Project Term
–
Rutgers University
New Brunswick, NJ
United States
Project Summary
KAT7 has recently been identified as an interesting therapeutic target for the treatment of different types of leukemia. However, the only KAT7 inhibitors described to date are either drugs that cannot be used in vivo (WM-3835), or drugs that can be used in vivo but are not really KAT7-specific, as they inhibit KAT6 with even stronger potency (PF-9363).
Thus, using medicinal chemistry approaches we have designed and synthesized novel compounds with the goal of identifying stronger and more specific inhibitors with favorable pharmacokinetic and pharmacodynamic (PK/PD) properties. We already have lead compounds with verified antileukemic effects in vivo, and here we propose to build on their structures with the ultimate goal of obtaining an in vivo active compound that is ~100-fold more potent against KAT7 than KAT6A with favorable ADME and PK/PD properties, which could be moved into clinical trials in the short term.
Lay Abstract
We and others have identified a protein, KAT7, that is very relevant for leukemia cells, such that KAT7 inhibitors should confer strong antileukemic effects and could be a novel therapeutic strategy for leukemia patients.
However, the KAT7 inhibitors described so far are not good enough to be used in patients.
Thus, our goal is to achieve a KAT7 inhibitor drug more potent than the already described drugs but that, more importantly, has favorable chemical properties to allow for its use in patients, as such drug could revolutionize leukemia treatment.
In our series of initial compounds already synthesized, we have detected 2 that are stronger than previously published drugs, and with favorable chemical properties, but to really allow for their use in patients we still need to develop even better compounds. Thus, based on the structures of our 2 lead compounds, we proposed to generate a clinical-grade KAT7-specific inhibitor that could be used in leukemia patients in the short term.
Program