mdm2

MDMX/MDM2-IN-2 is a potent dual inhibitor of p53-MDM2/MDMX, demonstrating dissociation constants (Kis) of 0.23 μM for MDM2 and 2.45 μM for MDMX. It effectively disrupts the interaction between p53 and MDM2 proteins, thereby reinstating p53 functionality to induce cell cycle arrest and apoptosis. Additionally, this compound impedes cell migration and invasion, exhibiting notable antitumor activity [1].

PROTAC MDM2 Degrader-2 is a compound designed utilizing PROTAC technology, functioning as a MDM2 degrader. Comprised of a highly potent inhibitor targeting MDM2, a linker, and the MDM2 ligand for E3 ubiquitin ligase, this compound facilitates the degradation of MDM2[1].

MDM2/XIAP-IN-2 is a dual inhibitor targeting murine double minute 2 (MDM2) and X-linked inhibitor of apoptosis protein (XIAP). It promotes the degradation of MDM2 and impedes translation of XIAP mRNA, effectively inhibiting cancer cell proliferation. Notably, it exhibits potent activity against the acute lymphoblastic leukemia cell line EU-1, with an IC50 of 0.3 μM [1].

MDM2/4-p53-IN-2 (2q) is a potent dual inhibitor of MDM2/MDM4 and activator of p53, demonstrating IC50 values of 70.7 nM for MDM2-p53 and 81.4 nM for MDM4-p53 complexes. It facilitates cell cycle regulation, promotes apoptosis, and exhibits anticancer properties [1].

rel-MDM2/4-p53-IN-2 (2q) is a potent dual MDM2/MDM4 inhibitor and p53 activator that acts on both the MDM2-p53 complex (IC50: 70.7 nM) and the MDM4-p53 complex (IC50: 81.4 nM). rel-MDM2/4-p53-IN-2 is capable of regulating cell cycle, induce apoptosis, and exhibit anti-cancer effects.

p53-Mdm2 inhibitor 4 inhibits the p53-MDM2 protein-protein interaction.

MDM2-IN-21 is a potent MDM2 inhibitor. MDM2-IN-21 can be used for the research of cancer.

MDM2/XIAP-IN-1 (compound 14) is an orally active dual inhibitor of MDM2 and XIAP, exhibiting anti-cancer activity with an IC50 of 0.3 μM and potential applications in cancer research [1].

PROTAC MDM2 Degrader-4 is a compound designed using PROTAC technology to degrade MDM2. It combines a powerful MDM2 inhibitor, a linker, and the MDM2 ligand for E3 ubiquitin ligase[1].

p53 and MDM2 proteins-interaction-inhibitor (racemic) is an inhibitor of the interaction between p53 and MDM2 proteins.

p53-MDM2-IN-1 (Example 30), an inhibitor targeting the p53-MDM2 X protein interaction, exhibits a K i value of 23.35 µM. This compound holds potential for applications in anti-tumor research.

MDM2-IN-1 is a synthetic MDM2-p53 interaction (MDM2) inhibitor and contains the trans (D-)configuration.

MDM2-p53-IN-1b is the MDM2-p53 interaction inhibitor.

rel-MDM2/4-p53-IN-3 is an MDM2/4-p53 protein-protein interaction (PPI) inhibitor that acts on MDM2-p53 and MDM4-p53 with IC50 values of 18.5 nM and 14.8 nM, respectively. rel-MDM2/4-p53-IN-3 can be used to study cancers, such as colon cancer.

MDM2/XIAP-IN-3 (compound 3e), a dual inhibitor of MDM2/XIAP, diminishes MDM2 and XIAP protein levels while augmenting p53 expression, consequently suppressing cancer cell proliferation and inducing apoptosis [1].

p53 and MDM2 proteins-interaction-inhibitor dihydrochloride is a interaction inhibitor between p53 and MDM2 proteins.

PROTAC MDM2 Degrader-1 is a chemical compound that utilizes PROTAC technology to degrade MDM2. This compound is comprised of a highly effective MDM2 inhibitor, a linker, and the MDM2 ligand for E3 ubiquitin ligase[1].

MDM2/4-p53-IN-3, an inhibitor of MDM2/4-p53 protein-protein interactions (PPIs), exhibits potent activity with IC50 values of 18.5 nM for MDM2-p53 and 14.8 nM for MDM4-p53. This compound is applicable in cancer research, including studies on colon cancer [1].

PROTAC MDM2 Degrader-3 is a compound that leverages PROTAC technology to degrade MDM2. It consists of a highly effective MDM2 inhibitor, a linker, and the MDM2 ligand for E3 ubiquitin ligase[1].

MDM2-p53-IN-16 is a potent inhibitor of the MDM2-p53 complex, exhibiting an IC 50 value of 4.3 nM for the dissociation of the human p53/MDM2 complex. It effectively reactivates p53, leading to apoptosis and cell-cycle arrest in Glioblastoma Multiforme (GBM) cells, positioning it as a valuable agent for cancer research.

Nutlin Carboxylic Acid (MDM2 ligand 1), derived from Nutlin 3, serves as an MDM2 ligand. It can be attached to a protein ligand via a linker to create PROTACs[1].

HOXB7 8–25 (MDM2 32-46) is a peptide epitope derived from MDM2 that can induce both antigen-specific and tumor-reactive CD4+ T cell responses [1].

(4R,5S)-Nutlin Carboxylic Acid (MDM2 Ligand 2), a Nutlin 3-based MDM2 ligand, can be conjugated to a protein-binding ligand via a linker to create PROTACs[1].

Nutlin-C1-amido-PEG4-C2-N3 is a novel compound that functions as a ligand-linker conjugate for the E3 ligase. It is a synthesized molecule incorporating the MDM2 ligand derived from Nutlin 3, and a 4-unit PEG linker. This compound is specifically designed for utilization in PROTAC technology.

Alrizomadlin (APG-115) is an orally active inhibitor of MDM2 with IC50 of 3.8 nM and Ki of 1 nM, respectively[1]. Alrizomadlin blocks the interaction of MDM2 and p53 and induces cell-cycle arrest and apoptosis in a p53-dependent manner.

Navtemadlin (AMG232) is a potent, selective and orally available inhibitor of p53-MDM2 interaction (IC50: 0.6 nM). It binds to MDM2 with a Kd of 0.045 nM.

RDR03871 is an MDM2 inhibitor.

Milademetan (DS-3032) is an orally active and potent MDM2 inhibitor with antitumor activity that induces G1 cell cycle arrest, senescence, and apoptosis.Milademetan is used in the study of acute myeloid leukemia and solid tumors.

RO-5963 is a dual inhibitor of p53-MDM2 and p53-MDMX (IC50s: ~17 nM and ~24 nM, respectively).

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

Nutlin-3 is an MDM2 antagonist.Nutlin-3 inhibits the MDM2-p53 interaction (IC50: 0.09 μM) and activates p53. Antiproliferative agent; chemotherapeutic agent; induces apoptosis in Y cells.

Vanillin (Zimco) is a single molecule extracted from vanilla beans and also a popular odor used widely in perfume, food and medicine.Vanillin can reversibly and non-competitively inhibit the cellulase activity at appropriate concentrations and the value of IC50 was estimated to be 30 g/L.Vanillin protects KSC from UVB irradiation and its effects may occur through the suppression of downstream step of MDM2 in UVB irradiation-induced p53 activation. Vanillin also inhibits yeast growth and fermentation.

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.

RITA (NSC-652287)(NSC-652287) induced cross-links of both DNA-DNA and DNA-protein with no detectable DNA single-strand breaks. RITA, like nutlin-3, can disrupt the p53/Mdm2 interaction.

Idasanutlin (Ro 5503781) (RG-7388) is an effective and specific p53-MDM2 inhibitor (IC50: 6 nM).

Triptolide (PG490) belongs to the tricyclic diterpenoid group of natural products and is an inhibitor of NF-κB activation. Triptolide exhibits immunosuppressive, anti-rheumatic, anti-inflammatory, anti-proliferative and anti-tumor activities.

FAK ligand-Linker Conjugate 1 is a chemical compound designed to facilitate PROTAC-mediated protein degradation. This compound consists of a ligand specifically targeting FAK and a PROTAC linker module, which acts as a recruitment agent for E3 ligases including VHL, CRBN, MDM2, and IAP[1].

Cis,trans-Germacrone, an isomer of Germacrone, demonstrates extensive antitumor, antioxidant, and anti-inflammatory properties. It hinders lung cancer cell proliferation and impacts the Akt/MDM2/p53 pathway. Additionally, Germacrone induces cell cycle arrest at the G1/S phase [1].

Nutlin-3b ((+)-Nutlin-3) is a p53/MDM2 antagonist or inhibitor (IC50: 13.6 μM), 150-fold less potent (+)-enantiomer of Nutlin-3 as in comparison with opposite (-)-enantiomer Nutlin-3a.

K-Ras ligand-Linker Conjugate 6 is a chemical compound that combines a ligand for K-Ras recruiting moiety and a PROTAC linker. This compound can recruit E3 ligases, including VHL, CRBN, MDM2, and IAP. K-Ras ligand-Linker Conjugate 6 is particularly useful in the synthesis of PROTAC K-Ras Degrader-1, a highly effective K-Ras degrader that achieves ≥70% degradation efficacy in SW1573 cells[1].

Illudin S (ILS) is a fungal sesquiterpene secondary metabolite with potent genotoxic and cytotoxic properties.

Ganoderic acid X is a potential Mdm2 inhibitor(K(i) = 16nM). It is a potential anticancer drug, inhibits topoisomerases and induces apoptosis of cancer cells.

Sulanemadlin (ALRN-6924) is a potent peptidomimetic macrocycle that serves as an inhibitor of the p53-MDM2 and p53-MDMX protein-protein interactions. It is capable of inhibiting either or both of these interactions, positioning it as a valuable tool for cancer research [1].

Aciculatin is a natural compound.It also shows potent anti-cancer potency. Aciculatin treatment induces cell cycle arrest and apoptosis via inhibition of MDM2 expression without significant DNA damage and genome toxicity.

MI-773 is a potent inhibitor of the MDM2-p53 protein interaction (PPI) with a high affinity for MDM2 and a Kd value of 8.2 nM. MI-773 exhibits antitumour effects.

MeOIstPyrd is an anti-skin cancer agent that inhibits cell proliferation, migration, and spheroid formation through activation of the mitochondrial intrinsic apoptotic pathway. It induces DNA damage, activates p53, prolongs its half-life, and stabilizes p53 via ser15 phosphorylation. Additionally, MeOIstPyrd interfaces with MDM2 within the p53 sub-pocket, preventing the p53-MDM2 interaction [1].

PTK7/β-catenin-IN-1 (compound 01065) is a potent inhibitor targeting PTK7/β-catenin and p53/MDM2, with IC50 values of 8.9 μM and 56.5 μM, respectively. This compound shows promise for cancer research applications [1].

MD-222, a pioneering, highly potent PROTAC degrader targeting MDM2, efficiently mediates the rapid degradation of MDM2 protein and activates wild-type p53 within cells, showcasing significant anticancer effects[1][2].

MI-888 is a potent MDM2 inhibitor (Ki = 0.44 nM) with a superior pharmacokinetic profile and enhanced in vivo efficacy. MI-888 is capable of achieving rapid, complete, and durable tumor regression in two types of xenograft models of human cancer with oral administration and represents the most potent and efficacious MDM2 inhibitor reported to date.

K-Ras ligand-Linker Conjugate 4 is a chemical compound that combines a ligand for K-Ras recruiting moiety with a PROTAC linker. This linker is responsible for recruiting E3 ligases such as VHL, CRBN, MDM2, and IAP. The compound has the potential to be used in the synthesis of PROTAC K-Ras Degrader-1, a powerful degrader of K-Ras that has been shown to exhibit a degradation efficacy of ≥70% in SW1573 cells[1].