Kanwal Abhinav, Kanwar Navjot, Bharati Sanjay, Srivastava Prateek, Singh Shailendra P, Amar Salomon
Department of Pharmacology, All India Institute of Medical Sciences (AIIMS), Bathinda 151001, India.
University Institute of Pharmaceutical Sciences, UGC Centre for Advanced Studies, Panjab University, Chandigarh 160014, India.
Biomedicines. 2022 Jan 31;10(2):331. doi: 10.3390/biomedicines10020331.
There are substantial shortcomings in the drugs currently available for treatment of type 2 diabetes mellitus. The global diabetic crisis has not abated despite the introduction of new types of drugs and targets. Persistent unaddressed patient needs remain a significant factor in the quest for new leads in routine studies. Drug discovery methods in this area have followed developments in the market, contributing to a recent rise in the number of molecules. Nevertheless, troubling developments and fresh challenges are still evident. Recently, metformin, the most widely used first-line drug for diabetes, was found to contain a carcinogenic contaminant known as N-nitroso dimethylamine (NDMA). Therefore, purity and toxicity are also a big challenge for drug discovery and development. Moreover, newer drug classes against SGLT-2 illustrate both progress and difficulties. The same was true previously in the case of glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors. Furthermore, researchers must study the importance of mechanistic characteristics of novel compounds, as well as exposure-related hazardous aspects of current and newly identified protein targets, in order to identify new pharmacological molecules with improved selectivity and specificity.
目前可用于治疗2型糖尿病的药物存在重大缺陷。尽管引入了新型药物和靶点，但全球糖尿病危机仍未缓解。在常规研究中，持续未得到满足的患者需求仍是寻找新线索的一个重要因素。该领域的药物发现方法一直紧跟市场发展，导致最近分子数量有所增加。然而，令人担忧的发展情况和新挑战仍然明显。最近，糖尿病最广泛使用的一线药物二甲双胍被发现含有一种名为N-亚硝基二甲胺（NDMA）的致癌污染物。因此，纯度和毒性也是药物发现和开发面临的一大挑战。此外，针对SGLT-2的新型药物类别既显示出进展，也存在困难。以前胰高血糖素样肽-1受体激动剂和二肽基肽酶-4抑制剂的情况也是如此。此外，研究人员必须研究新型化合物的机制特征的重要性，以及当前和新发现的蛋白质靶点与暴露相关的危险方面，以便识别具有更高选择性和特异性的新药理分子。
