First-in-class, selective, drug-like small molecule MEIS inhibitors
MEIS family of proteins are found to be important regulators of homeostasis. Studies in the last decade have shown that Meis1 has crucial roles in cardiac regeneration, stem cell function, and tumorigenesis. MEIS proteins are associated with limited cardiac regeneration, limited stem cell proliferation and cancer progression.
MEIS proteins could be therapeutically targeted to develop therapies for cardiovascular diseases, bone failure, and cancer. Meis1 was first discovered in BXH-2 mouse leukemia model. Studies in the last decade have shown that Meis1 has crucial roles in cellular metabolism, redox state, and tumorigenesis. Meis1 maintains cytoplasmic glycolysis through transactivation of hypoxic tumor markers, namely Hif-1α and Hif-2α. MEIS1 along with other homeobox proteins (PBX and HOXA) often found to be driving hematopoietic transformation in MLL-rearranged leukemia and described as an oncogene. Intriguingly, a high level of Meis1 expression was found to be associated with resistance to conventional chemotherapies (Reviewed in Current drug targets).