A fragment-like approach to PYCR1 inhibition.

•Higher levels of protein are found in certain types of cancer.•This is attributed to overexpression of a key protein involved in proline biosynthesis.•Focused screening has for the first time identified a small fragment-like inhibitor (ProPI-1) of this protein target.•Mechanistic studies show ProPI-1 can attenuate proline biosynthesis in relevant cell types.•Phenotypic studies reveal that ProPI-1 can control cell proliferation in two different breast cancer cell types.