a, A chemical genetic screen to identify suppressors of the crestin+ lineage during embryogenesis identified NSC210627, a compound which completely abrogates expression by ISH (a, left and middle). The Discoverygate chemoinformatic algorithm revealed structural similarity between NSC210627 and brequinar (see ), an inhibitor of dihydroorotate dehydrogenase (DHODH). Leflunomide, a structurally distinct DHODH inhibitor, phenocopies the crestin phenotype of NSC210627 (a, right). b-d, Leflunomide caused an absence of multiple neural crest derivatives, including pigmented melanocytes (b), mitf-GFP+ melanocyte progenitors (c), and mbp-mCherry+ glial cells (d). e, Leflunomide or A771726 (see ) significantly reduced the number of multipotent daughter cells that could be subcloned from individual primary neural crest stem cell colonies (Values shown are mean +/-SD of n=3 replicates; *, p<0.05 compared to control, t-test).