COX-2/5-LOX inhibitors(University of Alberta)(COX-2/5-LOX inhibitors(University of Alberta)) - 药物靶点：5-LOX x COX-2_在研适应症：炎症_专利_临床

概要

基本信息

药物类型

小分子化药

别名-

靶点

5-LOX x COX-2

作用方式

抑制剂

作用机制

5-LOX抑制剂(5-脂氧合酶抑制剂)、COX-2抑制剂(环氧化酶-2抑制剂)

治疗领域

其他疾病

在研适应症

炎症

非在研适应症-

原研机构

University of Alberta

在研机构

University of Alberta

非在研机构-

权益机构-

最高研发阶段临床前

首次获批日期-

最高研发阶段(中国)-

特殊审评-

结构/序列

分子式C16H11F5N4O3S

InChIKeyFIZIEQVDEPGNOZ-UHFFFAOYSA-N

CAS号1131479-24-7

关联

100 项与 COX-2/5-LOX inhibitors(University of Alberta) 相关的临床结果

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100 项与 COX-2/5-LOX inhibitors(University of Alberta) 相关的转化医学

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100 项与 COX-2/5-LOX inhibitors(University of Alberta) 相关的专利（医药）

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44

项与 COX-2/5-LOX inhibitors(University of Alberta) 相关的文献（医药）

2026-04-08·Anti-Cancer Agents in Medicinal Chemistry

Targeting the Arachidonic Acid Cascade in Cancer: Recent Advances in Enzyme Inhibitor Design

Article

作者: Savić, Jelena ; Čudina, Olivera ; Brborić, Jasmina ; Dobričić, Vladimir ; Vujić, Zorica

Introduction::

Cancer is a multifactorial disease involving multiple interrelated molecular targets and signaling pathways. Some epidemiological studies have suggested that nonsteroidal anti-inflammatory drugs could reduce the incidence of certain types of cancer, indicating the interplay between inflammation and cancer. Designing compounds that inhibit an enzyme of the arachidonic acid inflammatory cascade while exhibiting anticancer effects has emerged as a promising strategy.

Methods::

A descriptive review and analysis of recently published studies on the synthesis of compounds that target two enzymes of the arachidonic acid cascade and simultaneously exhibit anticancer activity was performed.

Results::

Numerous cyclooxygenase-2 (COX-2) inhibitors with anticancer activity are known. Fewer examples exist for 5-lipoxygenase (5-LOX) inhibitors, while many dual COX-2/5-LOX inhibitors also display anticancer effects. Some examples of dual inhibitors with anticancer potential include 5-LOX/microsomal prostaglandin E2 synthase (mPGES), and COX-2/soluble epoxide hydrolase inhibitors. There are also compounds designed to inhibit three targets: COX-2, 15-LOX, and carbonic anhydrase.

Discussion::

Given the complex interplay between inflammation and cancer, the term "anticancer effects" encompasses various therapeutic opportunities, ranging from adjuvant therapy and chemoprevention to angiogenic and cytotoxic activity.

Conclusion::

This multitarget approach highlights the broad therapeutic possibilities of targeting inflammatory pathways, establishing a direction for the development of innovative anticancer therapies with improved safety profiles.

2026-01-22·JOURNAL OF MEDICINAL CHEMISTRY

Design, Synthesis, and Evaluation of Organic and Organometallic Pyrazoline Derivatives as Selective Dual COX-2/5-LOX Inhibitors and Potential Anticancer Agents

Article

作者: Flores, Erick ; Morales, Pilar ; Navarrete, Elizabeth ; Cariou, Kevin ; Blacque, Olivier ; Muñoz-Osses, Michelle ; Mascayano, Carolina ; Mesdom, Pierre ; Cáceres M, Tomás ; Godoy, Fernando ; Gasser, Gilles

Inspired by the structure of the anti-inflammatory drug Celecoxib, which is currently used in cancer prevention and treatment, we report the design, synthesis, and biological evaluation of organic and organometallic molecular hybrids based on pyrazolines (4a-h). Structure-Activity Relationship (SAR) analyses showed that the combination of catechol-benzenesulfonamide in 4a (organic) and 4c (ferrocenyl) derivatives acts as potent and highly selective dual inhibitors (IC₅₀ COX-2 = 4.58 and 2.88 μM; IC₅₀ 5-LOX = 0.23 and 0.10 μM, respectively; evaluated against COX-1 and 15-LOX isoforms). Molecular dynamics simulations of 4a and 4c in 5-LOX showed their preferential localization at the allosteric site and at the entry channel, respectively, consistent with their noncompetitive (4a) and mixed (4c) kinetics. Furthermore, the noncytotoxic complex 4c (MRC-5, CC₅₀ = 38.13 μM) exhibited anticancer effects in ovarian cancer cells (A2780, CC₅₀ = 13.79 μM) that overexpress the proinflammatory enzymes COX-2 and 5-LOX (Western Blot), exceeding the activity of the drug Celecoxib.

2026-01-17·Future Medicinal Chemistry

Bridging the gap with amide linkers: rational design, synthesis, and multi-target evaluation of sulfonamide/acetamide-NSAID hybrids as dual COX-2/5-LOX inhibitors

Article

作者: Fayed, Eman A. ; Ragab, Ahmed ; Al-Sanea, Mohammad M. ; Ali, Omaima ; Elzaitony, Asmaa S. ; Ramsis, Triveena M. ; Abusaif, Moustafa S. ; Musa, Arafa ; Ammar, Yousry A. ; Hussein, Shaimaa ; Kamal, Mona M.

AIM:

Novel hybrids of ibuprofen and naproxen were designed as dual COX-2/5-LOX inhibitors to create safer anti-inflammatory drugs.

MATERIALS AND METHODS:

The prodrugs were developed through a hybridization molecular approach; their potency against COX-1, COX-2, and 5-LOX was assessed, alongside measurements of PGE2 levels, NO scavenging, and mTOR and Nrf2 protein expression. Molecular docking was used to predict binding interactions.

RESULTS:

Hybrids 9 and 10 showed excellent COX-2 inhibition with IC₅₀ values of 3.3 and 2.0 µM, respectively, and high selectivity indices (SI) of 20.7 and 17.2. Both hybrids also demonstrated substantial 5-LOX inhibition with IC₅₀ values of 3.1 and 4.2 µM.

CONCLUSION:

The new hybrids exhibit strong COX-2/5-LOX inhibition, suggesting their structural framework is crucial for developing safer anti-inflammatory drugs.

100 项与 COX-2/5-LOX inhibitors(University of Alberta) 相关的药物交易

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