• Publications
  • Influence
An ATP-competitive Mammalian Target of Rapamycin Inhibitor Reveals Rapamycin-resistant Functions of mTORC1*
TLDR
It is found that Torin1, a highly potent and selective ATP-competitive mTOR inhibitor that directly inhibits both complexes, impairs cell growth and proliferation to a far greater degree than rapamycin.
Targeting transcription regulation in cancer with a covalent CDK7 inhibitor
TLDR
The discovery and characterization of a covalent CDK7 inhibitor, THZ1, is presented, which has the unprecedented ability to target a remote cysteine residue located outside of the canonical kinase domain, providing an unanticipated means of achieving selectivity forCDK7.
Targeting Bcr–Abl by combining allosteric with ATP-binding-site inhibitors
TLDR
The results show that therapeutically relevant inhibition of Bcr–Abl activity can be achieved with inhibitors that bind to the myristate-binding site and that combining allosteric and ATP-competitive inhibitors can overcome resistance to either agent alone.
Allosteric inhibitors of Bcr-abl–dependent cell proliferation
TLDR
The discovery of a new class of Bcr-abl inhibitors is reported using an unbiased differential cytotoxicity screen of a combinatorial kinase-directed heterocycle library and it is proposed that this newclass of compounds inhibits BCr-abl kinase activity through an allosteric non-ATP competitive mechanism.
Small Molecule Kinase Inhibitors Provide Insight into Mps1 Cell Cycle Function
TLDR
Chemical inhibition of Mps1 leads to defects in Mad1 and Mad2 establishment at unattached kinetochores, decreased Aurora B kinase activity, premature mitotic exit, and gross aneuploidy, however, in U2OS cells possessing extra centrosomes, an abnormality found in some cancers, MPS1 inhibition increases the frequency of multipolar mitoses.
Therapeutic targeting of oncogenic K-Ras by a covalent catalytic site inhibitor.
TLDR
These first-in-class covalent K-Ras inhibitors demonstrate that irreversible targeting of the K- Ras guanine-nucleotide binding site is potentially a viable therapeutic strategy for inhibition of Ras signaling.
Acquired METD1228V Mutation and Resistance to MET Inhibition in Lung Cancer.
TLDR
It is demonstrated that an acquired METD1228V mutation mediates resistance to type I, but not type II, MET inhibitors, having therapeutic implications for the clinical use of sequential MET inhibitors.
Development of covalent inhibitors that can overcome resistance to first-generation FGFR kinase inhibitors
  • L. Tan, Jun Wang, N. Gray
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences
  • 27 October 2014
TLDR
FIIN-2 and FIIN-3 are the first inhibitors that can potently inhibit the proliferation of cells dependent upon the gatekeeper mutants of FGFR1 or FGFR2, which confer resistance to first-generation clinical FGFR inhibitors such as NVP-BGJ398 and AZD4547.
Development of Chemical Probes for Investigation of Salt-Inducible Kinase Function in Vivo.
TLDR
In vivo active doses of YKL-05-099 recapitulate the effects of SIK inhibition on inflammatory cytokine responses, but do not induce metabolic abnormalities observed in Sik2 knockout mice, which support the development of Sik inhibitors for treatment of inflammatory disorders.
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