PMID- 32276580
OWN - NLM
STAT- MEDLINE
DCOM- 20210702
LR  - 20210702
IS  - 1538-0254 (Electronic)
IS  - 0739-1102 (Linking)
VI  - 39
IP  - 8
DP  - 2021 May
TI  - BREED based de novo hybridization approach: generating novel T790M/C797S-EGFR 
      tyrosine kinase inhibitors to overcome the problem of mutation and resistance in 
      non small cell lung cancer (NSCLC).
PG  - 2838-2856
LID - 10.1080/07391102.2020.1754918 [doi]
AB  - Third generation EGFR inhibitor osimertinib was approved as the first-line 
      treatment for EGFR T790M mutation-positive Non-Small Cell Lung Cancer (NSCLC) 
      patients in 2017. However, EGFR tertiary Cys797 to Ser797 (C797S) point mutation 
      emanate rapidly after treatment of osimertinib, which is undruggable mutation to 
      the all existing drugs. In this work, we have reported the novel T790M/C797S-EGFR 
      Tyrosine Kinase inhibitors using BREED based de novo hybridization approach. 
      BREED generates novel inhibitors from structures of known ligands bound to a 
      common target. Among the generated hybridised breed compounds, the top best 
      scorer breed molecules were breed 436, breed 530, breed 450, breed 562 and breed 
      313. Molecular Dynamics simulation of breed 436 for 10 ns further suggested that 
      docked compound was stable into the pocket of the T790M/C797S-EGFR Tyrosine 
      Kinase. In silico pharmacokinetic predictions of the breed hybridised compounds 
      were within the defined range described for human use.Communicated by Ramaswamy 
      H. Sarma.
FAU - Patel, Harun M
AU  - Patel HM
AD  - Division of Bioinformatics, Department of Pharmaceutical Chemistry, R.C. Patel 
      Institute of Pharmaceutical Education and Research, Maharashtra, India.
FAU - Shaikh, Matin
AU  - Shaikh M
AD  - Division of Bioinformatics, Department of Pharmaceutical Chemistry, R.C. Patel 
      Institute of Pharmaceutical Education and Research, Maharashtra, India.
FAU - Ahmad, Iqrar
AU  - Ahmad I
AUID- ORCID: 0000-0002-7697-9572
AD  - Division of Bioinformatics, Department of Pharmaceutical Chemistry, R.C. Patel 
      Institute of Pharmaceutical Education and Research, Maharashtra, India.
FAU - Lokwani, Deepak
AU  - Lokwani D
AD  - Division of Bioinformatics, Department of Pharmaceutical Chemistry, R.C. Patel 
      Institute of Pharmaceutical Education and Research, Maharashtra, India.
FAU - Surana, Sanjay J
AU  - Surana SJ
AD  - Division of Bioinformatics, Department of Pharmaceutical Chemistry, R.C. Patel 
      Institute of Pharmaceutical Education and Research, Maharashtra, India.
LA  - eng
PT  - Journal Article
DEP - 20200423
PL  - England
TA  - J Biomol Struct Dyn
JT  - Journal of biomolecular structure & dynamics
JID - 8404176
RN  - 0 (Aniline Compounds)
RN  - 0 (Protein Kinase Inhibitors)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - Aniline Compounds
MH  - *Carcinoma, Non-Small-Cell Lung/drug therapy/genetics
MH  - Drug Resistance, Neoplasm/genetics
MH  - ErbB Receptors/genetics
MH  - Humans
MH  - *Lung Neoplasms/drug therapy/genetics
MH  - Mutation
MH  - Protein Kinase Inhibitors/pharmacology
OTO - NOTNLM
OT  - ADME
OT  - T790M/C797S-EGFR tyrosine kinase
OT  - breed
OT  - simulation
EDAT- 2020/04/12 06:00
MHDA- 2021/07/03 06:00
CRDT- 2020/04/12 06:00
PHST- 2020/04/12 06:00 [pubmed]
PHST- 2021/07/03 06:00 [medline]
PHST- 2020/04/12 06:00 [entrez]
AID - 10.1080/07391102.2020.1754918 [doi]
PST - ppublish
SO  - J Biomol Struct Dyn. 2021 May;39(8):2838-2856. doi: 
      10.1080/07391102.2020.1754918. Epub 2020 Apr 23.