Novel inhibitors of T315I mutant BCR-ABL1 tyrosine kinase for chronic myeloid leukemia disease through fragment-based drug design

Satya Anindita, Atika Marnolia, Hersal Hermana Putra, Muhammad Chandra Haikal, Usman Sumo Friend

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review

1 Citation (Scopus)

Abstract

The hallmark genetic abnormality of CML is named Philadelphia chromosome. Philadelphia chromosome occurs as a result of recombination of two genes, namely the cellular ABL gene on chromosome 9 and BCR gene located on chromosome 22. The Philadelphia chromosomal translocation is responsible for the ABL and BCR fusion. The ABL and BCR proteins play a central role in the pathogenesis of CML. The malignant transformation by BCR-ABL is critically dependent on its protein tyrosine kinase activity. It makes ABL kinase is an attractive target for therapeutic intervention. In this research, about 653,214 leadlike compounds were obtained from MOE database. The compounds were screened using Data Warrior v.4.6.1 and also docked to predict their binding affinity to BCR-ABL1 tyrosine kinase protein using MOE 2014.09 software. Fragment-based drug design was applied to find a new drug candidate. Finally, five new compounds were generated from this method. The compound LUT-1 has the highest potential due to the low ΔG binding score, acceptable RMSD score, and ADME-Tox result.

Original languageEnglish
Title of host publicationBioinformatics Research and Applications - 14th International Symposium, ISBRA 2018, Proceedings
EditorsFa Zhang, Shihua Zhang, Zhipeng Cai, Pavel Skums
PublisherSpringer Verlag
Pages185-190
Number of pages6
ISBN (Print)9783319949673
DOIs
Publication statusPublished - 1 Jan 2018
Event14th International Symposium on Bioinformatics Research and Applications, ISBRA 2018 - Beijing, China
Duration: 8 Jun 201811 Jun 2018

Publication series

NameLecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
Volume10847 LNBI
ISSN (Print)0302-9743
ISSN (Electronic)1611-3349

Conference

Conference14th International Symposium on Bioinformatics Research and Applications, ISBRA 2018
Country/TerritoryChina
CityBeijing
Period8/06/1811/06/18

Keywords

  • BCR-ABL1
  • CML
  • Docking
  • Fragment-based

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