2023 World Conference on Lung Cancer (Posters)-P2.09. Design, Synthesis and Assessment of Novel Molecule against Drug-Resistant Dual Mutant EGFR (T790M/L858R) to Treat NSCLC

P2.09. Design, Synthesis and Assessment of Novel Molecule against Drug-Resistant Dual Mutant EGFR (T790M/L858R) to Treat NSCLC - PDF(Slides)

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Researchers have developed a small molecule inhibitor called KKI04 to treat non-small cell lung cancer (NSCLC) that is resistant to current treatments. The inhibitor targets dual mutant EGFR (T790M/L858R) mutations, which account for over 85% of mutations in NSCLC that lead to drug resistance. KKI04 has shown to be more effective than current EGFR drugs in inhibiting both the molecular and cellular levels of EGFR activity. In cell viability assays, KKI04 demonstrated superior performance compared to Osimertinib, Erlotinib, and Gefitinib, with lower IC50 values. The molecule was also found to induce apoptosis in NSCLC cells, with higher potency compared to Osimertinib. <br /><br />The researchers used lead optimization to identify KKI04 as the most potent candidate against drug-resistant EGFR mutations. They also conducted protein expression and purification using the Baculovirus expression system. The study involved various types of lung cancer cells, including A431 (EGFR overexpressed) cells, H1975 (T/L dual mutant) cells, and A549 cells (lung cancer cells). The efficacy of KKI04 was evaluated through cell viability assays, protein purification, and molecule identification.<br /><br />The findings indicate that KKI04 has the potential to enhance patient outcomes and treatment strategies for NSCLC with acquired resistance to EGFR drugs. Preclinical studies are currently being conducted to further assess the therapeutic potential of KKI04, including in vivo experimentation using mouse models to evaluate toxicity, pharmacokinetics, and antitumor activity. The researchers acknowledge the grant support received from DST, ICMR, and DBT. Overall, this study presents a promising step forward in the development of novel treatments for drug-resistant NSCLC.

Asset Subtitle

Vikas Kumar

Meta Tag

Speaker Vikas Kumar

Topic Metastatic NSCLC: Targeted Therapy - EGFR/HER2

Keywords

small molecule inhibitor

KKI04

non-small cell lung cancer

NSCLC

drug resistance

EGFR mutations

cell viability assays

apoptosis

lead optimization

protein expression