The 19 unique products observed in crystals (Fig. ) have the same binding mode defined by the starting fragment, referred as the lateral pose (Fig. ). Iter 1.0, the exploration of the urea vector, was the only singlestep iteration to yield ten follow-up crystal hits on the XChem platform (Fig. ). Three of the binding events were from overlapping compounds from Iter 1.0. The importance of the furan ring for binding was highlighted when no structural hits were found for Iter 1.1's urea vector exploration where the furan ring was not included (Fig. ). Iter 2.0 highlighted the importance of retaining the urea group of the initial fragments; no hits were found unless retained . Structurally, the urea group forms a hydrogen bond with the proline 1340 backbone oxygen (Fig. ).