A. W. Partridge

Design-Rules for Stapled Alpha-Helical Peptides with On-Target In Vivo Activity: Application toMdm2/X dual antagonists

The paper develops design rules for stapled alpha-helical peptides to improve in vivo activity and reduce off-target effects, demonstrating significant improvements in potency and safety.

Targeted degradation of PCNA outperforms stoichiometric inhibition to result in programed cell death

This study shows that targeted degradation of PCNA via biodegraders leads to more effective anti-proliferative effects and programmed cell death compared to stoichiometric inhibition.

Discovery of cell active macrocyclic peptides with on-target inhibition of KRAS signaling

This paper identifies macrocyclic peptides that inhibit KRAS signaling by binding to its hydrophobic pocket, showing on-target activity and improved proteolytic stability.

STUB1 is an intracellular checkpoint for interferon gamma sensing

This study identifies STUB1 as a barrier to interferon gamma sensing, showing it dampens IFNγ response through reduced IFNGR1 surface abundance, but in vivo STUB1 inactivation did not improve ICB outcomes in mouse models.

bioPROTACs establish RAS as a degradable target and provide novel RAS biology insights

The paper demonstrates that RAS proteins can be degraded using bioPROTACs and provides insights into the functional consequences of RAS degradation and mutant susceptibility.

bioPROTACs as versatile modulators of intracellular therapeutic targets: Application to proliferating cell nuclear antigen (PCNA)

This paper introduces bioPROTACs as intracellular biologics for targeted protein degradation, demonstrating their effectiveness against PCNA with rapid degradation and functional effects.

De-risking drug discovery of intracellular targeting peptides: screening strategies to eliminate false-positive hits

This paper identifies false-positive peptide inhibitors of KRas using orthogonal assays and cellular screens, highlighting the need for rigorous validation in drug discovery.