Texas A&M University has received a USD 1.44 million fiscal year 2026 renewal of an NIH R01 grant from the National Cancer Institute to advance a multiplatform drug discovery program targeting ENL, a chromatin-reading protein implicated in MLL-rearranged acute myeloid leukemia (AML). The award, led by principal investigator Wenshe Ray Liu, funds continued development of small-molecule inhibitors, peptidic inhibitors, and PROTAC degraders aimed at the same target, with the goal of nominating an investigational new drug candidate.
MLL (KMT2A) gene rearrangements, found on chromosome 11q23, drive a subset of AML cases associated with poor prognosis and limited treatment options. ENL, part of the YEATS reader protein family, helps sustain the aberrant gene expression programs underlying this leukemia subtype, making it a genetically validated but chemically challenging target. Liu's group has previously reported a small-molecule inhibitor that extended survival in MOLM-13 xenograft mice, a phage display-derived peptidic inhibitor with cellular activity, and a PROTAC degrader showing selective leukemia cell killing with low toxicity in vitro — preclinical results, not clinical evidence. The renewed funding will support further optimization and pharmacokinetic/pharmacodynamic characterization across all three modalities.
Existing ENL YEATS-targeted small molecules have faced selectivity and metabolic stability issues, and no ENL-directed therapy has reached clinical testing; the funded work sits alongside broader efforts using PROTAC and epigenetic-reader inhibitor strategies across MLL-rearranged leukemias. The multiplatform approach — pursuing small-molecule, peptidic, and degrader modalities against a single target in parallel — reflects a broader shift in academic drug discovery toward diversifying chemical strategies before committing to IND-enabling studies, rather than relying on a single modality.
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