p53-y220c

PhiKan 083 hydrochloride, a carbazole derivative, binds to the surface cavity and stabilizes Y220C (Kd: 167 μM) with a relative binding affinity (Kd) of 150 μM in Ln229 cells.

p53-Y220C/PLK1 modulator-1 (compound15) is a regulator of p53-Y220C/PLK1, useful for tumor research.

p53 Activator 7 is a highly potent and cell-permeable activator of the p53 mutation Y220C (MDM-2/p53), which induces apoptosis.

PhiKan 083, a carbazole derivative, exhibits potential as an eco-friendly dye with applications in the development of organic photovoltaic cells (OPVs).

p53 Y220C ligand-1 is the target protein ligand of p53 DUBTAC modulator-1. It demonstrates significant activity in inhibiting the proliferation of Huh7 cells.

MB710 is an amino benzothiazole derivative that binds tightly to the Y220C pocket and stabilizes p53-Y220C in vitro. It exhibits anticancer activity and can be used in cancer research.

MS182 (compound 11), an acetylation targeting chimera (AceTAC), incorporates p53 Y220C stabilizers with p300/CBP binders, connected via a linker. This design enables MS182 to selectively form a ternary complex with p300/CBP acetyltransferase and the mutant p53 Y220C, subsequently catalyzing specific acetylation of lysine at position 382 in a time- and concentration-dependent manner, achieving an ACE 50 of 1.52 μM. Additionally, MS182 demonstrated significant bioavailability in mice, with GI 50 values recorded at 2.16 μM for BxPC3 (p53 Y220C/-) and 1.83 μM for NUGC (p53 Y220C/+).

Antitumor agent-202 is a stabilizer of the p53Y220C mutant, selectively inhibiting the proliferation of tumor cells carrying the p53Y220C mutation. It is applicable for research focused on cancers associated with the p53 Y220C mutation.

PK7242 is an inducer that reactivates mutant p53 in cancer cells. In cancer cells harboring the Y220C mutation, PK7242 binds to the core domain of p53-Y220C, leading to the inhibition of cell growth, cell cycle arrest, and apoptosis.

PMV6-PEG4-BI2536 is a dual-functional compound targeting both p53-Y220C and PLK1. It consists of a high-affinity binder for the p53-Y220C mutant (Kd≈ 2.5 nM) and a potent PLK1 kinase inhibitor (IC50= 0.83 nM). This compound induces G2/M arrest and apoptosis in TP53Y220C cells through PLK1 mislocalization and kinase inhibition, independent of p53 transcriptional reactivation. PMV6-PEG4-BI2536 is applicable for researching TP53 mutant cancers.

p53 Activator 17 is an activator of p53-Y220C. It exhibits selective cytotoxicity and pro-apoptotic (apoptosis) activity in cancer cell lines with the p53-Y220C mutation, with minimal effects on wild-type or p53-null cells. This compound promotes the conversion of intracellular p53-Y220C from a mutant to a wild-type conformation, activating the transcription of classic p53 target genes, including BBC3 (PUMA) and MDM2. p53 Activator 17 is applicable for research on hepatocellular carcinoma and breast cancer.

p53 Activator 16 (Compound JC16) is a p53 activator that shows selective cytotoxicity and pro-apoptotic (apoptosis) activity against cancer cells with the p53-Y220C mutation, while having minimal effects on wild-type or p53-null cells. It induces a conformational change in cellular p53-Y220C from mutant to wild-type, accompanied by transcriptional activation of p53 target genes, without increasing the overall level of p53 protein. p53 Activator 16 is useful for researching p53-mutant cancers.

p53 DUBTAC modulator-1 (Compound A1) is a modulator of the p53 Y220C DUBTAC (Kd = 12.09 µM). It effectively reactivates mutant p53 Y220C and promotes its deubiquitination. This compound upregulates p53 Y220C protein levels, induces apoptosis, reduces Bcl-2 levels, and inhibits the Wnt signaling pathway. Additionally, p53 DUBTAC modulator-1 exhibits anticancer activity against liver cancer.

Rezatapopt analog-1 (PC14586 analog-1) (1919) is an analog of Rezatapopt. It binds to the pocket formed by the TP53 Y220C mutation. Rezatapopt restores the tumor-suppressing function of p53 by stabilizing the structure of the p53 protein.

MB725 is a strong and selective inducer of viability reduction in several cancer cell lines containing the oncogenic p53-Y220C mutation.

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.

SLMP53-2 is a mutant p53 reactivator that restores the wild-type-like conformation and DNA-binding ability of mutp53-Y220C through enhanced interaction with Hsp70, thereby reinstating p53's transcriptional activity. This compound induces cell cycle arrest, apoptosis, and endoplasmic reticulum (ER) stress, displaying antitumor activity [1] [2].

Rezatapopt (PC14586) is a small molecule p53 reactivator with anti-tumor activity that selectively binds to the cleft present in the TP53 Y220C mutant protein and restores the p53 wild-type (normal) conformation and transcriptional activity, and can be used to study locally advanced or metastatic solid tumors.

P53 Activator 11 (compound A-1) is a highly effective p53 activator, demonstrating an EC50 value of 0.478 µM for p53 (Y220C). It holds potential for cancer research [1].