WP4 is carried out by Dr. Simon Croft and Dr. Vanessa Yardley at the London School of Hygiene & Tropical Medicine. WP4 will use well-established cell culture and experimental leishmaniasis infection models  to test molecules that were selected by members of the consortium (i.e. partners of WP1, 2, 3 and WP5) and the hit expansion to lead selection. We will establish an iterative cycle based upon rapid and regular interactions between chemists and biologists to select lead compound(s) with selectivity, on-target structure-activity relationships, drug-like properties  and significant in vivo activity in a rodent model. Candidates for hit-to-lead validation include molecules that have already been identified by consortium members (for example cell penetrating peptides with anti-leishmanial activity, partners 8 and 12), and new molecules identified by groups in the consortium through library screens (partners of WP1, WP2, and WP3), in silico approaches or structure/functional analysis (WP6). We will aim to identify at least three classes of compounds that provide hits to proceed to hit expansion on the basis of their efficacy and selectivity.