Calmirasone1 (Calmirasone 1) is a novel and potent covalent calmodulin (CaM) inhibitor with Kd of 0.87 uM.
Calmirasone1 shows potency in 3D spheroids with IC50 value of 12 uM (MDA-MB-231) and 5.2 uM (Hs 578T).
Calmirasone1 has a 4-fold increased affinity for CaM as compared to OphA (Ophiobolin A) and was active against K-Ras in cells within minutes, as compared to hours required by OphA.
Calmirasone1 displayed a 2.5-4.5-fold higher selectivity for KRAS over BRAF mutant 3D spheroid growth than OphA.
Calmirasone1 has a 40-260-fold lower unspecific toxic effect on HRAS mutant cells, while it reaches almost 50% of the activity of novel K-RasG12C specific inhibitors in 3D spheroid assays.
