mdm-2/p53

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) .

D-CopA3 is an inhibitor of MDM2 and an activator of the p53 signaling pathway. It exhibits cytotoxicity in colorectal cancer cells HCT-116, LoVo, and RKO with IC50 values of 15-18 μM and induces JNK Beclin-1 mediated autophagy. D-CopA3 downregulates the expression of the cell cycle inhibitor protein p21Cip1 Waf1, enhances mucosal barrier function, and reduces infiltration of inflammatory mediators. It shows anti-inflammatory properties in mouse models of acute enteritis induced by C. difficile toxin A and chronic colitis induced by DSS. Additionally, D-CopA3 demonstrates antitumor activity in a mouse HCT-116 xenograft model.

HL001 is an orally active small molecule inhibitor of cyclophilin A (CypA) and a receptor antagonist of lysophosphatidic acid 1 (LPA1). It induces cell cycle arrest and apoptosis in tumor cells via p53. By downregulating G3BP1, HL001 promotes reactive oxygen species production and DNA damage to stabilize p53. It disrupts the interaction between MDM2 and p53-72R in a CypA-dependent manner. HL001 exhibits antitumor activity and can also be used in research on pulmonary fibrosis.

p53 Activator 14 (Compound 7A) is a derivative of Neratinib that can induce DNA damage and activate p53, thereby inhibiting the proliferation of various cancer cells, with an IC50 of 7.21 μM for HCT116 cells. This compound hinders adhesion, migration, and invasion of HCT116 cells, disrupts the cell cycle, and triggers apoptosis. In addition, p53 Activator 14 exhibits anti-tumor properties and inhibits angiogenesis in the chick embryo chorioallantoic membrane (CAM) model.

NA-17 is a naphthalimide compound with antitumor activity and exhibits lower toxicity to normal cells such as HL-7702 and WI-38. It demonstrates p53-dependent inhibition selectivity in various NSCLC cells, inducing the accumulation of active p53 in the mitochondria and nuclei of these cells. NA-17 causes cell cycle arrest in the G1 phase and promotes apoptosis and cell death.

MDM2ligand 4 is a ligand of MDM2 and can be used in the synthesis of the PROTAC degrader [KT-253].

BRD6257 is an orally active inhibitor of protein phosphatase 1D (proteinphosphatase, Mg2+ Mn2+ dependent 1D, PPM1D) with an IC50 of 5 nM. It activates the p53 signaling pathway (EC50 of 51 nM), enhances p21 expression, and inhibits the proliferation of cancer cells MOLM13 (IC50 = 2.8 μM). BRD6257 demonstrates good metabolic stability in human and rat liver microsomes.

4-Hydroxyresveratrol (3,4,5,4'-Tetrahydroxystibene) is a resveratrol analog that variably induces the expression of pro-apoptotic genes such as p53 and Bax. It triggers apoptosis in SV40 virus-transformed WI38 cells (WI38VA), but not in WI38 cells. Additionally, 4-Hydroxyresveratrol significantly increases the expression of p53, GADD45, and Bax genes in WI38VA cells, while suppressing the expression of the bcl-2 gene.

FMP is a platinum (IV) complex. It significantly upregulates the expression of γ-H2AX and p53, enhances ROS production, and markedly increases the expression of apoptosis (Apoptosis) related proteins (DR5, Fas, caspase-8, Cyt-c, caspase-3, cleaved-PARP1, Bax). FMP exhibits antiproliferative activity against breast cancer.

KT-253 is a p53 stabilizer and a PROTAC degrader of MDM2 (DC50=0.4 nM). It inhibits the proliferation of cancer cells RS4;11 with an IC50 of 0.3 nM, induces cell cycle arrest in the G2 M phase, and triggers apoptosis. In mouse models, KT-253 demonstrates antitumor activity. (Pink: ligand for target protein MDM2 ligand 4; Black: linker; Blue: ligand for E3 ligase cereblon)

MI-888 (TFA) is an orally active inhibitor of the MDM2-p53 interaction with a Ki of 0.44 nM. It can induce rapid, complete, and durable tumor regression in xenograft mouse models.

TCF4 β-catenin-IN-1 (Compound 8b) is an inhibitor of TCF4 β-catenin that induces apoptosis. This compound enhances the expression of p53, caspase-3, caspase-8, caspase-9, and Bax proteins, while reducing Bcl-2 protein levels. TCF4 β-catenin-IN-1 also inhibits CYP3A4, CYP1A2, and CYP2C19, demonstrating significant cytotoxic activity in cancer cells.

PROTAC LZK-IN-1 (Compound 21A) is a PROTAC molecule that targets the degradation of LZK (leucine zipper kinase, encoded by MAP3K13). At a concentration of 10 μM, PROTAC LZK-IN-1 facilitates the degradation of LZK and inhibits the expression of p53 and c-MYC, leading to reduced viability of global head and neck squamous cell carcinoma (HNSCC) cell lines. This compound is applicable in anticancer research.

SIRT-IN-7 (Compound 7ba) is a SIRT inhibitor. It effectively suppresses the expression of SIRT1, SIRT2, and SIRT3, leading to increased acetylation and activation of p53. Additionally, SIRT-IN-7 inhibits the proliferation of breast cancer cells and induces apoptosis and autophagy, demonstrating antitumor activity.

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

Minocycline hydrochloride (Minocycline HCl) is a tetracycline antibiotic with excellent absorption and tissue penetration that is used for several bacterial infections as well as treatment of acne. Minocycline hydrochloride can cause both an acute hepatitis-like syndrome occurring within 1 to 3 months of starting therapy or a more insidious chronic hepatitis with autoimmune features typically after long-term treatment.

Nutlin-3a is the active enantiomer of Nutlin-3, an MDM2 antagonist that inhibits MDM2-p53 interaction (Ki=90 nM) and activates p53. Nutlin-3a binds preferentially to the p53-binding pocket of MDM2, leading to stabilization of p53 and activation of the p53 pathway. Nutlin-3a has antitumor activity.

Pifithrin-μ (NSC-303580) is an inhibitor of p53 and HSP70, with neuroprotective and antitumor activity.

Pifithrin-α hydrobromide (Pifithrin-α hydrobromide) is a p53 inhibitor, inhibiting p53-dependent transactivation of p53-responsive genes.

Amifostine (Ethyol) anhydrous is a cytoprotective agent, acts as a free radical scavenging activity.

CBL0137 hydrochloride (Curaxin-137 hydrochloride) is an inhibitor of the histone chaperone FACT, which also activates p53 and inhibits NF-κB with EC50 values ​​of 0.37 and 0.47 μM, respectively. CBL0137 hydrochloride functionally inactivates the complex that promotes chromatin transcription (FACT), thereby driving effects on p53 and NF-κB and promoting cancer cell death, and when used in combination with cisplatin, CBL0137 hydrochloride has potent anticancer activity against SCLC.

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

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.

Nutlin-3 is an MDM2 antagonist that inhibits MDM2-p53 interaction (Ki=90 nM) and activates p53. Nutlin-3 binds preferentially to the p53-binding pocket of MDM2, leading to stabilization of p53 and activation of the p53 pathway. Nutlin-3 has antitumor activity.