Background: Inflammatory diseases are one of the major concerns of today’s world; major disorders caused by inflammation include, allergy, asthma, arthritis, hepatitis, autoimmune diseases, celiac disease, etc. During most of these events, many proteins and molecules expression are modulated and one such protein is AP-1 (c-Fos-c-Jun heterodimer complex). AP-1 is a dimeric protein activated by several physiological stimuli and environmental insults such as growth factors, polypeptide hormones, neurotransmitters, cytokines, cell-matrix interactions, UV irradiations, viral and bacterial infections.

Objective: Present study is mainly focused on designing small molecule analogs to inhibit the c- Fos-c-Jun complex, as the complex is involved in many inflammatory diseases and precisely involved in disease progression. Therefore, it had been considered as a therapeutic target for more than a decade.

Materials and Methods: In the present study, an attempt was made to design the analogs of referral drug T-5224. 31 analogs of T-5224 were designed by chemoinformatics approach and subjected to ADMETox for screening.

Results: Among the 16 compounds that were found to pass the evaluation, all 16 compounds passed the toxicity evaluation except the 7th molecule. The molecular docking study showed that compounds 1, 2 and 16 had high inhibition constant.

Conclusion: The preliminary results suggest the compounds 1, 2 and 16 have the potential ligand binding capacity with the cFos-cJun complex. Further analysis, with advanced tools, may result in potential small molecules to inhibit the c-Fos-c-Jun complex.

背景：炎症性疾病是当今世界的主要问题之一。炎症引起的主要疾病包括过敏、哮喘、关节炎、肝炎、自身免疫性疾病、乳糜泻等。在大多数这些事件中，许多蛋白质和分子表达受到调节，其中一种蛋白质是 AP-1 (c-Fos-c -Jun 异二聚体复合物）。AP-1 是一种二聚体蛋白，可被多种生理刺激和环境损伤激活，例如生长因子、多肽激素、神经递质、细胞因子、细胞基质相互作用、紫外线照射、病毒和细菌感染。

目的：目前的研究主要集中在设计小分子类似物来抑制 c-Fos-c-Jun 复合物，因为该复合物涉及许多炎症性疾病，并精确参与疾病进展。因此，十多年来，它一直被认为是一种治疗靶点。

材料和方法：在本研究中，尝试设计转诊药物 T-5224 的类似物。通过化学信息学方法设计了 31 个 T-5224 类似物，并进行 ADMETox 筛选。

结果：在通过评价的16种化合物中，除第7分子外，其余16种化合物均通过了毒性评价。分子对接研究表明，化合物1、2、16具有较高的抑制常数。

结论：初步结果表明化合物 1、2 和 16 具有与 cFos-cJun 复合物的潜在配体结合能力。使用先进的工具进一步分析可能会产生潜在的小分子来抑制 c-Fos-c-Jun 复合物。