p53/mdm2

RO-5963 is a dual inhibitor of p53-MDM2 and p53-MDMX (IC50s: ~17 nM and ~24 nM, respectively).

Triglycidyl isocyanurate (Teroxirone) is a triazene triepoxide with antineoplastic and antiangiogenic activity. It inhibits growth of human non-small cell lung cancer cells by activating p53. Triglycidyl isocyanurate alkylates and cross-links DNA, thereby inhibiting DNA replication. It induces cell apoptosis and can be used for cancer research[1][2]. Triglycidyl isocyanurate is also used in various polyester powder coatings in the metal finishing industry.

NSC 146109 hydrochloride is an activator of p53 targeting MDMX. NSC 146109 hydrochloride can be used for studies on breast cancer.

BH3I-1 (BHI1) is a Bcl-2 antagonist.

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

NSC 66811is a novel inhibitor of the murine double minute 2 (MDM2)-p53 interaction. It binds to MDM2 with a Ki of 120 nM and activates p53 in cancer cells with a mechanism of action consistent with targeting the MDM2-p53 interaction.

PK11000 is a p53 targeting compound, has anti-tumor activities through activation of unstable p53.

p53-MDM2-IN-7 (compound 6d) (hydrochloride) is an inhibitor of the p53-MDM2 interaction, utilized in anticancer research.

p53-MDM2-IN-2 (Compound 5q) is an orally active p53-MDM2 inhibitor with a Ki value of 0.25 μM. It exhibits antitumor activity by inhibiting the NF-κB pathway.

p53-MDM2-IN-5 (compound 5a), a robust p53-MDM2 inhibitor, effectively induces apoptosis, autophagy, and DNA damage. It also causes cell cycle arrest at the S and G2/M phases and demonstrates anti-tumor activity.

MI-773 (SAR405838 (MI 773)) is an orally available MDM2 antagonist with Ki of 0.88 nM. Phase 1.

Vanillin (Zimco) is a single molecule extracted from vanilla beans and also a popular odor used widely in perfume, food and medicine.Vanillin can reversibly and non-competitively inhibit the cellulase activity at appropriate concentrations and the value of IC50 was estimated to be 30 g/L.Vanillin protects KSC from UVB irradiation and its effects may occur through the suppression of downstream step of MDM2 in UVB irradiation-induced p53 activation. Vanillin also inhibits yeast growth and fermentation.

USP7-IN-4(USP7 inhibitor ALM4) is a non-competitive, potent and selective inhibitor of USP7 (ubiquitin-specific protease 7) with an IC50 = 6 nM, up-regulates p53 and p21, down-regulates MDM2, increases the level of ubiquitination of MDM2, and exhibits anti-proliferative activity in a variety of cancer cell lines, with an EC50 = 2.0 nM in RS4;11 (acute lymphoblastic leukemia cell line) .

FT671 is a non-covalent, selective USP7 inhibitor (IC50=52 nM) that binds to the catalytic domain of USP7 (Kd=7.8 µM). It disrupts the stability of USP7 substrates including MDM2, elevates p53, induces p21, and inhibits tumor growth in mice.

(±)-Darifenacin ((±)-UK-88525) is a potential inhibitor of p53-MDM2 interaction with anticancer activity for the study of overactive bladder, Alzheimer's disease and Parkinson's disease.

BI-0252 is an inhibitor of MDM2-p53 (IC50:4 nM). BI-0252 can induce tumor regressions in all animals of a mouse SJSA-1 xenograft. And it concomitant induction of the tumor protein p53 (TP53) target genes and markers of apoptosis.

RITA (NSC-652287)(NSC-652287) induced cross-links of both DNA-DNA and DNA-protein with no detectable DNA single-strand breaks. RITA, like nutlin-3, can disrupt the p53/Mdm2 interaction.

MMs02943764, a derivative of 1,2,4-triazole, exhibits anticancer activity. This compound demonstrates significant antiproliferative effects across various cancer cell lines. Its structural analog, PAC, shows notable cytotoxicity towards the leukemia cell line K562 (IC50=35.264 μM), functioning by inhibiting Mdm2 and Pirh2 to reduce degradation of p53 and consequently inducing cell cycle arrest in K562 cells.

p53-MDM2-IN-6, an LSM-83177 hydrazone analog, acts as an efficacious p53-MDM2 inhibitor with an IC50 of 11.08 µg/mL. This compound inhibits the p53-MDM2 interaction leading to an increase in p-53 levels while concurrently decreasing GST enzyme expression. It halts the cell cycle at the S phase and induces early and late apoptosis (Apoptosis), exhibiting antiproliferative activity against the HT29 cell line with an IC50 of 10.44 µg/mL. p53-MDM2-IN-6 holds promise for research in colorectal cancer.

Compound MX69-102 is an MDM-2/p53 inhibitor that promotes MDM2 degradation, resulting in the activation of p53 and the apoptosis of cancer cells. It demonstrates effective inhibition against human MDM2-overexpressing ALL xenograft tumors in SCID mice.

WB214 is an MDM2 degrader (IC50 = 1.2 nM). Identified as the most potent antiproliferative agent in various leukemia cell lines, WB214 not only effectively promotes MDM2 degradation but also results in p53 degradation. Further studies demonstrate that WB214 acts as a molecular glue to degrade MDM2. It was ultimately discovered that WB214 efficiently degrades GSPT1, which helps to elucidate its mechanism of cell growth inhibition.

MORINDONE, an anthraquinone compound, exhibits significant binding affinity towards multiple targets including β-catenin, MDM2-p53, and KRAS. It displays notable cytotoxicity and selective activity against colorectal cancer cell lines, and effectively downregulates the expression of mutated TP53 and KRAS genes.

MD-265 is a PROTAC degrader that targets and degrades MDM2, leading to the activation of p53 in cancer cells with wild-type p53. MD-265 achieves complete tumor regression and enhances long-term survival in leukemic mice.

MI-1063 is a DMD-2 inhibitor that prevents the MDM2-p53 interaction and activates p53's tumor-suppressing abilities. It inhibits the growth of cancer cells RS4-11 and MV4-11, with IC50 values of 179 nM and 93 nM, respectively. MI-1063 serves as a target protein ligand for the synthesis of the PROTAC degrader [MD-265].