Background: The inflammatory process is one of the mechanisms by which our body upholds us from pathogens such as parasites, bacteria, viruses, and other harmful microorganisms. Inflammatory stimuli activate many intracellular signaling pathways such as the nuclear factor-kB (NF-kB) pathway and three mitogen-activated protein kinase (MAPK) pathways, which are mediated through extracellular-signal regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38. The p38 has evolved as an enticing target in treating many persistent inflammatory diseases. Hence, designing novel p38 inhibitors targeting MAPK pathways has acquired significance.

Objective: Peruse to identify the lead target to discover novel p38MAPK inhibitors with different scaffolds having improved selectivity over the prototype drugs.

Methods: Structure and the binding sites of p38MAPK were focused. Various scaffolds designed for inhibition and the molecules which have entered the clinical trials are discussed.

Results: This review aspires to present the available information on the structure and the 3D binding sites of p38MAPK, various scaffolds designed for imidazole, urea, benzamide, azoles, quinoxaline, chromone, ketone as a potent p38MAPK inhibitors and their SAR studies and the molecules which have entered the clinical trials.

Conclusion: The development of successful selective p38MAPK inhibitors in inflammatory diseases is in progress despite all challenges. It was speculated that p38MAPK also plays an important role in treating diseases such as neuroinflammation, arterial inflammation, vascular inflammation, cancer and so on, which are posing the world with treatment challenges. In this review, clinical trials of drugs are discussed related to inflammatory and its related diseases. Research is in progress to design and develop novel p38MAPK inhibitors with minimal side effects.

背景：炎症过程是我们的身体保护我们免受寄生虫、细菌、病毒和其他有害微生物等病原体侵害的机制之一。炎症刺激激活许多细胞内信号通路，如核因子-kB (NF-kB) 通路和三种丝裂原活化蛋白激酶 (MAPK) 通路，这些通路通过细胞外信号调节激酶 (ERK)、c-Jun N-末端激酶 (JNK) 和 p38。p38 已发展成为治疗许多持续炎症性疾病的诱人目标。因此，设计靶向 MAPK 通路的新型 p38 抑制剂具有重要意义。

目的：仔细确定主要靶点，以发现具有不同支架的新型 p38MAPK 抑制剂，其选择性优于原型药物。

方法：重点研究p38MAPK的结构和结合位点。讨论了设计用于抑制的各种支架和已进入临床试验的分子。

结果：本综述旨在提供有关 p38MAPK 的结构和 3D 结合位点的可用信息，为咪唑、尿素、苯甲酰胺、唑类、喹喔啉、色酮、酮设计的各种支架作为有效的 p38MAPK 抑制剂及其 SAR 研究和分子已进入临床试验。

结论：尽管存在所有挑战，但在炎症性疾病中成功的选择性 p38MAPK 抑制剂的开发仍在进行中。据推测，p38MAPK在神经炎症、动脉炎症、血管炎症、癌症等疾病的治疗中也发挥着重要作用，这些疾病给世界带来了治疗挑战。在这篇综述中，讨论了与炎症及其相关疾病相关的药物临床试验。正在研究设计和开发具有最小副作用的新型 p38MAPK 抑制剂。