Discovery of potent and selective inhibitors of ataxia telangiectasia mutated and Rad3 related (ATR) protein kinase as potential anticancer agents.

DNA-damaging agents are among the most frequently used anticancer drugs. However, they provide only modest benefit in most cancers. This may be attributed to a genome maintenance network, the DNA damage response (DDR), that recognizes and repairs damaged DNA.

Investigation of the terminal P4 domain in a series of D-phenylglycinamide-based factor Xa inhibitors.

Several P4 domain derivatives of the general d-phenylglycinamide-based scaffold (2) were synthesized and evaluated for their ability to bind to the serine protease factor Xa. Some of the more potent compounds were evaluated for their anticoagulant effects in vitro. A select subset containing various P1 indole constructs was further evaluated for their pharmacokinetic properties after oral administration to rats.

A four component coupling strategy for the synthesis of D-phenylglycinamide-derived non-covalent factor Xa inhibitors.

A novel isonitrile derivative was synthesized and used in an Ugi four component coupling reaction to explore aryl group substitution effects on inhibition of the coagulation cascade serine protease factor Xa.

Plasticity and learning in a network of coupled phase oscillators.

A generalized Kuramoto model of coupled phase oscillators with a slow varying coupling matrix is studied. The dynamics of the coupling coefficients is driven by the phase difference of pairs of oscillators in such a way that the coupling strengthens for synchronized oscillators and weakens for nonsynchronized pairs. The system possesses a family of stable solutions corresponding to synchronized clusters of different sizes.

PRO_SELECT: combining structure-based drug design and array-based chemistry for rapid lead discovery. 2. The development of a series of highly potent and selective factor Xa inhibitors.

In silico screening of combinatorial libraries prior to synthesis promises to be a valuable aid to lead discovery. PRO_SELECT, a tool for the virtual screening of libraries for fit to a protein active site, has been used to find novel leads against the serine protease factor Xa. A small seed template was built upon using three iterations of library design, virtual screening, synthesis, and biological testing.