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 (551)
Antibodies (17)
MDM-2/p53 Signaling Pathway

By Effects:	Inhibitors (100) Agonists (8) Degraders (6) Controls (6) Ligands (6) Antagonists (4) Activators (126) Modulators (22) MDM2 Inhibitors (64) p53 Activators (101) p53 Inhibitors (15) Inducers (17)

Cat. No.	Product Name	Effect	Purity	Chemical Structure

HY-18343

CP-31398	p53 Activator
CP-31398 can stabilize the active conformation of p53 and promote p53 activity in cancer cells with either mutant or wild-type p53. In addition, CP-31398 can upregulate p53 target genes, such as p21WAF1/Cip1 and KILLER/DR5. CP-31398 exerts an inhibitory effect on tumor growth.

HY-161874

RPS6-IN-1	Inducer
RPS6-IN-1 (Compound 22o) inhibits cell metastasis, induces cell apoptosis (increases the expression of Bax, p53, cleaved-caspase 3, and cleaved-PARP). RPS6-IN-1 decreases mitochondrial membrane potential. RPS6-IN-1 activates autophagy through the PI3K-Akt-mTOR signaling pathway, damages intracellular mitochondria and lysosomes, and cause ER stress. RPS6-IN-1 inhibits RPS6 phosphorylation. RPS6-IN-1 is an anticancer agent with low systemic toxicity.

HY-12296S

Navtemadlin-d₇	MDM2 Inhibitor
Navtemadlin-d₇ is the deuterium labeled Navtemadlin. Navtemadlin (AMG 232) is a potent, selective and orally available inhibitor of p53-MDM2 interaction, with an IC₅₀ of 0.6 nM. Navtemadlin binds to MDM2 with a Kd of 0.045 nM.

HY-175608

EGFR-IN-171	p53 Activator
EGFR-IN-171 is an EGFR inhibitor with an IC₅₀ value of 0.19 μM. EGFR-IN-171 also inhibits vascular endothelial growth factor 2 (VEGFR-2) with an IC₅₀ value of 31.65 μM. EGFR-IN-171 can induce apoptosis and G2/M phase cell cycle arrest. EGFR-IN-171 can be used for cancer research, such as liver and breast cancer.

HY-123544

RDR03871	MDM2 Inhibitor
RDR03871 (compound 2) is a potent dual MDM2/MDM4 inhibitor with IC₅₀ values of 35.4 nM and 10.4 nM for MDM2-p53 and MDM4-p53, respectively.

HY-119228

SN-28049	Activator
SN-28049 is a new DNA-binding topoisomerase II-directed antitumor agent. SN-28049 activates the p53 pathway. SN-28049 exhibits anticancer activity against colorectal cancer.

HY-16634

MI-888 TFA	Inhibitor
MI-888 (TFA) is an orally active MDM2-p53 interaction inhibitor with a K_i of 0.44 nM. MI-888 (TFA) can achieve rapid, complete, and sustained tumor regression in a xenograft mouse model of cancer.

HY-183622

UCI-1014	Activator
UCI-1014 is a mutant p53 (p53^R175H) corrector/reactivator. UCI-1014 restores the wild-type-like DNA-binding activity of p53^R175H, promotes the redistribution of the mutant protein to chromatin, and induces the expression of p53-dependent target genes. UCI-1014 inhibits the proliferation of p53^R175H-mutant cancer cells through an SLC7A11-independent mechanism. UCI-1014 can be used for research related to p53-mutant cancers.

HY-170900

SJ44236	Activator
SJ44236 is a BET PROTAC degrader with activity against BRD2, BRD3 and BRD4 (DC₅₀ = 127 pM). SJ44236 induces ubiquitination and proteasomal degradation by forming a ternary complex with BET proteins and CRBN-DDB1. SJ44236 downregulates c-Myc, upregulates p53 and reduces cancer cell viability. SJ44236 can be used for the research of leukemia and medulloblastoma.

HY-160449

p53 Activator 10	Activator
p53 Activator 10 (Example C-2) is a compound that targets the y220c mutant of p53. p53 Activator 10 activation is involved in the downstream effects of tumor suppression.

HY-149988

UNP-6457	Inhibitor
UNP-6457 is a potent active MDM2-p53 interaction inhibitor with an IC₅₀ values of 8.9 nM.

HY-N2037AS

Higenamine-d₄ hydrochloride	Activator
Higenamine-d₄ (Norcoclaurine-d₄; Demethyl-Coclaurine-d₄) hydrochloride is deuterium-labeled Higenamine (hydrochloride) (HY-N2037A).

HY-151171

MDM2/4-p53-IN-3	Inhibitor
MDM2/4-p53-IN-3 is a MDM2/4-p53 protein-protein interactions (PPIs) inhibitor (IC₅₀s: 18.5 nM for MDM2-p53, 14.8 nM for MDM4-p53). MDM2/4-p53-IN-3 can be used in the research of cancers, such as colon cancer.

HY-149024

VEGFR-2-IN-23	p53 Activator
VEGFR-2-IN-23 (compound 11b) is a potent and selective VEGFR-2 inhibitor with an IC₅₀ value of 0.34 nM. VEGFR-2-IN-23 shows antitumor activity. VEGFR-2-IN-23 induces apoptosis and cell cycle arrest at G1 phase.

HY-B0860R

Diuron (Standard)	Activator
Diuron (Standard) is the analytical standard of Diuron (HY-B0860). This product is intended for research and analytical applications. Diuron is an orally active phenylurea herbicide. Diuron inhibits photosynthesis in plants by blocking the formation of ATP and NADH. Diuron increases the production of ROS. Diuron increases expression of p53 in certain cell lines. Diuron has herbicidal activity against annual and perennial broadleaf weeds and grass weeds. Diuron promotes DMBA/BBN-induced bladder cancer. Diuron can be used in breast cancer research.

HY-132595C

Teprasiran sodium scrambled negative control
Teprasiran sodium scrambled negative control is the sequence scrambled negative control of Teprasiran sodium.

HY-175785

X15695	Agonist	98.45%
X15695 is selective and orally active estrogen receptor (ERα) degrader. X15695 is an aryl hydrocarbon receptor (AHR) ligand. X15695 enables AHR to form a complex with the ERα, promoting its proteasomal degradation. X15695 inhibits the breast cancer cells proliferation, promotes cell cycle block and induces apoptosis. X15695 can be used for the study of breast cancer.

HY-165381

ZMC2
ZMC2 is a thiosemicarbazone-class metal ion chelator and zinc ionophore with a human mutant p53^R175H binding K_a of 27.4 nM.ZMC2 binds Fe, Cu, Mn, Zn, and other transition metals.ZMC2 facilitates zinc transport across membranes.ZMC2 restores zinc binding to zinc-deficient p53 mutants, restoring wild-type structure and function, including site-specific DNA binding.ZMC2 generates reactive oxygen species (ROS).ZMC2 can be used for the research of cancer.

HY-163275

MDM2-IN-24	Inhibitor
MDM2-IN-24 (compound A3f) exhibits MDM2-inhibiting and MDMX-activating properties in triple-negative breast cancer (TNBC) cells, with apoptotic and anti-proliferative activities.

HY-108640

HLI373	MDM2 Inhibitor
HLI373 is an efficacious Hdm2 inhibitor. HLI373 inhibits the ubiquitin ligase activity of Hdm2. HLI373 is effective in inducing apoptosis of several tumor cells that are sensitive to DNA-damaging agents. Antimalarial activity.

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 (551)

Antibodies (17)

MDM-2/p53 Signaling Pathway

MDM-2/p53 Related Products (551):