Abstract:
Protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs) regulate the level of tyrosine phosphorylation in proteins. PTKs are key enzymes that catalyze the transfer of an ATP phosphoric acid to a tyrosine residue on target protein substrates. Protein tyrosine phosphatases (PTPs) are responsible for the dephosphorylation of tyrosine residues and play a role in countering PTK overactivity. As widespread oncogenes, PTKs were once considered to be promising targets for therapy. However, tyrosine kinase inhibitors (TKIs) now face a number of challenges, including drug resistance and toxic side effects. Treatment strategies now need to be developed from a new perspective. In this review, we assess the current state of TKIs and highlight the role of PTPs in cancer and other diseases. With the advances of allosteric inhibition and the development of multiple alternative proprietary drug strategies, the reputation of PTPs as \"undruggable\" targets has been overturned, and they are now considered viable therapeutic targets. We also discuss the strategies and prospects of PTP-targeted therapy, as well as its future development.
摘要:
蛋白质酪氨酸激酶(PTKs)和蛋白质酪氨酸磷酸酶(PTP)调节蛋白质中酪氨酸磷酸化的水平。PTKs是催化ATP磷酸转移至靶蛋白底物上的酪氨酸残基的关键酶。蛋白酪氨酸磷酸酶(PTP)负责酪氨酸残基的去磷酸化,并在抵抗PTK过度活性中起作用。作为广泛存在的癌基因,PTK曾经被认为是有希望的治疗靶标。然而,酪氨酸激酶抑制剂(TKIs)现在面临着许多挑战,包括耐药性和毒副作用。现在需要从新的角度制定治疗策略。在这次审查中,我们评估了TKIs的现状,并强调了PTP在癌症和其他疾病中的作用.随着变构抑制技术的进步和多种替代专利药物策略的发展,PTP作为“不可吸毒”目标的声誉已被推翻,它们现在被认为是可行的治疗目标。我们还讨论了PTP靶向治疗的策略和前景,以及它的未来发展。