Browsing by Author "Liu, Yan"

Now showing 1 - 3 of 3
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    Cyclic Marinopyrrole Derivatives as Disruptors of Mcl-1 and Bcl-xL Binding to Bim
    (MDPI, 2014) Cheng, Chunwei; Liu, Yan; Balasis, Maria E.; Simmons, Nicholas L.; Li, Jerry; Song, Hao; Pan, Lili; Qin, Yong; Nicolaou, K.C.; Sebti, Said M.; Li, Rongshi
    A series of novel cyclic marinopyrroles were designed and synthesized. Their activity to disrupt the binding of the pro-apoptotic protein, Bim, to the pro-survival proteins, Mcl-1 and Bcl-xL, was evaluated using ELISA assays. Both atropisomers of marinopyrrole A (1) show similar potency. A tetrabromo congener 9 is two-fold more potent than 1. Two novel cyclic marinopyrroles (3 and 4) are two- to seven-fold more potent than 1.
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    Implementation of multiple-corrections and presolve enhancement in the interior-point linear programming code LIPSOL
    (1999) Liu, Yan; Zhang, Yin
    Multiple correction was introduced by Gondzio (5) to accelerate the convergence of iterates generated by primal-dual interior-point algorithms for linear programming. In this work, we implement the multiple correction technique in the interior-point linear programming software LIPSOL with our modifications. In our implementation, we have used modified criteria to start and stop the multiple correction process in order to achieve high efficiency under the LIPSOL environment. In addition, we have implemented a more thorough presolve analysis to enhance the solver's efficiency. The main presolve technique addressed in this work is to eliminate implied free variables. We have performed extensive computational experiments on the Netlib set of linear programs as well as on some larger linear programs from real-world applications. On the average, our implementation of the enhanced presolve and the multiple correction technique has resulted in a 10% to 20% saving in CPU time.
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    Marinopyrrole Derivatives with Sulfide Spacers as Selective Disruptors of Mcl-1 Binding to Pro-Apoptotic Protein Bim
    (MDPI, 2014) Cheng , Chunwei; Liu, Yan; Balasis, Maria E.; Garner, Thomas P.; Li, Jerry; Simmons, Nicholas L.; Berndt, Norbert; Song, Hao; Pan, Lili; Qin, Yong; Nicolaou, K.C.; Gavathiotis, Evripidis; Sebti , Said M.; Li, Rongshi; BioScience Research Collaborative
    A series of novel marinopyrroles with sulfide and sulphone spacers were designed and synthesized. Their activity to disrupt the binding of the pro-apoptotic protein, Bim, to the pro-survival proteins, Mcl-1 and Bcl-xL, was evaluated using ELISA assays. Fluorescence-quenching (FQ) assays confirmed the direct binding of marinopyrroles to Mcl-1. Benzyl- and benzyl methoxy-containing sulfide derivatives 4 and 5 were highly potent dual Mcl-1/Bim and Bcl-xL/Bim disruptors (IC50 values of 600 and 700 nM), whereas carboxylate-containing sulfide derivative 9 exhibited 16.4-fold more selectivity for disrupting Mcl-1/Bim over Bcl-xL/Bim binding. In addition, a nonsymmetrical marinopyrrole 12 is as equally potent as the parent marinopyrrole A (1) for disrupting both Mcl-1/Bim and Bcl-xL/Bim binding. Some of the derivatives were also active in intact human breast cancer cells where they reduced the levels of Mcl-1, induced programd cell death (apoptosis) and inhibited cell proliferation.