Orismilast
(Synonyms: LEO-32731) 目录号 : GC64773
Orismilast (LEO-32731) 是一种PDE4抑制剂，用于炎症性疾病的研究。
Cas No.:1353546-86-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Orismilast (LEO-32731) is a PDE4 inhibitor used for the research of inflammatory diseases[1].
[1]. Nielsen,et al.Preparation of benzodioxole or benzodioxepine heterocyclic compounds as phosphodiesterase inhibitors.WO2011160632A1.
| Cas No. | 1353546-86-7 | SDF | Download SDF |
| 别名 | LEO-32731 | ||
| 分子式 | C19H15Cl2F2NO7S | 分子量 | 510.29 |
| 溶解度 | DMSO : 100 mg/mL (195.97 mM; Need ultrasonic) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.9597 mL | 9.7983 mL | 19.5967 mL |
| 5 mM | 0.3919 mL | 1.9597 mL | 3.9193 mL |
| 10 mM | 0.196 mL | 0.9798 mL | 1.9597 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Pharmacology of Orismilast, a potent and selective PDE4 inhibitor
J Eur Acad Dermatol Venereol 2023 Apr;37(4):721-729.PMID:36527389DOI:10.1111/jdv.18818.
Background: There remains an unmet need for oral medications that are safe and efficacious for long-term management of chronic inflammatory skin diseases (CISD). Inhibition of phosphodiesterase 4 (PDE4) can modulate a broad range of pro-inflammatory cytokines that play a major role in CISD pathogenesis. Orismilast is a second generation PDE4 inhibitor in clinical development for CISD treatment. Objectives: The objective of this study was to examine the PDE4 enzymatic activity and anti-inflammatory effects of Orismilast in vitro, ex vivo, and in vivo. Methods: The PDE1-11 enzymatic activity of Orismilast was tested in vitro using a single concentration of 308 nM Orismilast. The PDE4 selectivity and inhibitory potency was further examined in a radiometric assay. Orismilast was tested on human whole blood and human peripheral blood mononuclear cells (PBMC) to determine effects on its cytokine secretion and inhibition profile ex vivo. Orismilast was orally administered in a murine model of chronic oxazolone-induced ear skin inflammation. Ear thickness, a marker of inflammation, and inflammatory cytokines were analysed. Results: Orismilast selectively inhibited PDE4 and demonstrated potent inhibition of PDE4B and PDE4D subtype splice variants in vitro. Orismilast inhibited whole blood and PBMC production of tumour necrosis factor α (TNFα), and the secretion of T-helper (Th)1 (TNFα and IFNγ), Th17 (IL-22 and IL-23), and Th2 (IL-4, IL-5, and IL-13) related cytokines in PBMC. In vivo, 10 and 30 mg/kg doses of Orismilast significantly reduced ear thickness and inflammation markers (p < 0.0001, respectively). Conclusion: Orismilast displayed selective and potent PDE4 inhibition and broad-spectrum anti-inflammatory activity in several pre-clinical models. The results of the study support clinical development of oral Orismilast as a novel treatment option for CISD including psoriasis, atopic dermatitis, and hidradenitis suppurativa.
Oral Orismilast: Efficacy and safety in moderate-to-severe psoriasis and development of modified release tablets
J Eur Acad Dermatol Venereol 2023 Apr;37(4):711-720.PMID:36478476DOI:10.1111/jdv.18812.
Background: Orismilast is a high-potency phosphodiesterase 4 (PDE4) inhibitor with enhanced selectivity for the PDE4B and PDE4D subtypes. Objectives: The objective of this phase 2a trial was to examine the efficacy and safety of Orismilast for psoriasis using a first-generation immediate-release (IR) formulation. The objective of the subsequent phase 1 trial was to test new formulations designed to minimize the gastrointestinal (GI)-related adverse events (AEs) observed with the first-generation IR formulation. We examined the following: (1) pharmacokinetic (PK) properties of Orismilast modified release (MR) and IR, (2) food effects on PK properties of Orismilast MR or IR, (3) safety of Orismilast MR compared to placebo. Methods: In a phase 2a prospective, randomized, double-blind, placebo-controlled trial, patients with moderate-to-severe psoriasis were randomized to receive 30 mg oral Orismilast IR or placebo over 16 weeks. The single-site phase 1 trial consisted of three parts: (1) participants received a single 30 mg dose of Orismilast MR and IR (open-label), (2) participants received 30 mg Orismilast MR or IR under either fasting condition, following a high-fat meal or low-fat meal (open-label) and (3) participants received up to 60 mg Orismilast MR twice-daily or a placebo for 17 days (double-blind). Results: In the phase 2a trial, treatment with Orismilast IR significantly improved the mean Psoriasis Area Severity Index score at week 16 compared to placebo. The phase 1 trial revealed comparable PK properties of the Orismilast MR and IR formulations, with participants in the Orismilast MR group experiencing fewer GI-related AEs than those receiving Orismilast IR (16.7% vs. 33.3%). Conclusion: Orismilast IR displayed higher efficacy compared to placebo in patients with moderate-to-severe psoriasis at week 16. Orismilast MR had similar PK properties and fewer GI disorders compared to the IR formulation in healthy participants. Future development of Orismilast will be based on the MR formulation.