Highly Selective Novel Heme Oxygenase-1 Hits Found by DNA-Encoded Library ML

The heme oxygenase (HO) family comprises the major isozymes HO-1 and HO-2, of which HO-1 is deemed as an emerging target for cancer therapy. HO-1 overexpression is often observed in prostate, renal, colon, lung, breast, and glioma cancers.

In a publication in ACS Med Chem Letters, WuXi AppTec scientists report the discovery of five series of novel scaffold HO-1 inhibitors.  Fourteen tested molecules showed more than 100-fold selectivity towards HO-1 over HO-2. Significantly, this study demonstrates the effectiveness of utilizing extensive DNA-encoded library (DEL) screening data in conjunction with deep learning models for the discovery of novel drug-like hits beyond the conventional DEL chemical space.