erlotinib

P3, N=453, Active, not recruiting, Eli Lilly and Company | Trial completion date: Dec 2025 --> Dec 2026

P3, N=390, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2026 --> Feb 2027 | Trial primary completion date: Oct 2026 --> Dec 2025

It exhibited superior activity compared to the reference drug erlotinib, with a cellular IC₅₀ of 4.35 μM vs 11.83 μM and an EGFR enzymatic IC₅₀ of 105.96 nM vs 218.47 nM, indicating approximately 2-fold enhanced potency...Mechanistic investigations demonstrated that 6E increased ROS generation, induced mitochondrial depolarisation, and promoted apoptotic cell death. Further, molecular docking and MD simulations of the 6E-EGFR complex highlighted key amino acid interactions, corroborating the observed in vitro EGFR inhibition.

The initial HTVS (high-throughput virtual screening), followed by XP analysis and molecular mechanics (MMGBSA) and ADME profiling, led to the identification of Cycloguanil (antimalarial) and Metformin (antidiabetic) as the putative lead molecules with the potential to inhibit the EGFR...Cycloguanil inhibited the EGFR with a half maximal inhibitory concentration (IC50) of IC50 of 490 nM compared to erlotinib with an IC50 of 222 nM...From the analysis, it was deduced that cycloguanil exhibited the most potent cytotoxicity towards the A549 cell with an IC50 of 6.83 μM, followed by HCT-116 with an IC50 of 9.32 μM, while in MCF-7, it exhibited an IC50 of 14.82 μM. The lead molecule, cycloguanil, may plausibly serve as an important template that may be optimized by performing bioisosteric replacements, leading to a putative kinase inhibitor with a potent anticancer profile.

P1/2, N=44, Not yet recruiting, Northwestern University | Trial completion date: Jun 2030 --> Jun 2031 | Trial primary completion date: Jun 2030 --> Jun 2031

Compounds 12, 17, 27, 43, 45, and 49 demonstrated strong binding affinities and superior pharmacokinetic profiles compared to Gefitinib and Erlotinib. Overall, benzothiazole derivatives represent a promising scaffold for the design of EGFR inhibitors, potentially contributing to targeted anticancer therapy.

P=N/A, N=4864, Completed, Brigham and Women's Hospital | Active, not recruiting --> Completed | Trial completion date: Jan 2025 --> Nov 2025 | Trial primary completion date: Jan 2025 --> Nov 2025

This in silico study predicts Carteolol as a potential dual-targeting therapeutic agent, requiring biochemical and cellular validation before clinical relevance can be established.

P2, N=168, Completed, Eli Lilly and Company | Active, not recruiting --> Completed

P1, N=85, Active, not recruiting, Boundless Bio | Recruiting --> Active, not recruiting | N=127 --> 85

Compounds 4a and 4g were the most potent EGFR inhibitors (IC50  = 0.09 µM and 0.10 µM, respectively), compared to the standard erlotinib (IC50 = 0.16 µM)...This binding interaction likely contributes to their significant biological activity. Further, dynamic stimulation study that is conducted for compounds 4a and 4g, supports their potency as therapeutic agents in cancer treatment.

Cassia-derived flavonoids represent promising multi-target candidates for lung cancer therapy, particularly through modulation of PTGS2, KIT, and XDH. Their favorable interaction profiles and safety predictions warrant further experimental and in vivo validation.