ASLAN003 (LAS 186323) is a potent and orally active inhibitor of DHODH (Dihydroorotate dehydrogenase) with IC50 of 35 nM for human DHODH enzyme activity. ASLAN003 impairs protein synthesis and induces the differentiation and apoptosis transcriptional program in acute myeloid leukemia (AML) cells via activation of AP-1 transcription factors.

ASLAN003 is a highly potent dihydroorotate dehydrogenase inhibitor that induces differentiation, as well as reducing cell proliferation and viability, of AML cell lines and primary AML blasts including chemoresistant cells. Apoptotic pathways are triggered by ASLAN003, and this drug also significantly inhibits protein synthesis and activates AP-1 transcription, contributing to its capacity to promote differentiation.^[1]

ASLAN003 substantially reduces leukemic burden and prolongs survival in AML xenograft mice and AML patient-derived xenograft models. ASLAN003 has no evident effect on normal hematopoietic cells and exhibits excellent safety profiles in mice, even after a prolonged period of administration.^[1]