AURKA-IN-4 is a Capsaicin -derived molecular glue targeting AURKA-PHB2, and acts as an inhibitor of Aurora kinase A ( AURKA ) and PHB2. AURKA-IN-4 binds to the active site of AURKA and the inhibitory pocket of PHB2, inhibits AURKA -dependent mitophagy, and increases mitochondrial mass in cancer cells overexpressing AURKA. AURKA-IN-4 can be used in the research of breast cancer [1].
In Vitro, AURKA-IN-4 (compound 13) (5-50 μM; 6 h) significantly enhances and stabilizes the protein-protein proximity between AURKA and PHB2 in MCF7 breast cancer cells[1]. AURKA-IN-4 (50 μM; 6 h) does not alter the activation status of AURKA in centrosomes of MCF7 breast cancer cells[1]. AURKA-IN-4 acts as a molecular glue to stabilize the AURKA/PHB2/LC3 ternary complex, and its binding affinity to AURKA (Ki=10.86 μM) is higher than that to PHB2 (Ki=248.14 μM)[1]. AURKA-IN-4 (50 μM; 24 h) specifically inhibits AURKA-dependent mitophagy in MCF7 and T47D breast cancer cells with overexpressed AURKA, increases mitochondrial mass, but exerts no effect on Hs578T cells with low endogenous AURKA levels[1].
References:
[1]. Djehal A, et al. Development of capsaicin-derived prohibitin ligands to modulate the Aurora kinase A/PHB2 interaction and mitophagy in cancer cells. Communications biology. 2026 Jan 24;9(1):320.
In Vitro, AURKA-IN-4 (compound 13) (5-50 μM; 6 h) significantly enhances and stabilizes the protein-protein proximity between AURKA and PHB2 in MCF7 breast cancer cells[1]. AURKA-IN-4 (50 μM; 6 h) does not alter the activation status of AURKA in centrosomes of MCF7 breast cancer cells[1]. AURKA-IN-4 acts as a molecular glue to stabilize the AURKA/PHB2/LC3 ternary complex, and its binding affinity to AURKA (Ki=10.86 μM) is higher than that to PHB2 (Ki=248.14 μM)[1]. AURKA-IN-4 (50 μM; 24 h) specifically inhibits AURKA-dependent mitophagy in MCF7 and T47D breast cancer cells with overexpressed AURKA, increases mitochondrial mass, but exerts no effect on Hs578T cells with low endogenous AURKA levels[1].
References:
[1]. Djehal A, et al. Development of capsaicin-derived prohibitin ligands to modulate the Aurora kinase A/PHB2 interaction and mitophagy in cancer cells. Communications biology. 2026 Jan 24;9(1):320.