Department of Pathology, Faculty of Medicine, Wroclaw Medical University, Wroclaw, Poland (S.M., M.W., S.A.); Department and Clinic of Internal Medicine, Occupational Diseases, Hypertension and Clinical Oncology, Wroclaw Medical University, Wroclaw, Poland (S.A.); and Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Faculty of Chemistry (M.K., G.P.-G., W.S.) and Biotechnology Centre (M.K., G.P.-G., W.S.), Silesian University of Technology, Gliwice, Poland.
Department of Pathology, Faculty of Medicine, Wroclaw Medical University, Wroclaw, Poland (S.M., M.W., S.A.); Department and Clinic of Internal Medicine, Occupational Diseases, Hypertension and Clinical Oncology, Wroclaw Medical University, Wroclaw, Poland (S.A.); and Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Faculty of Chemistry (M.K., G.P.-G., W.S.) and Biotechnology Centre (M.K., G.P.-G., W.S.), Silesian University of Technology, Gliwice, Poland
J Pharmacol Exp Ther. 2020 May;373(2):204-212. doi: 10.1124/jpet.119.263657. Epub 2020 Mar 10.
Despite the progress in the development of novel treatment modalities, a significant portion of patients with psoriasis remains undertreated relative to the severity of their disease. Recent evidence points to targeting the glucose transporter 1 and sugar metabolism as a novel therapeutic strategy for the treatment of psoriasis and other hyperproliferative skin diseases. In this review, we discuss glycoconjugation, an approach that facilitates the pharmacokinetics of cytotoxic molecules and ensures their preferential influx through glucose transporters. We propose pathways of glycoconjugate synthesis to increase effectiveness, cellular selectivity, and tolerability of widely used antipsoriatic drugs. The presented approach exploiting the heightened glucose requirement of proliferating keratinocytes bears the potential to revolutionize the management of psoriasis. SIGNIFICANCE STATEMENT: Recent findings concerning the fundamental role of enhanced glucose metabolism and glucose transporter 1 overexpression in the pathogenesis of psoriasis brought to light approaches that proved successful in cancer treatment. Substantial advances in the emerging field of glycoconjugation highlight the rationale for the development of glucose-conjugated antipsoriatic drugs to increase their effectiveness, cellular selectivity, and tolerability. The presented approach offers a novel therapeutic strategy for the treatment of psoriasis and other hyperproliferative skin diseases.
尽管在开发新型治疗方法方面取得了进展，但相对于疾病的严重程度，仍有相当一部分银屑病患者治疗不足。最近的证据表明，针对葡萄糖转运蛋白 1 和糖代谢是治疗银屑病和其他过度增殖性皮肤病的一种新的治疗策略。在这篇综述中，我们讨论了糖基化，这是一种促进细胞毒性分子药代动力学的方法，并确保它们通过葡萄糖转运体优先流入。我们提出了糖缀合物合成的途径，以提高广泛使用的抗银屑病药物的有效性、细胞选择性和耐受性。利用增殖角质形成细胞对葡萄糖的高需求的方法具有改变银屑病治疗的潜力。
最近关于增强的葡萄糖代谢和葡萄糖转运蛋白 1 在银屑病发病机制中的基本作用的发现揭示了在癌症治疗中已被证明有效的方法。新兴糖缀合物领域的重大进展突出了开发葡萄糖缀合的抗银屑病药物以提高其有效性、细胞选择性和耐受性的合理性。所提出的方法为治疗银屑病和其他过度增殖性皮肤病提供了一种新的治疗策略。
