mutant p53 cancer cells

PK11000 is a p53 targeting compound, has anti-tumor activities through activation of unstable p53.

TRAP-1 (XJZ-06-462) is a p53 transcription activator that effectively activates mutant p53 and triggers the transcription of p53 target genes. In the p53Y220C pancreatic cell line, TRAP-1 rapidly upregulates p21 and other p53 target genes. TRAP-1 also inhibits cell proliferation, exhibiting IC50 values of 3.94 μM and 0.531 μM in BxPC-3 and A549 cell lines, respectively. Additionally, TRAP-1 modulates autophagy in lung cancer cells and provides protection against oxidative stress and apoptosis.

Olomoucine II is an inhibitor of cyclin-dependent kinases (CDKs; IC50s = 7.6, 0.1, 19.8, 0.45, and 0.06 μM for Cdk1, -2, -4, -7, and -9, respectively).1It is selective for CDKs over 10 additional kinases (IC50s = >100 μM for all) but does inhibit ERK2 (IC50= 32 μM) and the ATP-binding cassette transporter B1 (ABCB1; IC50= 6.4 μM).1,2Olomoucine II inhibits proliferation of a variety of cancer cells, including those expressing wild-type p53 or mutant p53 (mean IC50s = 7.4 and 10.1 μM, respectively), and it acts synergistically with daunorubicin to inhibit proliferation of HCT-8 cells that endogenously express ABCB1. Olomoucine also inhibits replication of herpes simplex virus 1 (HSV-1), HSV-2, vaccinia virus, human adenovirus type 4 (Ad4), and human CMV (IC50s = 5, 4.7, 3.8, 2.4, and 3.2 μM, respectively) but not measles virus or influenza virus (IC50s = >20 μM for both).3

CC260, a selective inhibitor for PI5P4Kα and PI5P4Kβ with Kis of 40 nM and 30 nM respectively, exhibits minimal to no inhibition against other protein kinases like Plk1 and RSK2. It is applicable in the research of cell energy metabolism, diabetes, and cancer[1].

The protein p53, often called the 'guardian of the genome,' is a transcription factor that is activated in response to cellular stress (low oxygen levels, heat shock, DNA damage, etc.) and acts to prevent further proliferation of the stressed cell by promoting cell cycle arrest or apoptosis. Its role as a tumor suppressor is evident by the observation that approximately 50% of human tumors have mutated or non-functional p53. PK7242 is an inducer of reactivation of mutant p53 in cancer cells. In cancer cells carrying the Y220C mutant, PK7242 binds to the p53-Y220C core domain and induces growth inhibition, cell-cycle arrest, and apoptosis.

ADH-6, a tripyridylamide compound, impedes the self-assembly of the aggregation-nucleating subdomain of mutant p53 DNA-binding domain (DBD). By targeting and dissociating mutant p53 aggregates in human cancer cells, ADH-6 reinstates p53's transcriptional activity, culminating in cell cycle arrest and apoptosis, thereby holding potential for cancer research.

ADH-6 TFA, a tripyridylamide compound, effectively disrupts the self-assembly of the aggregation-nucleating subdomain of mutant p53 DBD, thereby targeting and disassociating mutant p53 aggregates in human cancer cells. This action restores the transcriptional activity of p53, resulting in cell cycle arrest and apoptosis. Consequently, ADH-6 TFA holds potential for cancer research [1].

BI2536-PEG2-Halo is a bifunctional molecule that integrates a Halo tag ligand with the Polo-like kinase 1 (PLK1) inhibitor BI-2536. This compound selectively exerts cytotoxic effects on mutant p53 cancer cells and inhibits the proliferation of 293T cells expressing the Halo-p53R273H(FL)-mCherry tag, with an IC50 value of 23 nM.