Integrated Drug Discovery Centre, Department of Pharmaceutical Chemistry, Acharya & BM Reddy College of Pharmacy, Bengaluru 560107, Karnataka, India.
Integrated Drug Discovery Centre, Department of Pharmaceutical Chemistry, Acharya & BM Reddy College of Pharmacy, Bengaluru 560107, Karnataka, India.
Bioorg Chem. 2023 Jan;130:106215. doi: 10.1016/j.bioorg.2022.106215. Epub 2022 Oct 21.
Discoidin domain receptors (DDRs) are one of the less explored targets for the treatment of cancer which belong to receptor tyrosine kinases family. Discoidin domain receptors (DDRs) are a collagen-activated receptor tyrosine kinase and essential for controlling cellular functions like proliferation, morphogenesis, adhesion, differentiation, invasion, matrix remodeling, and migration. Although there are many targets and their inhibitors are reported which treat cancer. But most of drugs were amalgamated with moderate to severe side effects. This results in untreated cancerous cells. One of the reasons that cancer is considered challenging to treat because the targets were mutating rapidly and the inhibitor become less potent. The target identification is a tedious task for the researchers from the early 1990 s till date. When it comes to cancer, there has not been any magical stick to treat it undisputedly. Therefore, need for discovery of new receptor may helpful to overcome these difficulties. The development of DDR inhibitors has received a lot of attention ever since the target was discovered. In this review we have reported the development of most promising DDR1 and DDR2 small molecule inhibitors from the perspective of medicinal chemistry. We have also discussed about the clinical trials, recent patents, selectivity biological activity, and structure-activity relationship (SAR) of DDR1 and DDR2 inhibitors.
Discoidin domain receptors (DDRs) 是癌症治疗中研究较少的靶点之一，属于受体酪氨酸激酶家族。Discoidin domain receptors (DDRs) 是一种胶原激活的受体酪氨酸激酶，对于控制细胞功能如增殖、形态发生、黏附、分化、侵袭、基质重塑和迁移至关重要。虽然有许多被报道的靶点及其抑制剂可以治疗癌症，但大多数药物都伴有中度至重度的副作用。这导致未治疗的癌细胞存活。癌症被认为难以治疗的原因之一是靶点迅速突变，抑制剂的效力降低。自 20 世纪 90 年代初以来，靶标识别一直是研究人员的一项艰巨任务。说到癌症，目前还没有任何神奇的方法可以无可争议地治疗它。因此，需要发现新的受体来克服这些困难。自从发现该靶点以来，DDR 抑制剂的开发一直受到广泛关注。在这篇综述中，我们从药物化学的角度报告了最有前途的 DDR1 和 DDR2 小分子抑制剂的开发。我们还讨论了 DDR1 和 DDR2 抑制剂的临床试验、最新专利、选择性生物活性和构效关系 (SAR)。
