Theme：Does p53 targeted compound come out in China?

Host：Min Lu, Ph.D.

Time：26th September, 2019 , 10:00-11:40 

Location: Room 204, Engineering Building, Xuhui Campus, SJTU

Abstract: 

So far, approx. 82 targeted drugs are approved for cancer treatment, yet only about 3-12% cancer patients have targeted drug to use. p53 is mutated in half of all cancer cases worldwide, making it being the grail of targeted therapy. p53 is a tumor suppressor, a transcription factor, and a ‘smooth’ protein apparently without binding pocket, making it ‘undruggable’. At least 45 groups in the past 39 years have been working with p53 mutation-based therapy, yet it is still far from achieving an p53-targeted drug. In our group, many small-molecule compounds are either hit in screening or rationally synthesized. In assays quantitively comparing with wild-type p53, these compounds efficiently enhance a batch of structural mutant p53’s thermal stability (5-6 ℃), protein folding (fully restored PAb1620 epitope), transcriptional activity (fully restored transcriptional activity in luciferase assay, fully restored express profile of p53 targets in RNAseq), tumor-suppressive functions (selective to structural mp53). The talk with be ended with atom-level rescue mechanism, progresses in industry, and progresses in clinical trial.

Biography: 

Min Lu committed himself to the field of targeted therapy, specializing in restoring tumor-suppressive function to p53 using small-molecule compounds. The long-term goal of his group is to obtain the ‘grail’ of targeted therapy, the p53 targeted drug. As a postdoctor in Ludwig Institute for Cancer Research at Oxford, he revealed an iASPP-mediated wild-type p53 dysfunction and successfully identified compounds restoring tumor-suppressive function to wild-type p53 in metastatic melanoma. As a PI in Ruijin Hospital at Shanghai, his group identified a batch of first-in-class compounds that fully rescue a batch of structural mutant p53’s thermal stability, protein folding, and transcription activity, accompanied with an atomic-level mechanism. These compounds and various enhanced versions, derived from basic p53 research, are being translated into industry and clinic.