HLI373 is an Efficacious Hdm2 Inhibitor, with Antimalarial Activity
Hdm2 is an ubiquitin-protein ligase. Hdm2 suppresses the transcriptional activity of the tumor suppressor p53 and promotes its degradation. HLI373 is an efficacious Hdm2 inhibitor. HLI373 is effective in inducing apoptosis of several tumor cell lines that are sensitive to DNA-damaging agents. These results suggest that HLI373 could serve...
CMLD010509 is a Highly Specific Inhibitor of the Oncogenic MYC-Driven Translation Program
Multiple myelomas (MM) is a hematological malignancy, it exhibits a clonal proliferation of plasma cells in the bone marrow micro-environment. MM remains a frequently incurable hematological malignancy until today. MYC can directly enhance transcription genes encoding ribosomal proteins, ribosomal RNA, and proteins of the translation initiation complex. Furthermore, most...
MD-224 is a First-in-Class and Highly Potent PROTAC Degrader of MDM2
As previously introduced, the tumor suppressor p53 plays a critical role in the prevention of tumor development. While human, murine double minute 2 (MDM2) protein is a primary endogenous cellular inhibitor of the tumor suppressor p53. And it has been pursued as a promising cancer therapeutic target. A study...
MI-1061 is an Orally Active MDM2 Inhibitor
Inhibition of the MDM2-p53 protein-protein interaction is being actively pursued as a new anticancer therapeutic strategy. Our previous blogs have introduced typical MDM2 or MDM2-p53 inhibitors, including MI-773, RG7112, and AMG 232. Today, I would like to mention another MDM2 inhibitor MI-1061 came from a study from Aguilar A....
RG7112 is the First Clinical and Orally Active MDM2-p53 Inhibitor
Yesterday, I introduced AMG 232 as a potent, selective and orally available inhibitor of p53-MDM2 interaction. Additionally, we have known the significance of MDM2-p53 interaction in cancer development. Today, I’d like to introduce another orally available MDM-2-p53 intreraction inhibitor, RG7112. RG7112 binds selectively to the p53 pocket on the...
BI-0252 is an Orally Active Inhibitor of the MDM2-p53 Interaction
The tumor protein p53 is a pivotal tumor suppressor protein and a mainstay of the body’s cellular anti-cancer defense system. As a potent transcription factor, TP53 regulates multiple downstream target genes implicated in cell-cycle control, apoptosis, senescence, and DNA repair. In particular, tumor protein p53 (TP53) is one of...
APG-115, an Orally Active MDM2 Inhibitor, Induces Cell-Cycle Arrest and Apoptosis in a p53-Dependent Manner
The essential all human cancers compromises the tumor suppressor function of p53. In about half of human cancers, TP53, the gene encoding p53 protein, is mutated or deleted. This inactivates the tumor suppressor function of p53. In the remaining 50%, p53 retains its wild-type status. But, murine double minute 2 (MDM2)...