions should be stored at -80°C for up to 6 months.
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| Toxicity/Toxicokinetics |
D159687 has reduced potential to cause emesis compared to other PDE4 inhibitors such as Rolipram. It is a negative allosteric modulator that does not completely inhibit enzymatic activity, which contributes to its improved safety profile. The compound is for research use only and is not intended for human therapeutic use. No detailed toxicity data beyond the reduced emetic potential is available.
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| References | |
| Additional Infomation |
D159687 is a brain-penetrant, orally available PDE4D negative allosteric modulator with a procognitive profile. It is more effective and much less emetic than Rolipram in vivo. The compound has a purity of ≥98% and is available as a white to off-white solid. It is also known by the synonyms D-159687 and D 159687. The compound has a CAS number of 1155877-97-6 and a PubChem CID of 57703712. It is used for research purposes only and has not been approved for clinical use.
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| Molecular Formula |
C21H19CLN2O2
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| Molecular Weight |
366.84
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| Exact Mass |
366.114
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| CAS # |
1155877-97-6
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| Related CAS # |
1155877-97-6
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| PubChem CID |
57703712
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| Appearance |
White to off-white solid powder
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| LogP |
5.683
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
26
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| Complexity |
453
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
RJJLUTWHJUDZFP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H19ClN2O2/c1-26-20-10-7-15(12-19(20)16-3-2-4-17(22)13-16)11-14-5-8-18(9-6-14)24-21(23)25/h2-10,12-13H,11H2,1H3,(H3,23,24,25)
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| Chemical Name |
[4-[[3-(3-Chlorophenyl)-4-methoxyphenyl]methyl]phenyl]urea
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| Synonyms |
D159687 D-159687 D 159687
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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 : ~150 mg/mL (~408.90 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.81 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 (6.81 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 (6.81 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 | 2.7260 mL | 13.6299 mL | 27.2598 mL | |
| 5 mM | 0.5452 mL | 2.7260 mL | 5.4520 mL | |
| 10 mM | 0.2726 mL | 1.3630 mL | 2.7260 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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