Indoleamine 2,3-dioxygenase 1 (IDO1) is a key target for the development of small molecule immunotherapies in oncology. In this framework, the screening of chemotherapeutic agents to identify compounds binding to IDO1 represents a valuable strategy for the development of multitarget drug candidates that combine synergic immunoregulatory properties to cytotoxic activity. In this study, we report that two natural compounds endowed with anticancer activity, namely lapachol and auraptene, act as IDO1 ligands with dissociation constant (Kd) in the micromolar range of potency. Docking studies provide plausible binding modes of these compounds to the catalytic cleft of IDO1. Our results support the notion that lapachol and auraptene may be considered interesting lead compounds in the immuno-oncology setting.
Microscale thermophoresis and docking studies suggest lapachol and auraptene are ligands of IDO1
Fiorito S.;Greco F. A.;Coletti A.;Dolciami D.;Grohmann U.;Macchiarulo A.
2018
Abstract
Indoleamine 2,3-dioxygenase 1 (IDO1) is a key target for the development of small molecule immunotherapies in oncology. In this framework, the screening of chemotherapeutic agents to identify compounds binding to IDO1 represents a valuable strategy for the development of multitarget drug candidates that combine synergic immunoregulatory properties to cytotoxic activity. In this study, we report that two natural compounds endowed with anticancer activity, namely lapachol and auraptene, act as IDO1 ligands with dissociation constant (Kd) in the micromolar range of potency. Docking studies provide plausible binding modes of these compounds to the catalytic cleft of IDO1. Our results support the notion that lapachol and auraptene may be considered interesting lead compounds in the immuno-oncology setting.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
