nutlin 3

Nutlin-3 is an MDM2 antagonist that inhibits MDM2-p53 interaction (Ki=90 nM) and activates p53. Nutlin-3 binds preferentially to the p53-binding pocket of MDM2, leading to stabilization of p53 and activation of the p53 pathway. Nutlin-3 has antitumor activity.

Nutlin-C1-amido-PEG4-C2-N3 is a novel ligand-linker conjugate for the E3 ligase, incorporating the MDM2 ligand from Nutlin 3 and a 4-unit PEG linker. This compound is specifically designed for use in PROTAC technology.

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.

Nutlin-3a is the active enantiomer of Nutlin-3, an MDM2 antagonist that inhibits MDM2-p53 interaction (Ki=90 nM) and activates p53. Nutlin-3a binds preferentially to the p53-binding pocket of MDM2, leading to stabilization of p53 and activation of the p53 pathway. Nutlin-3a has antitumor activity.

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.

Nutlin-3 is an activator of p53 that functions by inhibiting the interaction of p53 with MDM2, a negative regulator of p53 activity. Caylin-1 is a nutlin-3 analog which contains chlorine substituents at the 3 and 4 positions on two of the phenyl rings rather than a single 4-chloro as seen in nutlin-3. At high concentrations, caylin-1 inhibits the growth of HCT116 cells with an IC50 value of approximately 7 μM, making it about 7-fold less potent than nutlin-3 in the same assay. Interestingly, at concentrations at or below 1 μM, caylin-1 promotes the growth of HCT116 cells approximately 20% compared to untreated cells. The mechanism of the growth promoting properties of caylin-1 have not yet been elucidated.

(±)-Nutlin-3 blocks the interaction of p53 with its negative regulator Mdm2 (IC50 = 90 nM), inducing the expression of p53-regulated genes and blocking the growth of tumor xenografts in vivo. CAY10682 is a pyrrolo[3,4c]pyrazole derivative that inhibits the p53-Mdm2 interaction as potently as (±)-nutlin-3 (Ki = 83 nM) and also dose-dependently reduces activation of the NF-κB pathway. It specifically prevents phosphorylation of IκBα by the kinases IKKα, IKKβ, and IKK (IC50s = 80.5, 78.2, and 57.1 μM, respectively). CAY10682 blocks the growth of cancer cells in vitro (IC50s = 2-6 μM) and inhibits the growth of A549 cell xenografts in mice without significantly reducing body weight.

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].

Nutlin-3 is an activator of p53 that functions by inhibiting the interaction of p53 with MDM2, a negative regulator of p53 activity. Caylin-2 is a nutlin-3 analog in which trifluoromethyl groups have been substituted for chlorine on the 2 phenyl rings. At high concentrations, caylin-2 inhibits the growth of HCT116 cells with an IC50 of approximately 8 μM, making it about 10-fold less potent than nutlin-3. Interestingly, at concentrations between 5-100 nM, caylin-2 promotes the growth of HCT116 cells approximately 40% compared to untreated cells. The mechanism of the growth promoting properties of caylin-2 have not yet been elucidated.

(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].