TY - GEN
T1 - Novel inhibitors of T315I mutant BCR-ABL1 tyrosine kinase for chronic myeloid leukemia disease through fragment-based drug design
AU - Anindita, Satya
AU - Marnolia, Atika
AU - Putra, Hersal Hermana
AU - Haikal, Muhammad Chandra
AU - Tambunan, Usman Sumo Friend
N1 - Publisher Copyright:
© Springer International Publishing AG, part of Springer Nature 2018.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
KW - BCR-ABL1
KW - CML
KW - Docking
KW - Fragment-based
UR - http://www.scopus.com/inward/record.url?scp=85050359926&partnerID=8YFLogxK
U2 - 10.1007/978-3-319-94968-0_17
DO - 10.1007/978-3-319-94968-0_17
M3 - Conference contribution
AN - SCOPUS:85050359926
SN - 9783319949673
T3 - Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
SP - 185
EP - 190
BT - Bioinformatics Research and Applications - 14th International Symposium, ISBRA 2018, Proceedings
A2 - Zhang, Fa
A2 - Zhang, Shihua
A2 - Cai, Zhipeng
A2 - Skums, Pavel
PB - Springer Verlag
T2 - 14th International Symposium on Bioinformatics Research and Applications, ISBRA 2018
Y2 - 8 June 2018 through 11 June 2018
ER -