抗肿瘤药物靶蛋白XIAP拮抗剂的硅片设计和筛选

Title:In Silico Designing and Screening of Antagonists against Cancer Drug Target XIAP

Volume: 15 Issue: 9

Author(s): Rahul Kumar, Jagat Singh Chauhan and Gajendra Pal Singh Raghava

Affiliation:

关键词: 化学描述符，肽，定量构效关系，虚拟筛选和主成分，X染色体遗传的细胞凋亡抑制蛋白。

摘要: X-linked inhibitor of apoptosis (XIAP) is a member of inhibitor of apoptosis (IAP) family and involved in the suppression of apoptosis in cancer cells. This property makes it a therapeutic target for the cancer therapy. In the present study, we have developed QSAR models using chemical descriptors, fingerprints, principal components, docking energy parameters and similarity-based approach against XIAP. We have achieved correlation (R) of 0.803 with R² value of 0.645 at 10-fold cross validation using SMOreg algorithm. We have evaluated these models on independent dataset to ascertain its robustness and achieved correlation (R) of 0.793 with R² value of 0.628. Further, we have used these models for the screening of FDA approved drugs and drug-like molecules from ZINC database and prioritized them on the basis of their predicted pIC₅₀ values. Docking studies of top hits with XIAP-BIR3 domain shows that Iodixanol (DB01249) and ZINC68678304 have higher binding affinities than well-known tetrapeptide inhibitor, AVPI. We have integrated these models in a web server named as “XIAPin”. We hope that this web server will contribute in the designing of nifty antagonists against XIAP.

Cite this article as:

Rahul Kumar, Jagat Singh Chauhan and Gajendra Pal Singh Raghava , In Silico Designing and Screening of Antagonists against Cancer Drug Target XIAP , Current Cancer Drug Targets 2015; 15 (9) . https://dx.doi.org/10.2174/1568009615666150706103537