In Silico Approaches: A Way to Unveil Novel Therapeutic Drugs for Cervical Cancer Management

被引:29
作者
Gomes, Diana [1 ,2 ,3 ]
Silvestre, Samuel [1 ,4 ,5 ,6 ]
Duarte, Ana Paula [1 ,4 ,6 ]
Venuti, Aldo [7 ]
Soares, Christiane P. [8 ]
Passarinha, Luis [1 ,2 ,3 ,4 ]
Sousa, Angela [1 ]
机构
[1] Univ Beira Interior, CICS UBI Hlth Sci Res Ctr, P-6201506 Covilha, Portugal
[2] Univ NOVA, Fac Ciencias & Tecnol, Inst Hlth & Bioecon, Associate Lab i4HB, P-2819516 Caparica, Portugal
[3] Univ Nova Lisboa, Fac Ciencias & Tecnol, Dept Ciencias Vida, UCIBIO Appl Mol Biosci Unit,Dept Quim, P-2829516 Caparica, Portugal
[4] Univ Beira Interior, Lab Farmacotoxicol UBIMed, P-6200284 Covilha, Portugal
[5] Univ Coimbra, CNC Ctr Neurosci & Cell Biol, P-3004504 Coimbra, Portugal
[6] Univ Beira Interior, UBIMed, C4 Cloud Comp Competence Ctr, Estr Municipal 506, P-6200284 Covilha, Portugal
[7] IRCCS Regina Elena Natl Canc Inst, HPV UNIT UOSD Tumor Immunol & Immunotherapy, I-00144 Rome, Italy
[8] Sao Paulo State Univ UNESP, Sch Pharmaceut Sci, Dept Clin Anal, Campus Ville, BR-14800903 Araraquara, SP, Brazil
关键词
cervical cancer management; computer-aided drug design; E6; inhibitors; in silico studies; human papillomavirus; HUMAN-PAPILLOMAVIRUS E6; INHIBITORS; DEGRADATION; ONCOPROTEIN; IDENTIFICATION; DOCKING; BIOLOGY; BINDING; PROTEIN;
D O I
10.3390/ph14080741
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Cervical cancer (CC) is the fourth most common pathology in women worldwide and presents a high impact in developing countries due to limited financial resources as well as difficulties in monitoring and access to health services. Human papillomavirus (HPV) is the leading cause of CC, and despite the approval of prophylactic vaccines, there is no effective treatment for patients with pre-existing infections or HPV-induced carcinomas. High-risk (HR) HPV E6 and E7 oncoproteins are considered biomarkers in CC progression. Since the E6 structure was resolved, it has been one of the most studied targets to develop novel and specific therapeutics to treat/manage CC. Therefore, several small molecules (plant-derived or synthetic compounds) have been reported as blockers/inhibitors of E6 oncoprotein action, and computational-aided methods have been of high relevance in their discovery and development. In silico approaches have become a powerful tool for reducing the time and cost of the drug development process. Thus, this review will depict small molecules that are already being explored as HR HPV E6 protein blockers and in silico approaches to the design of novel therapeutics for managing CC. Besides, future perspectives in CC therapy will be briefly discussed.
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页数:19
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