BACKGROUND: Acute myeloid leukemia is the collective name for different types of 
leukemias of myeloid origin affecting blood and bone marrow. The overproduction 
of immature myeloblasts (white blood cells) is the characteristic feature of 
AML, thus flooding the bone marrow and reducing its capacity to produce normal 
blood cells. USFDA on August 1, 2017, approved a drug named Enasidenib formerly 
known as AG-221 which is being marketed under the name Idhifa to treat R/R AML 
with IDH2 mutation. The present review depicts the broad profile of enasidenib 
including various aspects of chemistry, preclinical, clinical studies, 
pharmacokinetics, mode of action and toxicity studies.
METHODS: Various reports and research articles have been referred to summarize 
different aspects related to chemistry and pharmacokinetics of enasidenib. 
Clinical data was collected from various recently published clinical reports 
including clinical trial outcomes.
RESULT: The various findings of enasidenib revealed that it has been designed to 
allosterically inhibit mutated IDH2 to treat R/R AML patients. It has also 
presented good safety and efficacy profile along with 9.3 months overall 
survival rates of patients in which disease has relapsed. The drug is still 
under study either in combination or solely to treat hematological malignancies. 
Molecular modeling studies revealed that enasidenib binds to its target through 
hydrophobic interaction and hydrogen bonding inside the binding pocket. 
Enasidenib is found to be associated with certain adverse effects like elevated 
bilirubin level, diarrhea, differentiation syndrome, decreased potassium and 
calcium levels, etc.
CONCLUSION: Enasidenib or AG-221was introduced by FDA as an anticancer agent 
which was developed as a first in class, a selective allosteric inhibitor of the 
tumor target i.e. IDH2 for Relapsed or Refractory AML. Phase 1/2 clinical trial 
of Enasidenib resulted in the overall survival rate of 40.3% with CR of 19.3%. 
Phase III trial on the Enasidenib is still under process along with another 
trial to test its potency against other cell lines. Edasidenib is associated 
with certain adverse effects, which can be reduced by investigators by designing 
its newer derivatives on the basis of SAR studies. Hence, it may come in the 
light as a potent lead entity for anticancer treatment in the coming years.