SHMT1 and neoplasm: To investigate the effect of serine deprivation on tumour cell proliferation we targeted three potential sources of serine: (i) serine import, (ii) serine synthesis from glycine via SHMT1 and 2 and (iii) de novo synthesis via PHGDH by employing glycine- and serine-free DMEM as well as the novel small-molecule PHGDH inhibitor CBR-5884.30 The combination of glycine- and serine-free DMEM with 60 μM CBR-5884 resulted in a significantly reduced intracellular serine and glycine level in comparison to vehicle in G55 cells (Fig. 2a).