p53-dependent

Naphthazarin (5,8-Dihydroxy-1,4-naphthoquinone) is effective by various cellular mechanisms including oxidative stress, activation of mitochondrial apoptosis-inducing factor (AIF), depolymerization of microtubules, interference with lysosomal function and p53-dependent p21 activation. It triggers apoptosis and has anti-tumor effects

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

AK301 is a potent and selective inhibitor of tubulin polymerization and an effective sensitizer of cancer cells to apoptotic ligands (EC50 < 200 nM). Colon cancer cells arrested in mitosis with AK301 readily underwent a p53-dependent apoptosis following compound withdrawal and arrest release.

CT-1 is a DNA minor groove ligand and causes p53-dependent breast cancer cell apoptosis.

Pentamidine dimesylate is an inhibitor of calcium-dependent complex formation with p53 [(Ca)S100B-p53) in malignant melanoma (MM). Pentamidine dimesylate restores p53 tumor suppressor activity in vivo.

Sarmustine (SarCNU) is an alkylating agent with anticancer activity that inhibits the growth of prostate cancer cells via p53-dependent and p53-independent pathways.Sarmustine mediates the selection of P140K methylguanine-DNA-methyltransferase-transduced human CD34(+) cells in vitro.

Vesnarinone (Arkin) (INN) is a mixed phosphodiesterase 3 inhibitor and ion-channel modifier that has modest, dose-dependent, positive inotropic activity, but minimal negative chronotropic activity. It also suppresses cell proliferation and induces apoptosis by inducing the expression of p21, an inhibitor of cyclin-dependent kinase activity in p53-mediated cell cycle arrest.

P53R3 is a potent reactivator of p53, effectively restoring sequence-specific DNA binding to several p53 hot spot mutants, namely p53 R175H, p53 R248W, and p53 R273H. This compound exhibits p53-dependent antiproliferative effects with significantly higher specificity compared to PRIMA-1 and promotes the recruitment of both wild-type p53 and p53 M237I to various target gene promoters. Additionally, P53R3 markedly increases the mRNA, total protein, and cell surface expression of death receptor 5 (DR5), demonstrating its utility in cancer research.

Lumichrome is an endogenous compound in humans, produced by photodegradation of riboflavin. It utilizes a p53-dependent mechanism to inhibit growth and induce apoptosis in human lung cancer cells.

Rubone (2'-Hydroxy-2,4,4',5,6'-pentamethoxychalcone), a natural product and a modulator of miR-34a (microRNA-34), upregulates miR-34a expression in a p53-dependent manner, which in turn downregulates the expression of downstream targets Bcl-2, cyclin-D1, CDK6, SIRT1, and FOXP1, thereby inhibiting tumor growth and reversal of hepatocellular carcinoma (HCC) and chemoresistance in prostate cancer.

6-Dehydrogingerdione sensitizes human hepatoblastoma Hep G2 cells to TRAIL-induced apoptosis via a reactive oxygen species-mediated mechanism that enhances DR5 expression, up-regulates Ser-15 phosphorylation, and triggers nuclear translocation of p53. Abrogation of p53 using small interfering RNA markedly reduces 6-Dehydrogingerdione-induced DR5 and diminishes TRAIL responsiveness. ROS generation accompanies DR5 activation, and pretreatment with N-acetyl-L-cysteine significantly attenuates these apoptotic responses, confirming 6-Dehydrogingerdione acts through p53-dependent and oxidative stress-mediated apoptotic pathways.

Amifostine thiol dihydrochloride (WR 1065) can activate p53 through a JNK-dependent signaling pathway. It also protects normal tissues from the toxic effects of certain cancer drugs.

Recilisib, also known as ON 01210.Na, is a radioprotectant, which modifys cell cycle distribution patterns in cancer cells subjected to radiation therapy, and it has been identified as a potential candidate for radiation protection studies. It appears tha

Alrizomadlin is an orally active MDM2 inhibitor. APG-115 shows significant dose-dependent inhibitory effects on TP53wt AML cell lines. The IC50 values ​​are 26.8 nM for MOLM-13 cells and 165.9 nM for MV-4-11 cells. , OCI-AML-3 cells 315.6 nM. Alrizomadlin blocks the interaction of MDM2 and p53 and induces cell cycle arrest and apoptosis in a p53-dependent manner.

Inauhzin (INZ)(INZ) is a novel small molecule that effectively reactivates p53 by inhibiting SIRT1 activity, promotes p53-dependent apoptosis of human Y cells without causing apparently genotoxic stress(IC50=3 uM, in A549 cell).

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/+).

Gallium 8-Hydroxyquinolinate is an inducer of apoptosis that initiates both p53-dependent and independent cell death in cancer cells through the induction of Ca2+ signaling transduction. In addition to its apoptotic properties, this compound's nanostructures exhibit excellent optical performance, making it suitable for use in tumor research.

TLBC, a borane-chalcone derivative, exhibits dose-dependent inhibitory effects across various glioma cell lines with IC50 values ranging from 5.5 to 25.5 μM. TLBC induces apoptosis independently of alterations in the tumor suppressor factor p53.

MAPK-IN-3 (Compound 4a) is an antiproliferative agent demonstrating significant inhibitory effects on KYSE 30, HCT 116, and HGC 27 cell lines, with IC50 values of 0.57 μM, 3.27 μM, and 2.28 μM, respectively. This compound arrests the cell cycle via a p53-dependent mechanism and induces apoptosis through a p53-independent pathway. It reduces the expression of cell cycle-related proteins, such as Cyclin D1 and Cyclin B1, while increasing pro-apoptotic proteins like cleaved PARP, cleaved caspase-7, and cleaved caspase-9. MAPK-IN-3 also decreases anti-apoptotic proteins such as Bcl-2, elevates ROS levels in KYSE 30 cells, and enhances the expression of ROS-related MAPK pathway members, including p-ERK, p-p38, and p-JNK.

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.

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.

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.

DEG-35 is a CRBN-dependent bifunctional degrader targeting IKZF2 and CK1α, with DC50 values of 1.4 nM and 4.4 nM for CK1α and IKZF2, respectively. It activates the p53 apoptotic pathway and is applicable for research related to acute myeloid leukemia (AML).

p53 Stabilizer 2 (Compound 17a16) is a p53 stabilizing agent. It can induce S-phase arrest and apoptosis in both p53-functional and p53-deficient cancer cells. Additionally, p53 Stabilizer 2 triggers mitochondrial stress and activates two immune checkpoint pathways: NA-PKcs dependent p53 stabilization and the ATR-Chk1 axis activation. It also inhibits tumor growth in p53-deficient xenograft models.