LEO 39652
Based on 1 Customer Validation
LEO 39652 is a dual-soft PDE4 inhibitor with IC50s of 1.2 nM, 1.2 nM, 3.0 nM and 3.8 nM for PDE4A, PDE4B, PDE4C and PDE4D, respectively. LEO 39652 also inhibits TNF-α with an IC50 value of 6.0 nM. LEO 39652 is used for topical research of Atopic dermatitis (AD) .
연구목적의 판매만을 진행합니다. 환자를 대상으로 한 판매는 하지 않습니다.
- Purity : 99.40%
- CAS No.: 1445656-91-6
- 화학식: C23H23N3O5
- 분자량:421.45
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보관:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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용액&용해도
- Protocol
- 순도&문서
- References
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Help & FAQs
Biological Activity
제품 설명
IC50 & Target
[1]|
PDE4D 3.8 nM (IC50) |
TNF-α 6.0 nM (IC50) |
PDE4A 1.2 nM (IC50) |
PDE4B 1.2 nM (IC50) |
PDE4C2 3.0 nM (IC50) |
In Vitro
LEO 39652 shows unbound in vitro potency when measured as LPS induced TNF-α release in human peripheral blood mononuclear cells (PBMC), incubated in serum free medium. LEO 39652 shows a relatively high binding to human serum albumin[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
In Vivo
LEO 39652 exhibits total clearance (rats 930, minipigs 200 and monkey 300 mL/min/kg) and ratio to total AUC (rats 4, minipigs 6 and monkey 6 %) following intravenous administration (rats 0.075, minipigs 0.5 and monkeys 2.0 mg/kg)[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:3 male Sprague Dawley rats, 2 female Göttingen minipigs, 2 male Göttingen minipigs, 2 female cynomolgus monkeys and 2 male cynomolgus monkeys[1]
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Dosage:Rats 0.075, minipigs 0.5 and monkeys 2.0 mg/kg
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Administration:Intravenous injection
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Result:Total clearance of 930, 200 and 300 mL/min/kg for rats, minipigs and monkeys, respectively.
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 1445656-91-6
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Appearance Solid
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분자량 421.45
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화학식 C23H23N3O5
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Color Off-white to gray
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SMILES
O=C(C1(C2=NN3C(C4=CC5=C(C(OC5)=O)C=C4)=CC=C(OC)C3=N2)CC1)OCC(C)C
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
용액&용해도
In Vitro:
DMSO : 25 mg/mL (59.32 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Protocol
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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TPA/Croton Oil Ear Edema and Dermatitis
The TPA (12-O-tetradecanoylphorbol-13-acetate) and croton oil-induced mouse ear edema model is a well-established acute cutaneous inflammation system used to evaluate topical anti-inflammatory activity by measuring edema formation, neutrophil infiltration, vascular permeability, and cytokine-mediated skin responses in vivo. The inflammatory response is triggered by topical application of phorbol esters (TPA) or croton oil constituents, leading to rapid activation of protein kinase C signaling, leukocyte recruitment, and increased vascular permeability, which can be quantified by ear thickness, weight, dye extravasation, and biochemical markers such as myeloperoxidase (MPO) activity and pro-inflammatory mediators in ear tissue homogenates. This model is widely used for screening anti-inflammatory agents, where reductions in edema and inflammatory biomarkers reflect suppression of acute dermal inflammation and immune cell infiltration. Histological evaluation typically confirms epidermal
순도&문서
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Data Sheet (281 KB)
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SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Korean - KR (251 KB)
- Portuguese - PT (251 KB)
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Handling Instructions (2659 KB)
References
[1]. Jens Larsen, et al. Discovery and Early Clinical Development of Isobutyl 1-[8-Methoxy-5-(1-oxo-3 H-isobenzofuran-5-yl)-[1,2,4]triazolo[1,5- a]pyridin-2-yl]cyclopropanecarboxylate (LEO 39652), a Novel "Dual-Soft" PDE4 Inhibitor for Topical Treatment of Ato [Content Brief]
[2]. Stefan Eirefelt, et al. Evaluating Dermal Pharmacokinetics and Pharmacodymanic Effect of Soft Topical PDE4 Inhibitors: Open Flow Microperfusion and Skin Biopsies. Pharm Res. 2020 Nov 13;37(12):243. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.3728 mL | 11.8638 mL | 23.7276 mL | 59.3190 mL |
| 5 mM | 0.4746 mL | 2.3728 mL | 4.7455 mL | 11.8638 mL | |
| 10 mM | 0.2373 mL | 1.1864 mL | 2.3728 mL | 5.9319 mL | |
| 15 mM | 0.1582 mL | 0.7909 mL | 1.5818 mL | 3.9546 mL | |
| 20 mM | 0.1186 mL | 0.5932 mL | 1.1864 mL | 2.9660 mL | |
| 25 mM | 0.0949 mL | 0.4746 mL | 0.9491 mL | 2.3728 mL | |
| 30 mM | 0.0791 mL | 0.3955 mL | 0.7909 mL | 1.9773 mL | |
| 40 mM | 0.0593 mL | 0.2966 mL | 0.5932 mL | 1.4830 mL | |
| 50 mM | 0.0475 mL | 0.2373 mL | 0.4746 mL | 1.1864 mL |
LEO 39652 Related Classifications
HY-131707 Related Classifications
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