p53

JNJ-26854165 is one of p53-activating agents and synergizes with AraC or doxorubicin to induce p53-mediated apoptosis and may provide a novel therapeutic approach for the treatment of acute leukemias.

RG7112 is the first clinical small-molecule MDM2 inhibitor designed to occupy the p53-binding pocket of MDM2.

RITA, also referred to as NSC 652287, is a trycyclic thiophene derivative that binds to MDM2, disrupting the MDM2-p53 complex and subsequently activating p53 and inducing apoptosis.

Tenovin-1 is a small molecule activator of p53 transcriptional activity that protects against MDM2-mediated p53 degradation.

Tenovin-6 is a analog of tenovin-1. Tenovin-6 inhibits the protein deacetylase activities of purified human SIRT1, SIRT2, and SIRT3 in vitro with IC50 values of 21, 10, and 67 uM, respectively.

inhibits p53 binding to mitochondria by reducing its affinity for antiapoptotic proteins Bcl-2 and Bcl-XL.

Pifithrin-beta is a small molecule inhibitor of p53.

Pifithrin-α hydrobromide is a reversible inhibitor of p53-mediated apoptosis and p53-dependent gene transcription such as cyclin G, p21/waf1, and mdm2 expression.

NSC 319726 is a potent and selective activator of mutant p53R175

NSC348884 is a nucleolar phosphoprotein that displays several biological activities in ribosome biogenesis, cell proliferation, cytoplasmic/nuclear shuttle transportation, nucleic acid binding, ribonucleic cleavage, and centrosome duplication. NSC 348884 is a putative inhibitor of nucleophosmin (NPM). NSC 348884 inhibits NMP oligomer formation, up-regulates p53 and induces apoptosis.

NSC59984 induces mutant p53 protein degradation via MDM2 and the ubiquitin-proteasome pathway. The EC50 of NSC59984 in most cancer cells is significantly lower than those of normal cells, with EC50 of 8.38 uM for p53-null HCT116 cells.

CP 31398 has been shown to act as a stabilizing agent for p53, and to promotes activity of p53 in cancer cell lines.

PRIMA-1 is a small molecule identified for its p53 reactivating effect.

APR-246 is a quinuclidinone derivative that targets the Wrap53 gene with potential antineoplastic activity.

Tenovin-3 is a sirtuin inhibitor.

Kevetrin (thioureidobutyronitrile), is a water-soluble, small molecule and activator of the tumor suppressor protein p53, with potential antineoplastic activity.

Idasanutlin is a potent and selective p53-MDM2 inhibitor.

p53 and MDM2 proteins-interaction-inhibitor chiral is an inhibitor of the interaction between p53 and MDM2 proteins.

p53 and MDM2 proteins-interaction-inhibitor racemic is an inhibitor of the interaction between p53 and MDM2 proteins.

CP 31398 dihydrochloride, p53 stabilizing agent. Stabilizes the active conformation of p53 and promotes p53 activity in cancer cell lines with mutant or wild-type p53. Inhibits growth of small human tumor xenografts in vivo.

MIRA-1 restores wild-type conformation, function and DNA binding activity to mutant p53. Induces p53 transcriptional transactivation of p21, MDM2 and PUMA.

NSC 146109 hydrochloride is a cell-permeable, genotype-selective antitumor agent that activates p53-dependent transcription.

PhiKan 083, p53 stabilizing agent; preferentially binds mutated (Y220C) p53 over wild-type p53 at a site distinct from functional DNA/protein interaction regions.

RETRA hydrochloride is an antitumor agent which inhibits tumor cell growth in a mutant p53- and p73-dependent manner in vitro and iin vivo.

SJ 172550 is the first MDMX inhibitor with EC50 of 0.84 uM; binds reversibly to MDMX and effectively kills retinoblastoma cells in which the expression of MDMX is amplified.

WR 1065, a dephosphorylated metabolite of amifostine (Ethyol), can protect against the immediate and delayed effects of radiation exposure.

PK11000 is an anti-p53 drug that stabilizes wild type and mutant p53 via selective alkylation of two surface-exposed cysteines without compromising its DNA binding activity. It exerts antitumor functions not only via reactivating p53 but also via other cellular mechanisms, such as increase of cellular ROS to toxic levels and activation of the UPR.

CBL0137 hydrochloride activates p53 and inhibits NF-kB with EC50s of 0.37 μM and 0.47 μM in the cell-based p53 and NF-kB reporter assays, respectively. It also inhibits histone chaperone FACT (facilitates chromatin transcription complex).

COTI-2 is an orally available thiosemicarbazone that activates mutant forms of p53. It induces apoptosis in a wide variety of human tumor cells in culture, inhibits the proliferation of colorectal cancer cell lines, and is active against human glioblastoma cell lines at nanomolar concentrations.

CBL0137 is a FACT inhibitor that functionally inactivates the facilitates chromatin transcription complex (FACT), driving the effects on p53 and NF-κB and promoting cancer cell death.

Amifostine is a phosphorothioate proposed as a radiation-protective agent. It causes splenic vasodilation and may block autonomic ganglia.

BI-0252 is an orally active, selective MDM2-p53 inhibitor with an IC50 of 4 nM.

Minocycline hydrochloride is a broad-spectrum tetracycline antibiotic, acting by binding to the bacterial 30S ribosomal subunit and inhibiting protein synthesis.

PhiKan 083 hydrochloride is a carbazole derivative, which binds to the surface cavity and stabilizes Y220C (a p53 mutant), with a Kd of 167 μM, and a relative binding affinity (Kd) of 150 μM in Ln229 cells.

Pifithrin-β (PFT β) is a potent p53 inhibitor with an IC50 of 23 μM.

Triglycidyl isocyanurate (TGIC; Teroxirone) is a triazene triepoxide with antiangiogenic and antineoplastic activities.

Solasodine (also known as Purapuridine) is a steroidal alkaloid found in plants of the Solanaceae family. It induces apoptosis by inhibiting the p53–MDM2 complex and downregulating p21^Waf1/Cip1 and Bcl-2 proteins. Solasodine exhibits a range of biological activities, including neuroprotective, antifungal, hypotensive, anticancer, antiatherosclerotic, antiandrogenic, and anti-inflammatory effects.

SDU-071 is a potent, orally active inhibitor targeting the BRD4-p53 interaction. It inhibits the proliferation of MDA-MB-231 cells with an IC₅₀ of 10.5 μM and induces cell cycle arrest and apoptosis.

ReACp53 is a cell-penetrating peptide that inhibits p53 amyloid aggregation, restoring p53 function in cancer cell lines and organoids derived from high-grade serous ovarian carcinoma (HGSOC).

C16-Ceramide is a natural small molecule that acts as a p53 activator by directly and selectively binding to the protein. This compound is known to induce apoptosis in various cancer cell lines, making it a valuable tool for research in cancer biology and therapeutic development. Its ability to modulate p53 activity facilitates investigations into cellular stress responses and the mechanisms underlying tumor suppression.

p-nitro-Pifithrin-α is a potent inhibitor of the p53 tumor suppressor protein. This cell-permeable compound effectively suppresses p53-mediated TGF-β1 expression in HK-2 kidney cells and prevents the activation of caspase-3 induced by Zika virus strains. Additionally, p-nitro-Pifithrin-α demonstrates protective effects against steatosis and liver injury in high-fat diet models, positioning it as a valuable tool in the study of non-alcoholic fatty liver disease and p53-related pathways.

PAWI-2 is a p53 activator and Wnt inhibitor that targets β3-KRAS signaling independently of KRAS. This compound selectively inhibits the phosphorylation of TBK1, resulting in the activation of apoptotic pathways, evidenced by increased caspase-3/7 activity and PARP cleavage. Additionally, PAWI-2 facilitates the translocation of optineurin into the nucleus and induces G2/M cell cycle arrest. It effectively reverses cancer stemness and overcomes drug resistance in integrin β3 KRAS-dependent human pancreatic cancer stem cells, demonstrating significant tumor growth inhibition in orthotopic xenograft mouse models.

DPBQ is a potent p53 activator that promotes apoptosis specifically in polyploid cells. It induces the expression and phosphorylation of p53 without inhibiting topoisomerase or directly binding to DNA. This selective action makes DPBQ a valuable tool for research involving polyploidy and the modulation of p53 signaling pathways.

STIMA-1 is a p53 activator that stimulates mutant p53 DNA binding in vitro. This compound induces the expression of p53 target proteins and promotes apoptosis in human tumor cells expressing mutant p53. It serves as a valuable tool for researching p53-driven pathways and potential therapeutic strategies for cancers associated with p53 mutations.

Condurango glycoside A is a potent p53 activator that initiates reactive oxygen species (ROS) generation and up-regulates p53 expression. This compound effectively induces apoptosis and promotes premature senescence associated with DNA damage in HeLa cells. Its biological activity makes it a valuable tool for research focused on cellular stress responses and cancer biology.

MI-1061 TFA is a potent inhibitor of the MDM2-p53 interaction, exhibiting an IC50 of 4.4 nM and a Ki of 0.16 nM. This orally bioavailable and chemically stable compound effectively activates p53, leading to apoptosis in SJSA-1 xenograft tumor tissues in murine models. MI-1061 TFA demonstrates significant anti-tumor activity, making it a valuable tool for cancer research focused on the modulation of the p53 signaling pathway.

DS-5272 is an orally active inhibitor of the p53-MDM2 interaction, demonstrating an IC50 of 20 nM. This compound effectively inhibits the proliferation of SJSA-1 cells (wildtype p53, IC50 = 0.17 μM) as well as DLD-1 cells (mutant p53). DS-5272 induces cell cycle arrest and promotes apoptosis in SJSA-1 cells, while also exhibiting antitumor efficacy in vivo in mouse models. This makes DS-5272 a valuable tool for research in cancer therapeutics targeting the p53 pathway.

Seldegamadlin is a selective p53 stabilizer and an MDM2 PROTAC degrader with a DC50 of 0.4 nM. It effectively inhibits the proliferation of RS4;11 cancer cells, demonstrating an IC50 of 0.3 nM, and induces cell cycle arrest at the G2/M phase while promoting apoptosis. By upregulating p53 activity, Seldegamadlin overcomes the p53-MDM2 feedback loop, making it a valuable tool for research in hematologic and solid tumors, including acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL).

SLMP53-2 is a mutant p53 reactivator that restores the wild-type conformation and DNA-binding capabilities of the mutp53-Y220C variant by enhancing its interaction with Hsp70. This mechanism reestablishes p53 transcriptional activity, contributing to important biological processes such as cell cycle arrest, apoptosis, and endoplasmic reticulum (ER) stress. SLMP53-2 demonstrates significant antitumor activity, making it a valuable tool for research in cancer biology and therapeutic development.

TRAP-1 is a selective p53Y220C transcriptional activator that engages with p53Y220C and BRD4 to form a ternary complex, leading to enhanced transcription of mutant p53 target genes. It effectively upregulates p21 and other p53 target genes in pancreatic cell lines harboring the p53Y220C mutation. Notably, TRAP-1 demonstrates significant antiproliferative effects, exhibiting IC50 values of 0.531 μM in BxPC-3 cells (p53Y220C) compared to 3.94 μM in A549 cells (p53WT). TRAP-1 is a valuable tool for investigating cancer associated with the p53Y220C mutation.