We recently reported the discovery of AM-8553 (<b>1</b>), a potent and selective piperidinone inhibitor of the MDM2–p53 interaction. Continued research investigation of the <i>N</i>-alkyl substituent of this series, focused in particular on a previously underutilized interaction in a shallow cleft on the MDM2 surface, led to the discovery of a one-carbon tethered sulfone which gave rise to substantial improvements in biochemical and cellular potency. Further investigation produced AMG 232 (<b>2</b>), which is currently being evaluated in human clinical trials for the treatment of cancer. Compound <b>2</b> is an extremely potent MDM2 inhibitor (SPR <i>K</i><sub>D</sub> = 0.045 nM, SJSA-1 EdU IC<sub>50</sub> = 9.1 nM), with remarkable pharmac...
The p53 pathway is disrupted in virtually every human tumor. In similar to 50% of human cancers, the...
P53 is a recognized tumor suppressor gene, which mainly depends on the activity of its transfer fact...
The MDM2 inhibitor AMG 232 demonstrates robust anti-tumor efficacy and potentiates the activity of p...
We previously reported the discovery of AMG 232, a highly potent and selective piperidinone inhibito...
Structure-based rational design and extensive structure–activity relationship studies led to the dis...
We previously reported the discovery of potent and selective morpholinone and piperidinone inhibitor...
p53 is a critical tumor suppressor and is the most frequently inactivated gene in human cancer. Inhi...
Continued optimization of the N-substituent in the piperidinone series provided potent piperidinone–...
The development of small-molecule MDM2 inhibitors to restore dysfunctional p53 activities represents...
Restoration of p53 activity by inhibition of the p53–MDM2 interaction has been considered an attract...
As a result of our efforts to discover novel p53:MDM2 protein–protein interaction inhibitors useful ...
As a result of our persistent efforts to discover novel inhibitors of the p53-MDM2 protein–protein i...
A new subseries of substituted piperidines as p53-HDM2 inhibitors exemplified by <b>21</b> has been ...
p53-Murine double minute 2 (MDM2) interaction and histone deacetylases (HDACs) are important targets...
Nowotwory są złożoną grupą wadliwych komórek, które stanowią zagrożenie dla życia człowieka. W celu ...
The p53 pathway is disrupted in virtually every human tumor. In similar to 50% of human cancers, the...
P53 is a recognized tumor suppressor gene, which mainly depends on the activity of its transfer fact...
The MDM2 inhibitor AMG 232 demonstrates robust anti-tumor efficacy and potentiates the activity of p...
We previously reported the discovery of AMG 232, a highly potent and selective piperidinone inhibito...
Structure-based rational design and extensive structure–activity relationship studies led to the dis...
We previously reported the discovery of potent and selective morpholinone and piperidinone inhibitor...
p53 is a critical tumor suppressor and is the most frequently inactivated gene in human cancer. Inhi...
Continued optimization of the N-substituent in the piperidinone series provided potent piperidinone–...
The development of small-molecule MDM2 inhibitors to restore dysfunctional p53 activities represents...
Restoration of p53 activity by inhibition of the p53–MDM2 interaction has been considered an attract...
As a result of our efforts to discover novel p53:MDM2 protein–protein interaction inhibitors useful ...
As a result of our persistent efforts to discover novel inhibitors of the p53-MDM2 protein–protein i...
A new subseries of substituted piperidines as p53-HDM2 inhibitors exemplified by <b>21</b> has been ...
p53-Murine double minute 2 (MDM2) interaction and histone deacetylases (HDACs) are important targets...
Nowotwory są złożoną grupą wadliwych komórek, które stanowią zagrożenie dla życia człowieka. W celu ...
The p53 pathway is disrupted in virtually every human tumor. In similar to 50% of human cancers, the...
P53 is a recognized tumor suppressor gene, which mainly depends on the activity of its transfer fact...
The MDM2 inhibitor AMG 232 demonstrates robust anti-tumor efficacy and potentiates the activity of p...