Small molecule, mutant epidermal growth factor receptor kinase (mEGFR) inhibitors are rendered ineffective in NSCLC due to mutations within the enzyme binding sites and redundant signaling pathways. The mEGFR inhibitors were found to retain their anticancer effects in NSCLC cells if given concurrently with AURK inhibitors. Dual-targeted small molecules designed to inhibit both mEGFR and AURK could demonstrate improved anticancer effects compared to monotargeted mEGFR inhibitors. We conducted molecular modeling studies to determine if there were similarities between the kinase pockets of mEGFR and AURK that could be exploited to develop dual-targeted mEGFR and AURK inhibitors. An overlap was observed for the active and allosteric sites of the kinase pocket for mEGFR and AURK. A series of compounds were synthesized and evaluated against mEGFR, AURKA, and AURKB. We found the kinase inhibitory profile to vary significantly depending on the substitution pattern ranging from selective mEGFR inhibitors to dual mEGFR and AURK inhibitors. The 4-substituted amino-N-phenylbenzamides were identified as dual mEGFR/AURK inhibitors. Dual mEGFR/AURK inhibitors demonstrated varied modes of binding within mEGFR and AURK. The most potent dual mEGFR and AURK inhibitors displayed nanomolar inhibition of mEGFR and AURK, and single-digit micromolar inhibition of non-small cell lung cancer cells. Target compounds were further evaluated in a 96-kinase screening assay and demonstrated selectivity for target kinases. The synthesis, structure-activity relationship (SAR) analysis and anticancer effects will be presented and discussed. Citation Format: Brianne Rogers, Nicholas Rohde, Justin Mikitaroff, Joshua Matson, Samantha Satawa, Felix Amissah, Sonali Kurup. 4-Amino-N-phenylbenzamides as dual-targeted mEGFR and AURK inhibitors and anticancer agents. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5339.