Synergy and antagonism between azacitidine and FLT3 inhibitors
Synergetic interactions between drugs can produce a drug combination more efficient. Alternatively, they might let it use lower concentrations and therefore avoid toxicities or negative effects that does not only cause discomfort but can also lessen the overall survival. Here, we studied whether synergy exists between agents that can be used for management of acute myeloid leukaemia (AML). Azacitidine is really a demethylation agent which is used in treating AML patients which are unfit for aggressive chemotherapy. An activating mutation within the FLT3 gene is typical in AML patients and even without the specific treatment makes prognosis worse. FLT3 inhibitors can be utilized in such instances. We searched for to find out whether mixture of azacitidine having a FLT3 inhibitor (gilteritinib, quizartinib, LT-850-166, FN-1501 or FF-10101) displayed synergy or antagonism. For this finish, we calculated dose-response matrices of those drug combinations from experiments in human AML cells and subsequently analysed the information utilizing a novel consensus scoring formula. The outcomes reveal that combinations that involved non-covalent FLT3 inhibitors, such as the two clinically approved drugs gilteritinib and quizartinib were hostile. However combinations using the covalent inhibitor FF-10101 had some selection of concentrations where synergy was observed.