Search
Now showing items 1-10 of 17
Are Doses and Schedules of Small-Molecule Targeted Anticancer Drugs Recommended by Phase I Studies Realistic?
(AMER ASSOC CANCER RESEARCH, 2016-05-01)
Tolerability of molecularly targeted agents (MTA) used in cancer therapeutics is determined in phase I trials. We reviewed the reported incidence of toxicity in phase III trials at doses and schedules recommended by phase ...
Small-molecule targeting of brachyury transcription factor addiction in chordoma.
(2019-02)
Chordoma is a primary bone cancer with no approved therapy 1 . The identification of therapeutic targets in this disease has been challenging due to the infrequent occurrence of clinically actionable somatic mutations in ...
Integration of RNAi and Small Molecule Screens to Identify Targets for Drug Development.
(2019-01)
Cellular models for siRNA and small molecule high-throughput screening have been widely used in the last decade to identify targets for drug discovery. As an example, we present a twofold readout approach based on cell ...
On the origins of three-dimensionality in drug-like molecules.
(2016-09)
Aim Many medicinal chemistry-relevant structures and core scaffolds tend toward geometric planarity, which hampers the optimization of physicochemical properties desirable in drug-like molecules. As challenging drug target ...
Discovery of Potent, Selective, and Orally Bioavailable Small-Molecule Modulators of the Mediator Complex-Associated Kinases CDK8 and CDK19.
(AMER CHEMICAL SOC, 2016-02-11)
The Mediator complex-associated cyclin-dependent kinase CDK8 has been implicated in human disease, particularly in colorectal cancer where it has been reported as a putative oncogene. Here we report the discovery of 109 ...
Discovery of potent, orally bioavailable, small-molecule inhibitors of WNT signaling from a cell-based pathway screen.
(AMER CHEMICAL SOC, 2015-02-26)
WNT signaling is frequently deregulated in malignancy, particularly in colon cancer, and plays a key role in the generation and maintenance of cancer stem cells. We report the discovery and optimization of a 3,4,5-trisubstituted ...
Kinetic Optimization of Lysine-Targeting Covalent Inhibitors of HSP72.
(AMER CHEMICAL SOC, 2019-12-26)
The covalent inhibition mechanism of action, which overcomes competition with high-affinity, high-abundance substrates of challenging protein targets, can deliver effective chemical probes and drugs. The success of this ...
BRET-based RAS biosensors that show a novel small molecule is an inhibitor of RAS-effector protein-protein interactions.
(ELIFE SCIENCES PUBLICATIONS LTD, 2018-07-10)
The RAS family of proteins is amongst the most highly mutated in human cancers and has so far eluded drug therapy. Currently, much effort is being made to discover mutant RAS inhibitors and in vitro screening for RAS-binding ...
Small molecule inhibitors of RAS-effector protein interactions derived using an intracellular antibody fragment.
(NATURE PORTFOLIO, 2018-08-09)
Targeting specific protein-protein interactions (PPIs) is an attractive concept for drug development, but hard to implement since intracellular antibodies do not penetrate cells and most small-molecule drugs are considered ...
Discovery and Optimization of a Selective Ligand for the Switch/Sucrose Nonfermenting-Related Bromodomains of Polybromo Protein-1 by the Use of Virtual Screening and Hydration Analysis.
(AMER CHEMICAL SOC, 2016-10-13)
Bromodomains (BRDs) are epigenetic interaction domains currently recognized as emerging drug targets for development of anticancer or anti-inflammatory agents. In this study, development of a selective ligand of the fifth ...