Figure 2.

The experiment and observation-based diagram of the FL118’s mechanisms of action (MOA). (1) Use of FL118 affinity purification approach, followed by alternative confirmation, DDX5 was identified as the FL118 direct biochemical target, which was demonstrated being very important for human PDAC and CRC tumors. Our studies relevant to PDAC and CRC revealed that the previously identified FL118 downstream targets (e.g., survivin, Mcl-1, XIAP, cIAP2, etc.) are the downstream targets of DDX5. Additionally, FL118 could bypass additional treatment resistant factors (efflux pump proteins ABCG2 and Pgp, mutated Kras, mutated p53 and mutated APC). (2) Our collaboration studies also revealed that the bone marrow stromal cells-rendered MM cell resistance to CAR T cells or NK cells can be abrogated by FL118 treatment; therefore, it would be attractive for FL118 in combination with immunotherapy for treatment of resistant cancers.