Cell-Based Identification of New IDO1 Modulator Chemotypes

Hennes E, Lampe P, Dötsch L, Bruning N, Pulvermacher LM, Sievers S, Ziegler S, Waldmann H (2021) Angew Chem Int Ed Engl 

10. Februar 2021
The immunoregulatory enzyme IDO1 strengthens cancer immune escape. The Waldmann lab and the Ziegler lab developed a new, robust fluorescence-based assay amenable to high throughput, which detects kynurenine in cells, a product of IDO1 activity. Screening of a 150,000-member compound library discovered unprecedented, potent IDO1modulators with different mechanisms of action, including direct IDO1 inhibitors, regulators of IDO1 expression and inhibitors of heme synthesis. Three IDO1-modulator chemotypes were identified that bind to apo-IDO1 and compete with the heme cofactor. This new cell-based technology opens up novel opportunities for medicinal chemistry programs in immuno-oncology.
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