MDM-2/p53

Related Products

The p53 tumor suppressor is a principal mediator of growth arrest, senescence, and apoptosis in response to a broad array of cellular damage. p53 is a short-lived protein that is maintained at low, often undetectable, levels in normal cells. Under stress conditions, the p53 protein accumulates in the cell, binds in its tetrameric form to p53-response elements and induces the transcription of various genes.

MDM-2 is transcriptionally activated by p53 and MDM-2, in turn, inhibits p53 activity in several ways. MDM-2 binds to the p53 transactivation domain and thereby inhibits p53-mediated transactivation. MDM-2 also contains a signal sequence that is similar to the nuclear export signal of various viral proteins and, after binding to p53, it induces its nuclear export. As p53 is a transcription factor, it needs to be in the nucleus to be able to access the DNA; its transport to the cytoplasm by MDM-2 prevents this. Finally, MDM-2 is a ubiquitin ligase, so is able to target p53 for degradation by the proteasome.

In many tumors p53 is inactivated by the overexpression of the negative regulators MDM2 and MDM4 or by the loss of activity of the MDM2 inhibitor ARF. The pathway can be reactivated in these tumors by small molecules that inhibit the interaction of MDM2 and/or MDM4 with p53. Such molecules are now in clinical trials.

MDM-2/p53 Related Products (373)
Antibodies (18)
MDM-2/p53 Signaling Pathway

By Effects:	Controls (4) Ligand (1) Inhibitors (74) Agonist (1) Degraders (5) Antagonists (2) Activators (64) Modulators (11) MDM2 Inhibitors (60) p53 Activators (77) p53 Inhibitors (11) Inducers (13)

Cat. No.	Product Name	Effect	Purity	Chemical Structure

HY-170591

p53 Activator 14	p53 Activator
p53 Activator 14 (Compound 7A) is a derivative of Neratinib (HY-32721), that induces DNA damage, activates p53, and inhibits the proliferation of multi cancer cells (IC₅₀=7.21 μM for HCT116 cell). p53 Activator 14 inhibits the adhesion, migration and invasion of HCT116, arrests the cell cycle, and induces apoptosis. p53 Activator 14 inhibits angiogenesis and exhibits antitumor efficacy in chick chorioallantoic membrane (CAM) model.

HY-N10502

Colletofragarone A2	Inhibitor
Colletofragarone A2 can be be isolated from the fungus Colletotrichum sp. (13S020). Colletofragarone A2 inhibits mutant p53 and HSP90 with anti-cancer activity. Colletofragarone A2 promotes degradation and aggregation of mutant p53 and suppressing tumor growth in vivo.

HY-125660

Leucettamol A	Activator
Leucettamol A is an inhibitor of Ubc13 (ubiquitin E2 enzyme)-Uev1A interaction, with an IC₅₀ of 50 μg/mL. Leucettamol A can potentially activate the expression of cancer suppressor p53 and is a precursor of anticancer agents. Leucettamol A can be isolated from a marine sponge, Leucetta aff. Microrhaphis.

HY-118912

BMH-9	Activator
BMH-9 (Compound Z54) is a modulator for nuclear receptor subfamily 2, group F, member 6 (NR2F6) (also known as nuclear orphan receptor Ear2). BMH-9 is an activator for p53 signaling pathway through interaction with DNA. BMH-9 inhibits proliferation of human cancer cells, exhibits antitumor efficacy in NOD-SCID mouse models.

HY-144104

NSC90616	Activator
NSC90616 is a mutant p53 rescue compound.

HY-W287494

Antitumor agent-202	Modulator
Antitumor agent-202 is a stabilizer of the p53 Y220C mutant. It exhibits a selective inhibitory effect on the proliferation of tumor cells carrying the p53 Y220C mutation and can be applied to the research of cancers associated with the p53 Y220C mutation.

HY-124072

HL001	Modulator
HL001 is an orally active small molecule inhibitor of Cyclophilin A (CypA) and a receptor antagonist of Lysophosphatidic acid 1 (LPA1). HL001 induces cell cycle arrest and apoptosis of tumor cells by p53. HL001 stabilizes p53 by down-regulating G3BP1, inducing reactive oxygen species and DNA damage. HL001 disrupts the interaction between MDM2 and p53-72R in a CypA dependent manner. HL001 has antitumor activity. HL001 can also be used to study pulmonary fibrosis.

HY-12579

RO 2468	Inhibitor
RO 2468 is a potent, orally active and selective p53-MDM2 inhibitor. RO 2468 has anti-proliferative active. RO 2468 suppresses c growth in SJSA1 osteosarcoma models without obvious toxicity.

HY-149250

MDMX/MDM2-IN-2	Inhibitor
MDMX/MDM2-IN-2 is a potent p53-MDM2/MDMX dual inhibitors with K_is of 0.23 μM and 2.45 μM for MDM2 and MDMX, respectively. MDMX/MDM2-IN-2 inhibits the binding of p53 and MDM2 proteins. MDMX/MDM2-IN-2 restores the function of p53 and enables cell cycle arrest and apoptosis. MDMX/MDM2-IN-2 inhibits cell migration and invasion. MDMX/MDM2-IN-2 has antitumor activity.

HY-W708917

Lumichrome-d₈
Lumichrome-d₈ is the deuterium labeled Lumichrome (HY-115385). Lumichrome, a photodegradation product of Riboflavin, is an endogenous compound in humans. Lumichrome inhibits human lung cancer cell growth and induces apoptosis via a p53-dependent mechanism. Lumichrom is the inhibitor for AKT/β-catenin signaling pathway.

HY-N0068R

Solasodine (Standard)	MDM2 Inhibitor
Solasodine (Standard) is the analytical standard of Solasodine. This product is intended for research and analytical applications. Solasodine (Purapuridine) is a steroidal alkaloid that occurs in plants of the Solanaceae family. Solasodine has neuroprotective, antifungal, hypotensive, anticancer, antiatherosclerotic, antiandrogenic and anti-inflammatory activities.

HY-128843

PROTAC MDM2 Degrader-4	MDM2 Inhibitor
PROTAC MDM2 Degrader-4 is a MDM2 degrader based on PROTAC technology. PROTAC MDM2 Degrader-4 composes of a potent MDM2 inhibitor, linker, and the MDM2 ligand for E3 ubiquitin ligase.

HY-174301

USP7-IN-18	Activator
USP7-IN-18 is a naphthalene derivative. USP7-IN-18 is a selective USP7 inhibitor (IC₅₀ : 130.9 nM), with no or very weak inhibition of the other 8 DUBs including USP47. USP7-IN-18 specifically binds to the catalytic domain of USP7, blocking its deubiquitinase activity. USP7-IN-18 causes degradation of the oncogenic proteins MDM2 and DNMT1, and also degrades the novel target PCLAF. USP7-IN-18 activates the p53-p21 pathway. USP7-IN-18 exerts anti-tumor effects in colon cancer animal models and reshapes the tumor immune microenvironment. USP7-IN-18 achieves both direct cytotoxic and immune-synergistic anti-tumor actions.

HY-168606A

p53-MDM2-IN-7 hydrochloride	Inhibitor
p53-MDM2-IN-7 (compound 6d) (hydrochloride) is a p53-MDM2 inhibitor. p53-MDM2-IN-7 has an IC₅₀ value of 8.13 μM against A549 cells. p53-MDM2-IN-7 can be used in anti-cancer research.

HY-159606

MS182	Inhibitor
MS182 (compound 11) is an acetylation targeting chimera (AceTAC) designed based on p53^Y220C stabilizer and targeting p53^Y220C. MS182 is composed of p53^Y220C and p300/CBP binders, respectively, coupled by a linker. MS182 forms a ternary complex with p300/CBP acetyltransferase and p53^Y220C in a time- and concentration-dependent manner, effectively acetylating lysine at position 382 of p53^Y220C (ACE₅₀: 1.52 μM). MS182 also exhibited considerable bioavailability in mice, with GI₅₀ values of 2.16 μM and 1.83 μM for BxPC3 (p53^Y220C/-) and NUGC (p53^Y220C/+), respectively.

HY-P5343

p53 CBS
p53 CBS (p53 Consensus binding sequence) is a biological active peptide. (p53 consensus DNA binding site)

HY-145907

p53-HDM2-IN-1	Inhibitor
p53-HDM2-IN-1 is a potent inhibitor of p53-HDM2 protein-protein interaction, with an IC₅₀ of 0.103 μM. p53-HDM2-IN-1 can be used for the research of cancer.

HY-133760

MI-888	Inhibitor
MI-888 is an orally active MDM2 inhibitor with a K_i of 0.44 nM. MI-888 can inhibit the MDM2-p53 interaction. MI-888 has favorable pharmacokinetic properties and anti-tumor activity.

HY-W750535

Triglycidyl Isocyanurate-d₁₅
Triglycidyl Isocyanurate-d₁₅ is the deuterium labeled Triglycidyl isocyanurate (HY-W011434). Triglycidyl isocyanurate (TGIC; Teroxirone) is a triazene triepoxide with antiangiogenic and antineoplastic activities. Triglycidyl isocyanurate inhibits the growth of non-small-cell-lung cancer cells via p53 activation. Triglycidyl isocyanurate induces cell apoptosis. Triglycidyl isocyanurate can be used for cancer research.

HY-123950

MMRi64	Inhibitor	≥98.0%
MMRi64 disrupts Mdm2-MdmX interactions. MMRi64 downregulates Mdm2 and MdmX in leukemia cells. MMRi64 induces p53 accumulation, and induces the apoptotic arm of the p53 pathway in leukemia/lymphoma cells. MMRi64 can be used for cancer research.

Hypoxia rNTP
Depletion DNA Damage SV40, HPV or
Adenovirus Spindle
Damage Oncogene
Activation PI3K GFRs:
IGF1R, ERBB Family,
etc. c-Abl ATM ATR CDK-Cyclin JNK p38 Chk1 Chk2 RB RB E2F1 E2F1 Akt SV40, HPV or
Adenovirus p53 p53 Myc ARF Calpains p53 p53 MDM-2 MDM-4 DAXX USP7 Proteasome p53 p53 p53 p53 HATs HDAC p21 Cyclin D CDK4/6 Cyclin E CDK2 14-3-3-σ Reprimo Gadd45 Cyclin B Cdc2 B99 Fas Cell cycle arrest PIDD DR5 Caspase 8 Bid Apaf-1 CytC Caspase 3 Bax Noxa PUMA p53AIP Apoptosis Caspase 9 PIGs Scotin PERP PAG608 Siah IGF-BP3 IGF PAI BAI-1 KAI GD-AiF TSP1 Maspin p53R2 Gadd45 p48 Sestrins DND repair
and
damage prevention PTEN TSC2 IGF-BP3 Inhibition
of
IGF-1/mTOR
pathway TSAP6 MDM-2 Cop-1 PIRH-2 Cyclin G Siah-1 Wip1 ΔNp73

Download MDM-2/p53 Signaling Pathway Map.

p53 is at the centre of biological interactions that translates stress signals into cell cycle arrest or apoptosis. Upstream signaling to p53 increases its level and activates its function as a transcription factor in response to a wide variety of stresses, whereas downstream components execute the appropriate cellular response.

Cell Stress: p53 induction by acute DNA damage begins when DNA double-strand breaks trigger activation of ATM, a kinase that phosphorylates the CHK2 kinase, or when stalled or collapsed DNA replication forks recruit ATR, which phosphorylates CHK1. p53 is a substrate for both the ATM and ATR kinases, as well as for CHK1 and CHK2, which coordinately phosphorylate p53 to promote its stabilization. These phosphorylation events are important for p53 stabilization, as some of the modifications disrupt the interaction between p53 and its negative regulators MDM2 and MDM4. MDM2 and MDM4 bind to the transcriptional activation domains of p53, thereby inhibiting p53 transactivation function, and MDM2 has additional activity as an E3 ubiquitin ligase that causes proteasome-mediated degradation of p53. Phosphorylation also allows the interaction of p53 with transcriptional cofactors, which is ultimately important for activation of target genes and for responses such as cell cycle arrest, DNA repair, apoptosis and senescence. Non-receptor tyrosine kinase c-Abl can also be activated by DNA damage. Then the JNK/p38 is activated and leads to p53 activation^[1][2].

Oncogenic signaling: The response to oncogene activation depends on the binding of ARF to MDM2. ARF is normally expressed at low levels in cells. Inappropriately increased E2F or Myc signals, stemming from oncogene activation, leads to the increased expression of ARF, which inhibits MDM2 by blocking its E3 ubiquitin ligase activity, uncoupling the p53-MDM2 interaction, thereby segregating it from nucleoplasmic p53^[3].

The PI3K-Akt pathway activates MDM2 and increases the ubiquitination of p53.

Reference:
[1]. Chène P, et al. Inhibiting the p53-MDM2 interaction: an important target for cancer therapy. Nat Rev Cancer. 2003 Feb;3(2):102-9.
[2]. Brown CJ, et al. Awakening guardian angels: drugging the p53 pathway. Nat Rev Cancer. 2009 Dec;9(12):862-73.
[3]. Polager S, et al. p53 and E2f: partners in life and death. Nat Rev Cancer. 2009 Oct;9(10):738-48. doi: 10.1038/nrc2718.

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MDM-2/p53

MDM-2/p53

MDM-2/p53 Related Products (373)

Antibodies (18)

MDM-2/p53 Signaling Pathway

MDM-2/p53 Related Products (373):