Schnekenburger, Michael Goffin, Eric Lee, Jin-Young Young Jang, Jun Mazumder, Aloran Ji, Seungwon Rogister, Bernard Bouider, Nafila Lefranc, Florence Miklos, Walter
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Published in
Journal of Medicinal Chemistry
in May 09, 2017
A new series of N-aryl-N'-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)ureas bearing an alkoxycarbonylamino group at the 6-position were synthesized and examined as putative anticancer agents targeting sirtuins in glioma cells. Based on computational docking combined to in vitro sirtuin 1/2 inhibition assays, we selected compound 18 [R/S-N-3-cyano...
Dong Jae Baek Neil MacRitchie Nahoum G. Anthony Simon P. Mackay Susan Pyne Nigel J. Pyne Robert Bittman
Published in
Journal of Medicinal Chemistry
in Oct 28, 2013
The design, synthesis, and evaluation of the potency of new isoform-selective inhibitors of sphingosine kinases 1 and 2 (SK1 and SK2), the enzyme that catalyzes the phosphorylation of d-erythro-sphingosine to produce the key signaling lipid, sphingosine 1-phosphate, are described. Recently, we reported that 1-(4-octylphenethyl)piperidin-4-ol (RB-00...
Fei Yang Nicholas G. Nickols Benjamin C. Li Jerzy O. Szablowski Shari R. Hamilton Jordan L. Meier Chieh-Mei Wang Peter B. Dervan
Published in
Journal of Medicinal Chemistry
in Sep 09, 2013
A hairpin pyrrole-imidazole polyamide (1) targeted to the androgen receptor consensus half-site was found to exert antitumor effects against prostate cancer xenografts. A previous animal study showed that 1, which has a chiral amine at the α-position of the γ-aminobutyric acid turn (γ-turn), did not exhibit toxicity at doses less than 10 mg/kg. ...
Matthew Merski Brian K. Shoichet
Published in
Journal of Medicinal Chemistry
in Aug 03, 2013
Simplified model binding sites allow one to isolate entangled terms in molecular energy functions. Here, we investigate the effects on ligand recognition of the introduction of a histidine into a hydrophobic cavity in lysozyme. We docked 656040 molecules and tested 26 highly and nine poorly ranked. Twenty-one highly ranked molecules bound and five ...
Michael Chan Tomoko Hayashi Richard D. Mathewson Afshin Nour Yuki Hayashi Shiyin Yao Rommel I. Tawatao Brian Crain Igor F. Tsigelny Valentina L. Kouznetsova
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Published in
Journal of Medicinal Chemistry
in Jun 13, 2013
A cell-based high-throughput screen to identify small molecular weight stimulators of the innate immune system revealed substituted pyrimido[5,4-b]indoles as potent NFκB activators. The most potent hit compound selectively stimulated Toll-like receptor 4 (TLR4) in human and mouse cells. Synthetic modifications of the pyrimido[5,4-b]indole scaffold...
Jonathan M. Elkins Jing Wang Xianming Deng Michael J. Pattison J. Simon C. Arthur Tatiana Erazo Nestor Gomez Jose M. Lizcano Nathanael S. Gray Stefan Knapp
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Published in
Journal of Medicinal Chemistry
in Jun 13, 2013
The protein kinase ERK5 (MAPK7) is an emerging drug target for a variety of indications, in particular for cancer where it plays a key role mediating cell proliferation, survival, epithelial–mesenchymal transition, and angiogenesis. To date, no three-dimensional structure has been published that would allow rational design of inhibitors. To addre...
Vassilios Bavetsias Amir Faisal Simon Crumpler Nathan Brown Magda Kosmopoulou Amar Joshi Butrus Atrash Yolanda Pérez-Fuertes Jessica A. Schmitt Katherine J. Boxall
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Published in
Journal of Medicinal Chemistry
in Jun 11, 2013
Aurora-A differs from Aurora-B/C at three positions in the ATP-binding pocket (L215, T217, and R220). Exploiting these differences, crystal structures of ligand–Aurora protein interactions formed the basis of a design principle for imidazo[4,5-b]pyridine-derived Aurora-A-selective inhibitors. Guided by a computational modeling approach, appropria...
Julie A. Spicer Gersande Lena Dani M. Lyons Kristiina M. Huttunen Christian K. Miller Patrick D. O’Connor Matthew Bull Nuala Helsby Stephen M. F. Jamieson William A. Denny
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Published in
Journal of Medicinal Chemistry
in Jun 11, 2013
A series of novel 5-arylidene-2-thioxoimidazolidin-4-ones were investigated as inhibitors of the lymphocyte-expressed pore-forming protein perforin. Structure–activity relationships were explored through variation of an isoindolinone or 3,4-dihydroisoquinolinone subunit on a fixed 2-thioxoimidazolidin-4-one/thiophene core. The ability of the resu...
Shailesh N. Mistry Jillian G Baker Peter M Fischer Stephen J Hill Sheila M Gardiner Barrie Kellam
Published in
Journal of Medicinal Chemistry
in Apr 24, 2013
β-Adrenoceptor antagonists boast a 50-year use for symptomatic control in numerous cardiovascular diseases. One might expect highly selective antagonists are available for the human β-adrenoceptor subtype involved in these diseases, yet few truly β1-selective molecules exist. To address this clinical need, we re-evaluated LK 204-545 (1),1 a sele...
Dinakaran Murugesan Alka Mital Marcel Kaiser David M. Shackleford Julia Morizzi Kasiram Katneni Michael Campbell Alan Hudson Susan A. Charman Clive Yeates
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Published in
Journal of Medicinal Chemistry
in Mar 21, 2013
In the pursuit of new antimalarial leads, a phenotypic screening of various commercially sourced compound libraries was undertaken by the World Health Organisation Programme for Research and Training in Tropical Diseases (WHO-TDR). We report here the detailed characterization of one of the hits from this process, TDR32750 (8a), which showed potent ...