p53-dependent

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.

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.

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.

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.

1. Protosappanin B (Q-100961) significantly increases cell viability, inhibits cell apoptosis and up-regulates the expression of growth-associated protein 43. 2. Protosappanin B induces the degradation of p53 protein, via activation of a MDM2-dependent ubiquitination process.

Pifithrin-β hydrobromide (Cyclic PFT-α) is an inhibitor of p53; reversibly blocks p53-dependent transcriptional activation and apoptosis. Protects against neuronal death in models of stroke and neurodegenerative disorders. Active in vivo; protects mice from the side-effects of Y therapy associated with p53 induction. Supresses self-renewal of embryonic stem cells. Also aryl hydrocarbon receptor (AHR) agonist, causes upregulation of AHR target gene CYP1A1 (EC50 = 1.1 μM).

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

1. Atractylenolide II (2-Atractylenolide) has antimelanoma effect by inhibiting STAT3 signalling. 2. Atractylenolide II has cytotoxic apoptotic effects may via p38 activation , ERK and Akt inactivation, p53 dependent.

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).

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

1. Vitexin has antinociceptive and antispasmodic activities. 2. Vitexin exhibits a prominent first-pass effect. 3. Vitexin has antioxidant, antimyeloperoxidase, and α-glucosidase inhibitory activities. 4. Vitexin can either inhibit or induce activities of

BML-259 is an inhibitor of CDK5 and CDK2 with IC50s of 64 and 98 nM, respectively. BML-259 can be used in studies about the treatment of cancer and neurodegenerative diseases.

Cambinol (SIRT1/2 Inhibitor IV) is a cell-permeable b-naphthol compound that inhibits the NAD-dependent deacetylase activity of SIRT1/2 (IC50: 56/59 μM, respectively) in a substrate-, but not NAD-, competitive manner. Cambinol inhibits SIRT5 deacetylase activity only at much higher concentrations (IC50 >300 μM) and no inhibitory for the class I and II HDACs. In BCL6-expressing Burkitt lymphoma cell lines, Cambinol-induced apoptosis has been attributed to the hyperacetylation of p53 and BCL6.Cambinol is a potent brain penetrant neutral sphingomyelinase (N-SMase) inhibitor (exosome inhibitor)

MG-115 (Z-LL-Nva-CHO) is a potent and reversible inhibitor of proteasome , with K i s of 21 nM and 35 nM for 20S and 26S proteasome, respectively. MG-115 specifically inhibit the chymotrypsin-like activity of the proteasome, induces p53-dependent apoptosis [1] [2] [3].

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.

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.

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.

Cjoc42 is an inhibitor of gankyrin, an ankyrin-repeat oncoprotein whose overexpression has been implicated in the development of many cancer types. cjoc42 prevents the decrease in p53 protein levels normally associated with high amounts of gankyrin, and it restores p53-dependent transcription and sensitivity to DNA damage

Tumor protein p53 binding protein (53BP1) has been identified in a yeast two-hybrid screen as a protein that interacts with the central DNA–binding domain of p532. Similar to breast cancer susceptibility gene 13, 4 (BRCA1; 53BP1 enhances p53-dependent tra

RUNX-IN-1, also known as Compound Conjugate 1, covalently attaches to RUNX-binding sequences, thereby preventing RUNX proteins from associating with their specific targets. This compound triggers p53-dependent apoptosis and suppresses the proliferation of cancer cells. Furthermore, RUNX-IN-1 has demonstrated efficacy in impeding tumor progression in PANC-1 xenograft mice [1].

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

Teprasiran (QPI-1002) is an RNA-based compound that transiently suppresses p53-dependent apoptosis, a process involved in the development of acute kidney injury (AKI).

HBX 41108 (HBX-41108) is a non-competitive, reversible inhibitor of USP7 with an IC50 of 424nM. HBX 41108 inhibited deubiquitination of p53 mediated by USP7 in a dose-dependent manner with an IC50 of 0.8μM.

GPR, a tripeptide, shows promise in Alzheimer's disease (AD) research by protecting cultured rat hippocampal neurons from amyloid-beta (Aβ)-induced death through the inhibition of caspase-3/p53-dependent apoptosis.

NSC-279287 is a novel Inhibitor of the p53-mdm2 Interaction, Activating p53-Dependent Transcription in mdm2-Overexpressing Cells.

CDK1-IN-7 is a potent inhibitor of CDK1 with an IC50 value of 161.2 nM for CDK1/CycB. CDK1-IN-7 induces apoptosis in a p53-dependent manner via the apoptosis-intrinsic pathway. CDK1-IN-7 selectively acts on tumour tissue and has potential anti-proliferative effects. CDK1-IN-7 is a potential CDK1-IN-7 is a potential targeted anti-tumour agent.

Eurycomanone (Pasakbumin A) is cytotoxic on HepG2 cells by inducing apoptosis through the up-regulation of p53 and Bax, and down-regulation of Bcl-2.Eurycomanone has anti-cancer activity, inhibits A549 lung cancer cell proliferation in a dose-dependent manner at concentrations ranging from 5 to 20 μg ml.

Coenzyme Q10 is a component of the electron transport chain and participates in aerobic cellular respiration, generating energy in the form of ATP. In its reduced form, it acts as an antioxidant. Coenzyme Q2 is a precursor of coenzyme Q10 that has 2, rather than 10, isoprenoid units on the ubiquinone base. It can act as an electron acceptor for bacterial Complex I. In mammalian cells, exogenous coenzyme Q2 prevents the production of reactive oxygen species associated with Complex I activity. Forms of coenzyme Q with shorter isoprenoid chains, including coenzyme Q2, induce p53-dependent apoptosis in human B-cell acute lymphoblastoid leukemia BALL-1 cells.

XL177A is a selective irreversible USP7 inhibitor(IC50 : 0.34 nM). XL177A elicits cancer cell killing through a p53-dependent mechanism.

RUNX-IN-2 (Compound Conjugate 3) covalently attaches to RUNX-binding sequences, preventing RUNX proteins from associating with their targets, thereby inhibiting cancer cell proliferation and inducing p53-dependent apoptosis. Furthermore, RUNX-IN-2 suppresses tumor development in PANC-1 xenograft mice and demonstrates notable alkylation efficiency and specificity [1].

YW3-56 is an inhibitor of protein arginine deiminase 2 (PAD2) and PAD4 (IC50s = 0.5-1 and 1-5 μM, respectively).1It inhibits the growth of U2OS osteosarcoma cells (IC50= ~2.5 μM) in a p53-dependent mannerviainduction of SESN2 and subsequent inhibition of mTORC1. YW3-56 (10 mg/kg) reduces tumor growth in an S-180 murine sarcoma tumor model. It also inhibits tumor growth in the 1883 MDA-MB-231 breast cancer bone metastasis mouse xenograft model.2 1.Wang, Y., Li, P., Wang, S., et al.Anticancer peptidylarginine deiminase (PAD) inhibitors regulate the autophagy flux and the mammalian target of rapamycin complex 1 activityThe Journal of Biological Chemisty287(31)25941-25952(2012) 2.Wang, S., Chen, X.A., Hu, J., et al.ATF4 gene network mediates cellular response to the anticancer PAD inhibitor YW3-56 in triple-negative breast cancer cellsMol. Cancer Ther.14(4)877-888(2015)

Ivaltinostat (CG-200745) formic is an orally active pan-HDAC inhibitor with an isohydroxamic acid component that binds zinc at the bottom of the catalytic pocket. Ivaltinostat formic inhibits the deacetylation of histone H3 and tubulin, promotes p53 accumulation, induces p53-dependent transactivation, and enhances MDM2 and p21 (Waf1 Cip1) protein expression. It increases the sensitivity of Gemcitabine-resistant cells to Gemcitabine and 5-Fluorouracil (5-FU), induces apoptosis, and has antitumor effects.

SIRT2-IN-11 (AEM1) is a selective inhibitor of SIRT2 with an inhibitory concentration (IC50) of 18.5 μM. It induces apoptosis in a p53-dependent manner, activates the expression of CDKN1A, PUMA, and NOXA, and enhances the acetylation of p53. This compound is utilized in the study of p53-associated cancers.

Olomoucine II is an inhibitor of cyclin-dependent kinases (CDKs; IC50s = 7.6, 0.1, 19.8, 0.45, and 0.06 μM for Cdk1, -2, -4, -7, and -9, respectively).1It is selective for CDKs over 10 additional kinases (IC50s = >100 μM for all) but does inhibit ERK2 (IC50= 32 μM) and the ATP-binding cassette transporter B1 (ABCB1; IC50= 6.4 μM).1,2Olomoucine II inhibits proliferation of a variety of cancer cells, including those expressing wild-type p53 or mutant p53 (mean IC50s = 7.4 and 10.1 μM, respectively), and it acts synergistically with daunorubicin to inhibit proliferation of HCT-8 cells that endogenously express ABCB1. Olomoucine also inhibits replication of herpes simplex virus 1 (HSV-1), HSV-2, vaccinia virus, human adenovirus type 4 (Ad4), and human CMV (IC50s = 5, 4.7, 3.8, 2.4, and 3.2 μM, respectively) but not measles virus or influenza virus (IC50s = >20 μM for both).3

ABL-L is able to induce apoptosis in human laryngeal cancer cells using a p53-dependent pathway.

XK489 is a synthetic quinoxaline phenoxypropionic acid derivative with proapoptotic and antiproliferative activities. R(+)XK469 selectively inhibits topoisomerase II-beta, blocks activation of MEK/MAPK signaling kinases, stimulates caspases, and upregulates p53-dependent proteins, including cyclins A and B1, thereby arresting cancer cells in the G2/M phase of the cell cycle. Both R(+) and S(-) isomers of this agent are cytotoxic, although the R-isomer is more potent.

Eriocalyxin B induces apoptosis and cell cycle arrest in pancreatic adenocarcinoma cells through caspase- and p53-dependent pathways, should be considered a candidate for pancreatic cancer treatment; it is a specific inhibitor of STAT3, it directly target

K34c is a potent and selective α5β1 integrin inhibitor (IC50 = 3.1 nM) that inhibits cell survival and migration, p53-dependent senescence induced by Temozolomide or Ellipticine, and promotes apoptosis in U87MG cells. Additionally, K34c prevents TGFβ-induced infiltration [in vivo] and reduces cell adhesion on fibronectin.

Sirtuins (SIRTs) represent a distinct class of trichostatin A-insensitive lysyl-deacetylases (class III HDACs). Human SIRT1 is the homolog of yeast silent information regulator 2 (Sir2) and has been shown to regulate the activity of the p53 tumor suppressor and inhibit apoptosis. Small molecule activators of SIRT1, such as resveratrol, extend lifespan in yeast and C. elegans in a manner that resembles caloric restriction. CAY10591 has been identified as an activator of the enzyme SIRT1. This compound increases fluorescence by 233% in a SIRT1 activity assay. [Activator activity was defined as the percentage of signal increase relative to signal window in the following formula: 100 x (Sample - Signallow)/(Signalhigh - Signallow)]. CAY10591 suppresses TNF-α in a dose-dependent manner. In THP-1 cells, TNF-α levels decreased from 325 pg/ml (control) to 104 and 53 pg/ml with 20 and 60 µM CAY10591, respectively. This activator also has a significant dose-dependent effect on fat mobilization in differentiated adipocytes, which would indicate the potential of SIRT1 activators for anti-obesity or anti-diabetic purposes.

Amifostine thiol (WR-1065) is a radioprotectant that protects DNA from fast neutron-induced strand breaks.Amifostine thiol ameliorates (P<0.001) 6-OHDA-induced stiffness in a dose-dependent manner and activates p53 through a JNK-dependent signaling pathway.

MEL24, an Mdm2 E3 ligase inhibitor, diminishes cell viability and enhances sensitivity to DNA-damaging agents in a p53-dependent manner, suggesting its potential for in vitro antitumor research [1].

XL-188 is a highly potent and selective inhibitor of USP7. XL188 inhibited USP7 catalytic domain and full-length enzyme with IC50 values of 193 and 90 nM, respectively. XL188 Promotes USP7-Dependent Loss of HDM2 and Increase of p53 and p21. XL188 represents one of only a small set of mammalian DUB inhibitors with low nanomolar potency and a high degree of selectivity relative to other DUBs

CC260, a selective inhibitor for PI5P4Kα and PI5P4Kβ with Kis of 40 nM and 30 nM respectively, exhibits minimal to no inhibition against other protein kinases like Plk1 and RSK2. It is applicable in the research of cell energy metabolism, diabetes, and cancer[1].

Cadein1, an isoquinolinium derivative, induces G2/M phase delay and caspase-dependent apoptosis in cancer cells lacking functional p53.

1. Isoliquiritin (Neoisoliquritin) has antitussive effects. 2. Isoliquiritin has antidepressant-like effects. 3. Isoliquiritin, liquiritin and isoliquirigenin inhibits the p53-dependent pathway and shows crosstalk between Akt activities.