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3D-QSAR Study on Imidazopyridazines Derivatives as Potent Pim-1 Kinase Inhibitors using Region-Focused CoMFA

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Author(s)
Pavithra K. Balasubramanian Anand Balupuri Seung Joo Cho
Issued Date
2017
Keyword
Pim-1 Region-focused CoMFA Imidazopyridazine Derviatives Kinase Inhibitors
Abstract
Proviral Integration site of Moloney (Pim) murine Leukemia virus kinases is a serine/threonine specific protein kinase. It is largely involved in cell survival and proliferation. Pim-1 phosphorylates multiple cellular substrates to inhibit apoptosis and promote cell cycle progression. Over expression of Pim-1 kinase is observed in a range of malignancies and various solid cancers. High level of Pim-1 expression is seen in myeloma, acute myeloid leukemia, prostate cancer and liver carcinomas. Hence, Pim-1 is considered as an interesting cancer target. In the present study, we have performed region-focused CoMFA study on a series of imidazopyridazine derivatives as Pim-1 kinase inhibitors. A statistically acceptable region-focused CoMFA model ($q^2=0.571$ 수식 이미지; ONC=3; $r^2=0.909$ 수식 이미지) was developed. The model was then validated using Bootsrapping and progressive sampling. The contour map highlighted the regions favorable to increase the activity. Bulky substitutions in $R^2$ 수식 이미지 position of the phenyl ring could increase the activity. Similarly, small negative substitution in the $R^1$ 수식 이미지 position of the Pyridine ring could increase the activity considerably. Our results will be useful to design novel Pim-1 kinase inhibitors of this series.
Publisher
조선대학교 기초과학연구원
Citation
Pavithra K. Balasubramanian. (2017). 3D-QSAR Study on Imidazopyridazines Derivatives as Potent Pim-1 Kinase Inhibitors using Region-Focused CoMFA, 조선자연과학논문집 | Vol.10, No.2 p.95 ~ p.104
Type
Laboratory article
ISSN
2005-1042
URI
https://oak.chosun.ac.kr/handle/2020.oak/17269
http://www.chosun.ac.kr/user/indexSub.do?codyMenuSeq=24427455&siteId=ricns&dum=dum&boardId=175013&page=1&command=list&categoryId=266502&categoryDepth=0011
Appears in Collections:
2017 > Vol.10, No.2
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