Figure 2.

Chlorine substitution affects toxicity and directs lead compound development. MG87 RET/GFRa1- and TrkA-expressing cells were exposed to 1 μm compounds in regular growth media and assessed by MTT. Q2003 and Q2004 bearing a hydrogen in place of the chlorine were not toxic, indistinguishable from vehicle control (Veh.). However, Q1047, the chlorine-containing analogue of Q2003, showed significant signs of toxicity under the same conditions. Additionally, the lack of toxicity observed by Q525 demonstrated that the chlorine could be maintained and directed the development of more potent, RET-selective leads. The comparable toxicity between both cell lines indicated that the origin of the toxicity is not due to RET overactivation but rather a generalized mechanism.