Exploration of Targeted Anti-tumor Therapy

Table 2. 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
Alectinib	November 2017	ALK metastasis	Second
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

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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.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

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Funding

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Copyright

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