Combination of menin and FLT3 inhibitors is very effective in AML models. Read in Blood.
Here is our review on epigenetic protein-protein interactions with Brian as first author
We reported MI-3454, a very potent menin inhibitor. See our JCI paper.
# news not updated
We published paper "Property focused structure-based optimization of small molecule inhibitors of the protein-protein interaction between menin and Mixed Lineage Leukemia (MLL)" in the Journal of Medicinal Chemistry.
We determined structure of ZMIZ1 TPR domain and published paper in collaboration with Mark Chiang: The PIAS-like Coactivator Zmiz1 Is a Direct and Selective Cofactor of Notch1 in T Cell Development and Leukemia. Published in Immunity.
Our manuscript "Two loops undergoing concerted dynamics regulate activity of the ASH1L histone methyltransferase" has been published in Biochemistry.
Our study "Rational design of orthogonal multipolar interactions with fluorine in protein-ligand complexes" has been published in Journal of Medicinal Chemistry, selected as Editor's choice.
Felicia Gray defended her PhD thesis: "Dissecting Bmi1 protein-protein interactions through chemical biology". Congratulations Felicia!
We have published study demonstrating that menin-MLL inhibitors block activity of MLL fusion proteins in a mechanism independent on fusion partner. Published in Leukemia.
George Lund defended his PhD dissertation: "Targeting CDC25B-CDK2/CyclinA Activity Using Chemical Biology Approaches".
Our menin-MLL inhibitor program has been featured as cover story in BioCentury Innovations
Dr. Chinnaiyan's lab discovered role of menin and demonstrated efficacy of menin inhibitors in castrate resistant prostate cancer. Study published in Nature Medicine.
Our team work resulted in development of potent inhibitors of menin-MLL interaction with strong efficacy in animal models of leukemia. Published in Cancer Cell.
We have licensed menin-MLL inhibitors to Kura Oncology for further development.
Jola is co-author on study to develop small molecule inhibitors of CBFB-SMMHC: "A small-molecule inhibitor of the aberrant transcription factor CBFβ-SMMHC delays leukemia in mice" published in Science.
We published review Targeting protein–protein interactions in hematologic malignancies: still a challenge or a great opportunity for future therapies? in Immunological Reviews
Our study Inhibition of CDC25B Phosphatase Through Disruption of Protein-Protein Interaction has been published in ACS Chemical Biology.
Nov 17, 2014
Jola has been elected to the University of Michigan Medical School "League of Research Excellence". Congratulations to Jola!
Our study "The same site on LEDGF IBD domain represents therapeutic target for MLL leukemia and HIV" has been published in Blood.
Apr 21, 2014
George's publication "Solution NMR studies reveal no global flexibility in the catalytic domain of CDC25B" has been published in the journal Proteins.
Congratulations to George!
Our review "Challenges and opportunities in targeting the menin-MLL interaction" has been published in Future Medicinal Chemistry
Discovery and Development of Small Molecules for Targeted Therapies in Cancer
The focus of the Grembecka/Cierpicki laboratories is discovery and development of small molecules for targeted therapies in cancer. Targeted cancer therapies use drugs that selectively inhibit growth of cancer cells by blocking proteins directly involved in cancer cell division and spread. By focusing on inhibiting proteins directly involved in molecular and cellular changes that are specific to cancer, targeted cancer therapies are more effective and much less harmful to normal cells than other types of treatment, such as chemotherapy or radiotherapy.
We are particularly interested in development of small molecules targeting epigenetic proteins involved in leukemia and solid cancers and in assessing their activity and mechanism of action in in vitro and in vivo models of cancer. We developed potent inhibitors of the menin-MLL interaction as a novel therapy for leukemias with MLL-rearrangements and NPM1 mutations. We are also developing inhibitors of histone methyltransferases, including NSD1 and ASH1L with activities in leukemia models. Our work has also been focused on targeting cancer stem cells via inhibition of the PRC1 complex.
The research in Grembecka/Cierpicki lab. is high interdisciplinary, and includes medicinal chemistry combined with biochemical, structural biology, biological and animal studies with an overreaching goal to develop drug-like compounds and evaluate their efficacy in pre-clinical models of cancer for their future translation to the clinic.