Summary of varied generation ALK-TKI drugs recommended for NSCLC treatment
Drug
Month & year of approval
Circumstantial efficacy screened
Generation stage
Crizotinib
August 2011
ALK metastatic tumors
First
Certinib
April 2014
ALK metastatic tumors
Second
Alectinib
December 2015
Progressed ALK metastatic tumors, exhibiting resistance to crizotinib
Second
November 2017
ALK metastasis
Brigatinib
April 2017
Progressed ALK metastatic tumors, displaying resistance to crizotinib
Second
Ensartinib
Could not be authentically traced
Exhibited 52% ORR in a phase II trial. A phase III trial found ensartinib better than crizotinib in systemic and intracranial diseases. ALK resistance were majorly due to G1269A, G1202R & E1210K mutations
Second
Lorlatinib
November 2018
ALK metastatic tumors treated with alectinib or certinib or crizotinib & at least one more ALK inhibitor
Third
TPX-0131
Currently being investigated
A compact macrocyclic inhibitor that fits well entirely in the ATP binding pocket. Efficient against compound mutations G1202R + L1198F, G1202R + L1196M, L1196M + L1198F, and G1202R + C1156F
Fourth
NVL-655
Currently being investigated
A brain penetrant small molecule inhibitor with significant potential against solvent drug resistance mutations, viz. G1202R, G1202R + L1196M and G1202R + G12269A
Fourth
Declarations
Acknowledgments
The authors would like to thank the School of Chemical Sciences and School of Life Sciences, Central University of Gujarat, ICAR National Research Centre for Equines, Government of India and Amity Institute of Biotechnology for infrastructural and round-the-clock internet facilities.
Author contributions
PM and RR: Conceptualization, Writing—original draft. PM, RR, RS, VHP and TKM: Writing—review & editing. PM and TKM: Validation, Supervision. All authors read and approved the submitted version.
Conflicts of interest
The author declares that there are no conflicts of interest.
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