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.

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.

Pifithrin-beta is a small molecule inhibitor of p53.

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.

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.

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

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

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

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.

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.

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.

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

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.

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.

p53 Stabilizer 2 (Compound 17a16) is a potent p53 stabilizer that enhances the stability and function of the p53 protein. This compound induces S-phase arrest and apoptosis in both p53-proficient and p53-deficient cancer cells, demonstrating its broad therapeutic potential. Mechanistically, p53 Stabilizer 2 triggers mitochondrial stress and activates critical checkpoint pathways, including NA-PKcs-dependent p53 stabilization and ATR-Chk1 axis activation. Additionally, it has shown efficacy in inhibiting tumor growth in p53-deficient xenograft models, making it a valuable tool for cancer research.

TDP-665759 is a p53 activator that functions by inhibiting the HDM2:p53 complex, thereby promoting p53 activity. It exhibits significant inhibition of the STAT3 signaling pathway with an EC50 of 5.90 μM and reduces cell viability in p53-expressing A549R cells, demonstrating an IC50 of 7.02 μM. TDP-665759 has also been shown to induce apoptosis in HepG2 cells and displays antitumor efficacy in mouse models, making it a valuable tool for cancer research and therapeutic development.

p53-MDM2-IN-6 is a selective inhibitor of the p53-MDM2 interaction, demonstrating an IC50 of 11.08 µg/mL. This compound effectively induces cell cycle arrest in the S phase and promotes both early and late apoptosis in HT29 colorectal cancer cell lines, with an IC50 of 10.44 µg/mL. Its ability to elevate p53 levels while decreasing GST enzyme expression highlights its potential as a valuable tool for investigating therapeutic strategies in colorectal cancer research.

p53-MDM2-IN-5 is a potent inhibitor of the p53-MDM2 interaction. This compound induces apoptosis, promotes autophagy, and causes DNA damage in cells, contributing to its anti-tumor efficacy. Additionally, p53-MDM2-IN-5 effectively induces cell cycle arrest at both the S and G2/M phases, making it a valuable tool for cancer research applications focused on therapeutic strategies targeting the p53 pathway.

p53 Activator 14 is a potent activator of the p53 tumor suppressor pathway. This compound induces DNA damage, resulting in the activation of p53 and subsequent inhibition of proliferation in various cancer cell lines, with an IC50 of 7.21 μM in HCT116 cells. Additionally, it demonstrates the ability to inhibit cell adhesion, migration, and invasion, while also inducing cell cycle arrest and apoptosis. Its anti-angiogenic properties and antitumor efficacy have been validated using the chick chorioallantoic membrane (CAM) model, showcasing its potential for cancer research applications.

MI-773 TFA is a selective inhibitor of the MDM2-p53 interaction, demonstrating a Ki of 0.88 nM for MDM2. By disrupting the MDM2-TP53 interaction, MI-773 TFA effectively activates the p53 tumor suppressor pathway, leading to apoptotic cell death. This compound has shown significant anticancer activity, inducing tumor regression in xenograft models of adenoid cystic carcinoma and exhibiting therapeutic potential in neuroblastoma. MI-773 TFA serves as a valuable tool for research focused on p53-related cancer therapies.

YL-1-9 is a potent inhibitor of p53 degradation mediated by MDM2, achieved through its strong binding to critical hydrophobic pockets within the MDM2 protein. This compound effectively induces cell cycle arrest and promotes apoptosis, particularly in breast cancer cells. YL-1-9 is valuable for research into p53-targeted therapies and the mechanisms of cancer cell proliferation and survival.

NSC194598 is a p53 DNA-binding inhibitor that effectively disrupts the interaction between p53 and DNA, exhibiting an IC50 value of 180 nM for in vitro studies and a range of 2-40 μM for in vivo applications. This compound has been shown to interfere with the transcriptional activation of the mutated RET gene in human medullary thyroid carcinoma TT cells. NSC194598 is utilized in research investigating acute toxicity effects on normal tissues due to radiation and chemotherapy.

Roslin 2 bromide, also known as Benzylhexamethylenetetramine bromide, is a reactivator of the p53 tumor suppressor protein. By binding to focal adhesion kinase (FAK), Roslin 2 bromide disrupts the interaction between FAK and p53, thereby enhancing p53 activity and exhibiting potential anticancer effects. This compound is suitable for research applications focused on cancer biology and the modulation of p53 signaling pathways.

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).

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.

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

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.

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.

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