TY - JOUR
T1 - Advances in targeting EGFR allosteric site as anti-NSCLC therapy to overcome the drug resistance
AU - Maity, Swastika
AU - Pai, K. Sreedhara Ranganath
AU - Nayak, Yogendra
N1 - Funding Information:
Open access funding provided by Manipal Academy of Higher Education, Manipal. We thank Dr. Pritesh Bhat, Senior scientist, Schrodinger, Bengaluru, for his expert scientific advice in the process of composition of the review article. The Indian Council of Medical Research (ICMR), Government of India, for supporting SM by Granting Senior Research Fellow (No. 45/33/2019-PHA/BMS).
Funding Information:
Open access funding provided by Manipal Academy of Higher Education, Manipal. We thank Dr. Pritesh Bhat, Senior scientist, Schrodinger, Bengaluru, for his expert scientific advice in the process of composition of the review article. The Indian Council of Medical Research (ICMR), Government of India, for supporting SM by Granting Senior Research Fellow (No. 45/33/2019-PHA/BMS).
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/8/1
Y1 - 2020/8/1
N2 - Background: The epidermal growth factor receptor (EGFR) inhibitors represent the first-line therapy regimen for non-small cell lung cancer (NSCLC). Most of these inhibitors target the ATP-site to stop the aggressive development of NSCLC. Stabilization of the ATP-binding on EGFR is difficult due to autophosphorylation of the EGFR domain. This leads to activation of nonintrinsic influence of the tumor microenvironment and expression of anti-apoptotic pathways and drug resistance. Methods: The NSCLC related literature search was carried out using online databases such as Scopus, Web of Sciences, PubMed, Protein Data Bank and UniPort for the last ten years and selected articles are referred for discussion in this review. Results: To overcome the problem of mutations in NSCLC, the allosteric site of EGFR was targeted, which shows significant therapeutic outcome without causing resistance. Compounds like EAI001, EAI045 JBJ-04-125-02, DDC4002 and a series of small molecules with an affinity towards the EGFR allosteric site are reported and are under the investigational stage. These compounds are categorized under fourth-generation anti-NSCLC agents. Conclusion: Composition of this review highlights the advantage of inhibiting allosteric site in the EGFRTK receptor domains and presents a comparative analysis of the new fourth-generation anti-NSCLC agents to overcome the drug resistance.
AB - Background: The epidermal growth factor receptor (EGFR) inhibitors represent the first-line therapy regimen for non-small cell lung cancer (NSCLC). Most of these inhibitors target the ATP-site to stop the aggressive development of NSCLC. Stabilization of the ATP-binding on EGFR is difficult due to autophosphorylation of the EGFR domain. This leads to activation of nonintrinsic influence of the tumor microenvironment and expression of anti-apoptotic pathways and drug resistance. Methods: The NSCLC related literature search was carried out using online databases such as Scopus, Web of Sciences, PubMed, Protein Data Bank and UniPort for the last ten years and selected articles are referred for discussion in this review. Results: To overcome the problem of mutations in NSCLC, the allosteric site of EGFR was targeted, which shows significant therapeutic outcome without causing resistance. Compounds like EAI001, EAI045 JBJ-04-125-02, DDC4002 and a series of small molecules with an affinity towards the EGFR allosteric site are reported and are under the investigational stage. These compounds are categorized under fourth-generation anti-NSCLC agents. Conclusion: Composition of this review highlights the advantage of inhibiting allosteric site in the EGFRTK receptor domains and presents a comparative analysis of the new fourth-generation anti-NSCLC agents to overcome the drug resistance.
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U2 - 10.1007/s43440-020-00131-0
DO - 10.1007/s43440-020-00131-0
M3 - Review article
AN - SCOPUS:85087982202
SN - 1734-1140
VL - 72
SP - 799
EP - 813
JO - Polish Journal of Pharmacology and Pharmacy
JF - Polish Journal of Pharmacology and Pharmacy
IS - 4
ER -
