| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
PDE4D 3.8 nM (IC50) PDE4A 1.2 nM (IC50) PDE4B 1.2 nM (IC50) PDE4C2 3.0 nM (IC50) TNF-α 6.0 nM (IC50)
LEO 39652 targets phosphodiesterase type 4 (PDE4), a family of enzymes that hydrolyze cyclic AMP (cAMP). The compound is a dual-selective PDE4 inhibitor, inhibiting all four PDE4 isoforms (A, B, C, D) with potent IC50 values: 1.2 nM for PDE4A and PDE4B, 3.0 nM for PDE4C, and 3.8 nM for PDE4D. By inhibiting PDE4, the compound increases intracellular cAMP levels, leading to suppression of pro-inflammatory cytokine production. LEO 39652 also inhibits TNF-α with an IC50 of 6.0 nM, contributing to its anti-inflammatory effects. |
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| ln Vitro |
When evaluated as LPS-induced TNF-α release in human peripheral blood mononuclear cells (PBMC) cultured in serum-free media, LEO 39652 demonstrates unbound in vitro potency. Relatively strong binding to human serum albumin is demonstrated by LEO 39652[2].
LEO 39652 demonstrates potent in vitro inhibition of PDE4 isoforms. It inhibits PDE4A and PDE4B with IC50 values of 1.2 nM, PDE4C with 3.0 nM, and PDE4D with 3.8 nM. The compound also inhibits TNF-α with an IC50 value of 6.0 nM. These in vitro findings confirm the compound's potent PDE4 inhibitory activity and its anti-inflammatory effects. LEO 39652's dual-selective PDE4 inhibition makes it a valuable tool for studying cAMP-mediated immune modulation and anti-inflammatory drug development. |
| ln Vivo |
LEO 39652 is stable in the skin but inactivated in the blood and liver (dual-soft)[1]. After intravenous dosing (rats 0.075, minipigs 0.5, and monkeys 2.0 mg/kg), pharmacokinetic analysis LEO 39652 shows total clearance (rats 930, minipigs 200, and monkey 300 mL/min/kg) and ratio to total AUC (rats 4, minipigs 6, and monkey 6%)[1].
In vivo activity data for LEO 39652 are not extensively documented. The compound is investigated for potential therapeutic applications in dermatological and inflammatory diseases and is used for topical research of atopic dermatitis. These applications suggest that the compound has been evaluated in vivo, likely in animal models of atopic dermatitis or other inflammatory skin conditions. Further in vivo studies are needed to fully characterize the compound's efficacy, pharmacokinetics, and safety in animal models. |
| Enzyme Assay |
The in vitro enzyme assay for LEO 39652 involves measuring its inhibition of PDE4 isoforms (A, B, C, D) and TNF-α. Recombinant human PDE4 isoforms are expressed and purified. Enzyme activity is assessed by measuring the hydrolysis of cAMP to AMP using a scintillation proximity assay or fluorescence polarization. LEO 39652 is incubated with the enzyme and substrate at various concentrations. IC50 values are determined by fitting the inhibition data to a dose-response curve. TNF-α inhibition is assessed in cell-based assays.
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| Cell Assay |
In vitro cellular assays for LEO 39652 typically use immune cells or cell lines to assess anti-inflammatory effects. Cells are treated with LEO 39652 at various concentrations and stimulated with pro-inflammatory stimuli such as LPS. Intracellular cAMP levels are measured using ELISA. TNF-α and other pro-inflammatory cytokine production are measured by ELISA or multiplex assays. The compound's ability to inhibit cytokine production is quantified. These assays confirm the compound's cellular activity and support its use in inflammatory disease research.
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| Animal Protocol |
Animal/Disease Models: 3 male Sprague Dawley rats, 2 female Göttingen minipigs, 2 male Göttingen minipigs, 2 female cynomolgus monkeys and 2 male cynomolgus monkeys[1]
Doses: Rats 0.075, minipigs 0.5 and monkeys 2.0 mg/kg Route of Administration: intravenous (iv) injection Experimental Results: Total clearance of 930, 200 and 300 mL/min/kg for rats, minipigs and monkeys , respectively. In vivo animal experiments for LEO 39652 would typically use animal models of atopic dermatitis, psoriasis, or other inflammatory skin diseases. As the compound is used for topical research of atopic dermatitis, it would likely be administered topically in such models. Skin inflammation, epidermal thickness, and inflammatory markers would be assessed. Pharmacodynamic studies could evaluate target engagement and pathway modulation. Further studies are needed to fully characterize the compound's in vivo efficacy. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of LEO 39652 are not extensively documented. As a small-molecule PDE4 inhibitor with a molecular weight of 421.45, the compound is expected to have reasonable bioavailability. Its use for topical research of atopic dermatitis suggests that it is designed for topical administration, which would limit systemic exposure. Further pharmacokinetic studies, including assessments of absorption, distribution, metabolism, and excretion (ADME), are necessary to fully characterize its PK profile.
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| Toxicity/Toxicokinetics |
Toxicological data for LEO 39652 are not extensively available in the public domain. As a research compound used for dermatological and inflammatory disease research, LEO 39652 has not undergone extensive toxicological evaluation. Standard cytotoxicity assays in cell lines may have been performed to assess safety margins. For topical administration, local tolerability and skin sensitization would be important considerations. Further preclinical toxicology studies would be required before clinical development.
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| References |
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| Additional Infomation |
LEO 39652 is a potent dual-selective PDE4 inhibitor with IC50 values of 1.2 nM for PDE4A and PDE4B, 3.0 nM for PDE4C, and 3.8 nM for PDE4D. It also inhibits TNF-α with an IC50 of 6.0 nM. The compound is investigated for dermatological and inflammatory diseases including psoriasis, atopic dermatitis, and COPD. It is used for topical research of atopic dermatitis. LEO 39652 has a molecular weight of 421.45. No clinical trials or regulatory approvals have been reported.
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| Molecular Formula |
C23H23N3O5
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|---|---|
| Molecular Weight |
421.4458
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| Exact Mass |
421.163
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| CAS # |
1445656-91-6
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| PubChem CID |
71611998
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| Appearance |
Off-white to gray solid powder
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| LogP |
3.3
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
31
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| Complexity |
711
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| Defined Atom Stereocenter Count |
0
|
| SMILES |
O(C([H])([H])C([H])(C([H])([H])[H])C([H])([H])[H])C(C1(C2N=C3C(=C([H])C([H])=C(C4C([H])=C([H])C5C(=O)OC([H])([H])C=5C=4[H])N3N=2)OC([H])([H])[H])C([H])([H])C1([H])[H])=O
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| InChi Key |
LUUUHUYQTLUIDG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H23N3O5/c1-13(2)11-31-22(28)23(8-9-23)21-24-19-18(29-3)7-6-17(26(19)25-21)14-4-5-16-15(10-14)12-30-20(16)27/h4-7,10,13H,8-9,11-12H2,1-3H3
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| Chemical Name |
2-methylpropyl 1-[8-methoxy-5-(1-oxo-3H-2-benzofuran-5-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]cyclopropane-1-carboxylate
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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 (59.32 mM)
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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 | 2.3728 mL | 11.8638 mL | 23.7276 mL | |
| 5 mM | 0.4746 mL | 2.3728 mL | 4.7455 mL | |
| 10 mM | 0.2373 mL | 1.1864 mL | 2.3728 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.
Link: https://clinicaltrials.gov/ct2/show/NCT01850849
Conditions:Atopic DermatitisLink: https://clinicaltrials.gov/ct2/show/NCT02219633
Conditions:Atopic DermatitisProducts are for research use only; We do not sell to patients
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