RGNCY-0114 (LW106 IDO1 inhibitor)

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LW106 is a novel idoleamine 2.3-dioxygenase 1 (IDO1) inhibitor.  IDO1 is emerging as an important new target for the treatment of malignant tumors that are characterized by disregulated tryptophan metabolism.  LW106 was shown to dose-dependently inhibit the outgrowth of xenograft tumors that were incoluated in immunocompetent C57BL6 mice but not nude mice or Ido-/- mice with a stronger antitumor efficacy than epacadostat (an existing IDO1 inhibitor).  LW106 also increased intratumoral infiltration of proliferative Teff cells and reduced recruitment of proiferative Treg cells and non-hematopoietic cells.  LW106 treatment resulted in a reduced subpopulation of cancer stem cells in xenigrafted tmors where fewer proliferative and invasive tumor cells and more apoptotic tumor cells were observed.  IDO1 IC50 = 1.57 µM.

Systematic Name: (E)-(4-amino-1,2,5-oxadiazol-3-yl)(isoindolin-2-yl)methanone oxime

SMILES:  NC1=NON=C1/C(N2CC3=CC=CC=C3C2)=N\O

Formula:  C11H11N5O2

Mol Wt:  245.24

PMID:  29722898