Navitoclax ABT

Gandhi L et al (2011) Phase I study of Navitoclax (ABT-263), a novel Bcl-2 family inhibitor, in patients with small-cell lung cancer and other solid tumors. J Clin Oncol 29(7) 909-916... 

Ultimately, a select few compounds with combinations of the best functional groups were compared in various animal efficacy and PK/PD models. On the basis of these studies, 27 was chosen as the next development candidate, ABT-263, which was later renamed navitoclax [73]. As is summarized in Fig. 6, at the former nitro and phenyl positions, both potency and various pharmacokinetic inputs were improved, while the morpholine sacrificed some of the gained potency for a more critical further improvement in oral absorption. The end result is a compound with very similar activity to ABT-737, but a much improved pharmacokinetic profile. 

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