p53-mutant

UC2288 is a relatively selective p21 attenuator which is synthesized based Sorafenib. UC2288 attenuates p21 protein levels with minimal effect on p21 protein stability.

BAY 1892005 is a p53 protein modulator that targets the p53 condenser for the study of diseases associated with misfolded p53 protein

NSC-697923 (2-[(4-methylphenyl)sulfonyl]-5-nitrofuran), a potent inhibitor of UBE2N (ubiquitin-conjugating enzyme E2 N, Ubc13), exhibits its role in inducing cell death in neuroblastoma (NB) cells through two distinct mechanisms. In p53 wild-type NB cells, NSC-697923 promotes the nuclear importation of p53, thereby triggering cell death. Meanwhile, in p53 mutant NB cells, NSC-697923 activates the JNK-mediated apoptotic pathway, leading to cell death. Additionally, NSC-697923 inhibits DNA damage and NF-κB signaling, further contributing to its antitumor activity.

USP7-797 is a selective non-covalent active site USP7 inhibitor, inhibiting USP7 and ubiquitin binding, with anti-tumor, oral and high efficiency (IC50=0.44 nmol), it is effective on both wild-type and mutant p53 tumor cells, and can significantly inhibit the growth of tumor cells and induce apoptosis.

CP-31398 dihydrochloride is a p53 stabilizer which stabilizes the active conformation of p53 and promotes p53 activity in cancer cell lines with mutant or wild-type p53.

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/+).

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.

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.

YX-02-030M is a PROTACMDM2 degrader. It inhibits the binding of MDM2 to p53 and VHL to HIF1α, with IC50 values of 63 nM and 1.35 μM, respectively. YX-02-030M binds to MDM2 and recruits the VHL E3 ubiquitin ligase to initiate MDM2 degradation, effectively killing p53 mutant or deficient triple-negative breast cancer (TNBC) cells.

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.

MD-4251 is an orally active MDM2 PROTAC degrader. It potently degrades MDM2 in RS4;11 cells (DC50: 0.2 nM) and activates p53. MD-4251 exhibits strong antiproliferative activity against acute leukemia cells with wild-type p53, but shows limited efficacy in mutant cells. In RS4;11 xenograft mouse models, MD-4251 induces complete tumor regression.

Isogranulatimide is a selective inhibitor of checkpoint kinase 1 (Chk1), with an IC50 of 0.1 μM. It can inhibit the G2/M checkpoint and suppress the growth of p53-mutant tumor cells. Isogranulatimide holds potential for research in tumors associated with DNA damage response.

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.

BW-AQ-113 is a derivative of Anthraquinone that specifically degrades MDM2 and activates the p53 pathway. It exhibits IC50 values of 0.12 μM in Molt-4 cells and 0.2 μM in EU-1 cells. In p53-deficient K562 cells, p53-mutant T98G cells, and p53-inhibited HeLa cells, its IC50 values are 0.74, 5.2, and 2.1 μM, respectively. BW-AQ-113 induces apoptosis by downregulating the anti-apoptotic gene Bcl-2 and upregulating pro-apoptotic genes Bax and CASP3. Additionally, BW-AQ-113 can be utilized in research on hematologic malignancies with wild-type p53.

Kevetrin hydrochloride (4-Isothioureidobutyronitrile hydrochloride) is a small molecule and activator of the tumor suppressor protein p53, with potential antineoplastic activity.

Olomoucine II is a potent cyclin-dependent kinase inhibitor with IC50 values of 7.6, 0.1, 19.8, 0.45, and 0.06 μM for CDK1, CDK2, CDK4, CDK7, and CDK9, respectively. Olomoucine II demonstrates high selectivity over numerous other kinases while retaining measurable activity against ERK2 and ABCB1, allowing it to modulate multidrug resistance pathways. Olomoucine II suppresses proliferation across cancer cell lines regardless of p53 status and exhibits synergistic action with daunorubicin in ABCB1-expressing HCT-8 cells.Olomoucine II additionally inhibits replication of HSV-1, HSV-2, vaccinia virus, adenovirus 4, and human CMV, making Olomoucine II an important antiviral and anticancer research tool.

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.

SCH529074 is a selective activator of p53 (Ki = 1 μM) and can be used in studies about non-small-cell lung carcinoma. SCH529074 restores mutant p53 function and interrupts HDM2-mediated ubiquitination of wild Type p53.

COTI-2, an orally available thiosemicarbazone, is an activator of mutant forms of the p53 protein with potential antineoplastic activity.

Eprenetapopt (PRIMA-1Met) restores wild-type conformation and function to mutant p53, and triggers apoptosis in tumor cells. PRIMA-1MET also targets the selenoprotein thioredoxin reductase 1 (TrxR1), a key regulator of cellular redox balance.