Xinlai Cheng

Junior Group Leader
Drug Development

Research Focus:

  • In vitro and in vivo chemical screening
  • Chemical synthesis and structure optimization
  • Target identification and validation

Expertise and Technologies for FCI:

  • Cell-based high throughput screening
  • Chemical and organic synthesis
  • PROTAC technology

Core Publications

  • A Chemical Toolbox for Labeling and Degrading Engineered Cas Proteins
    Rodrigo A Gama-Brambila, Jie Chen, Yasamin Dabiri, Georg Tascher, Václav Němec, Christian Münch, Guangqi Song, Stefan Knapp, Xinlai Cheng
    A proteome-wide analysis of PROTAC-FCPF-mediated Cas9FCPF protein degradation revealed a high target specificity, suggesting a wide range of applications of perfluoroaromatics-induced proximity in the regulation of stability, activity, and functionality of any FCPF-tagging protein. PubMed
  • A PROTAC targets splicing factor 3B1
    Rodrigo A Gama-Brambila, Jie Chen, Jun Zhou, Georg Tascher , Christian Münch, Xinlai Cheng
    Our finding demonstrates that SF3B1 is PROTACable by utilizing noninhibitory chemicals, which expands the list of PROTAC target proteins. PubMed
  • Imidazopyridines as Potent KDM5 Demethylase Inhibitors Promoting Reprogramming Efficiency of Human iPSCs
    Yasamin Dabiri, Rodrigo A. Gama-Brambila, Katerina Taskova, Kristina Herold, Stefanie Reuter, James Adjaye, Jochen Utikal, Ralf Mrowka, Jichang Wang, Miguel A. Andrade-Navarro, Xinlai Cheng
    Thus our results introduce a new class of KDM5 chemical inhibitors and provide further insight into the pluripotency-related properties of KDM5 family members. PubMed
See more Publications

Research Summary

Although rapidly developing genome sequencing technology has helped to reveal potential disease-causing proteins, for chemists it does not mean that an effective drug will be designed. Approved drugs currently cover only 10% of the human therapeutic proteome, probably because a classic chemical inhibitor requires a well-defined hydrophobic binding site on the surface of target protein, like growth factor receptors and protein kinase. Transcription factors and other proteins lacking a defined active site are still hardly druggable.

The major aim of my research is to develop small molecules targeting currently undruggable proteome in the fields of anti-cancer therapy, regenerative medicine and CRISPR-Cas-based biotechnology. Since 2019 my lab has established a number of approaches, spanning from medicinal chemistry to molecular biology and (epi)genome editing for the discovery of new drug-candidates.

Publications

  • A Chemical Toolbox for Labeling and Degrading Engineered Cas Proteins
    PubMed
  • A PROTAC targets splicing factor 3B1
    PubMed
  • Baicalein Induces Apoptosis of Pancreatic Cancer Cells by Regulating the Expression of miR-139-3p and miR-196b-5p
    PubMed
  • Liver-Kidney-on-Chip To Study Toxicity of Drug Metabolites
    PubMed
  • Methylisoindigo and Its Bromo-Derivatives Are Selective Tyrosine Kinase Inhibitors, Repressing Cellular Stat3 Activity, and Target CD133+ Cancer Stem Cells in PDAC
    PubMed
  • Valproic Acid Thermally Destabilizes and Inhibits SpyCas9 Activity
    PubMed
  • Yin Zhi Huang, a traditional Chinese herbal formula, ameliorates diet-induced obesity and hepatic steatosis by activating the AMPK/SREBP-1 and the AMPK/ACC/CPT1A pathways
    PubMed
  • NHC-gold compounds mediate immune suppression through induction of AHR-TGFβ1 signalling in vitro and in scurfy mice
    PubMed
  • Pro-oxidant and lifespan extension effects of caffeine and related methylxanthines in Caenorhabditis elegans
    PubMed
  • p53-Dependent Anti-Proliferative and Pro-Apoptotic Effects of a Gold(I) N-Heterocyclic Carbene (NHC) Complex in Colorectal Cancer Cells
    PubMed
  • In vitro metabolic activation of vitamin D3 by using a multi-compartment microfluidic liver-kidney organ on chip platform
    PubMed
  • Imidazopyridines as Potent KDM5 Demethylase Inhibitors Promoting Reprogramming Efficiency of Human iPSCs
    PubMed
  • A Ruthenium(II) N-Heterocyclic Carbene (NHC) Complex with Naphthalimide Ligand Triggers Apoptosis in Colorectal Cancer Cells via Activating the ROS-p38 MAPK Pathway
    PubMed
  • Fluorescent organometallic rhodium(I) and ruthenium(II) metallodrugs with 4-ethylthio-1,8-naphthalimide ligands: Antiproliferative effects, cellular uptake and DNA-interaction
    PubMed
  • Author Correction: Essential role of mitochondrial Stat3 in p38MAPK mediated apoptosis under oxidative stress
    PubMed
  • Monitoring cytochrome P450 activity in living hepatocytes by chromogenic substrates in response to drug treatment or during cell maturation
    PubMed
  • Essential role of mitochondrial Stat3 in p38MAPK mediated apoptosis under oxidative stress
    PubMed
  • The essential role of TAp73 in bortezomib-induced apoptosis in p53-deficient colorectal cancer cells
    PubMed
  • Identification of a Water-Soluble Indirubin Derivative as Potent Inhibitor of Insulin-like Growth Factor 1 Receptor through Structural Modification of the Parent Natural Molecule
    PubMed
  • Human microRNA-299-3p decreases invasive behavior of cancer cells by downregulation of Oct4 expression and causes apoptosis
    PubMed