mutant p53 cancer cells

PK11000 是一种烷化剂，可通过共价半胱氨酸修饰来稳定野生型和突变型p53的 DNA 结合结构域。

TRAP-1 (XJZ-06-462) 作为一种p53转录激活剂，能够有效地在突变p53中触发p53靶基因的转录活性。在胰腺细胞系p53Y220C中，该化合物能迅速提高p21等p53靶基因的表达水平。此外，TRAP-1 在BxPC-3和A549细胞线中显示出抑制细胞增殖的效果，其半抑制浓度(IC50)分别为3.94和0.531 μM。该化合物还能促进肺癌细胞的自噬作用，并在氧化应激和细胞凋亡方面提供保护。

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 is a selective PI5P4Kα and PI5P4Kβ inhibitor with Kis of 40 nM and 30 nM, respectively. CC260 does not inhibit or weakly inhibits other protein kinases, such as Plk1 and RSK2. CC260 can be used for cell energy metabolism, diabetes and cancer research[1]. In cultured C2C12 myotubes, CC260 (20 μM) enhances Insulin-induced Akt phosphorylation at both Thr-308 and Ser-473 but suppresses S6K phosphorylation (Thr-389) by mTORC1[1]. CC260 (2.5 μM, 5 μM, 10 μM, 20 μM) significantly increases phosphorylation of acetyl-CoA carboxylase (ACC) in a dose-dependent manner[1]. CC260 treatment reduces the ability of BT474 cells to survive serum starvation, which could be rescued by expressing the PI5P4Kβ refractory mutant[1]. In BT474 cells, CC260 treatment causes an increase in glycolytic ATP production[1]. [1]. Song Chen, et al. Pharmacological inhibition of PI5P4Kα β disrupts cell energy metabolism and selectively kills p53- tumor cells. Proc Natl Acad Sci U S A. 2021 May 25;118(21):e2002486118.

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-6，一种三吡啶酰胺化合物，消除突变p53 DBD聚集成核亚结构域的自组装，并靶向解离人类癌细胞中的突变p53聚集体。通过此过程，ADH-6恢复p53的转录活性，导致细胞周期停滞与细胞凋亡(apoptosis)，展示了其研究癌症疾病的潜力。

ADH-6 TFA为三吡啶酰胺类化合物，通过靶向并解离人类癌细胞中突变p53聚集体，阻止突变p53 DBD聚集成核亚结构域的自组装，从而恢复p53的转录活性。这一过程导致细胞周期停滞和细胞凋亡(apoptosis)，显示出其在研究癌症疾病中的应用潜力。

BI2536-PEG2-Halo 是一种结合了 Polo-like kinase 1 (PLK1) 抑制剂 BI-2536 和 Halo 标签配体的双功能分子.这种化合物在 293T 细胞中,含有 Halo-p53R273H(FL)-mCherry 标签的版本,其抑制增殖的 IC50 值为 23 nM,显示出针对 p53 突变的癌细胞具有选择性的毒性.