The first demonstration that abrogation of function of an anti-apoptotic protein by itself could lead to cancer regression was via the use of regulatable expression of BCL-2 in a murine model of leukemia.75 Later work found that deletion of MCL-1 caused regression of a similar MYC-driven lymphoma.58 The first attempt to inhibit the anti-apoptotic proteins was described in 2000 with the discovery of HA14-1, a small molecule targeting the BCL-2 surface pocket that showed activity in vitro. Here, BCL2 is linked to lymphoma.