Menin-MLL protein-protein interaction inhibitors: a patent review (2021-present).

Introduction: Acute leukemia harboring rearrangement of the Mixed lineage leukemia (MLL) and/or mutation of the nucleophosmin is a type of poorly prognostic and highly malignant leukemia which is extremely difficult to treat. Blocking the protein-protein interaction between Menin and MLL is a strategic approach for treating leukemias, as a new direction for drug discovery. Many biotech and pharmaceutical companies made great efforts to this drug development field, and a large number of small molecular Menin-MLL PPI inhibitors were reported during the recent three years.

Discovery of novel pyrrolo[2,3-d]pyrimidines as potent menin-mixed lineage leukemia interaction inhibitors.

To interfere the Menin-MLL interaction using small molecular inhibitors has been shown as new treatment of several special hematological malignancies. Herein, a series of Menin-MLL interaction inhibitors with pyrrolo[2,3-d]pyrimidine scaffold were designed, synthesized and evaluated. Among them, compound A6 exhibited potent binding affinity with an IC value of 0.

Discovery of novel pyrido[3,2-d]pyrimidine derivatives as selective and potent PI3Kδ inhibitors.

The δ isoform of class I PI3K (PI3Kδ) has been shown as a promising target for the treatment of hematologic malignancies and immune diseases. Herein, a series of pyrido[3,2-d]pyrimidine derivatives were designed, synthesized and evaluated for the preliminary bioactivity. Compared with idelalisib, compound S5 exhibited excellent enzyme activity against PI3Kδ (IC  = 2.

Discovery of Novel, Potent, and Selective Small-Molecule Menin-Mixed Lineage Leukemia Interaction Inhibitors through Attempting Introduction of Hydrophilic Groups.

Introduction of the ,-dimethylaminoethoxy group to pyrido[3,2-]pyrimidine led to the discovery of menin-mixed lineage leukemia (MLL) interaction inhibitor . showed strong binding affinity to menin protein and achieved sub-micromolar potency in cell growth inhibition. had good selectivity for the inhibition of the interaction between menin and MLL in the kinase profile evaluation.

Menin-MLL protein-protein interaction inhibitors: a patent review (2014-2021).

Introduction: Chromosomal translocations involving the mixed-lineage leukemia (MLL, KMT2A, MLL1) genes result in the production of MLL fusion proteins, which cause abnormal transcriptional regulation leading to acute leukemia (AL). Menin (MEN1) protein is essential for MLL to regulate the expression of related target genes. High-affinity interactions between the amino terminus of MLL proteins and Menin proteins are required to mediate the oncogenic transformation of MLL fusion proteins.

Small molecule selenium-containing compounds: Recent development and therapeutic applications.

Selenium (Se) is an essential micronutrient of organism and has important function. It participates in the functions of selenoprotein in several manners. In recent years, Se has attracted much attention because of its therapeutic potential against several diseases.