Lead optimization and modulation of hERG activity in a series of aminooxazoline xanthene β-site amyloid precursor protein cleaving enzyme (BACE1) inhibitors.
Epstein O, Bryan MC, Cheng AC, Derakhchan K, Dineen TA, Hickman D, Hua Z, Human JB, Kreiman C, Marx IE, Weiss MM, Wahl RC, Wen PH, Whittington DA, Wood S, Zheng XM, Fremeau RT Jr, White RD, Patel VF.
J Med Chem. 57, 9796-810 (2014)   Link


Inhibitors of β-Site amyloid precursor protein cleaving enzyme (BACE1): Identification of (S)-7-(2-fluoropyridin-3-yl)-3-((3-methyloxetan-3-yl)ethynyl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-2'-amine (AMG-8718).
Dineen TA, Chen K, Cheng AC, Derakhchan K, Epstein O, Esmay J, Hickman D, Kreiman CE, Marx IE, Wahl RC, Wen PH, Weiss MM, Whittington DA, Wood S, Fremeau RT Jr, White RD, Patel VF.
J Med Chem. 57, 9811-31 (2014)   Link


Structure-based druggability assessment of the mammalian structural proteome with inclusion of light protein flexibility.
Loving KA, Lin A, Cheng AC.
PLoS Comput Biol. 10, e1003741 (2014)   Link


Structure guided design of a series of sphingosine kinase (SphK) inhibitors.
Gustin DJ, Li Y, Brown ML, Min X, Schmitt MJ, Wanska M, Wang X, Connors R, Johnstone S, Cardozo M, Cheng AC, Jeffries S, Franks B, Li S, Shen S, Wong M, Wesche H, Xu G, Carlson TJ, Plant M, Morgenstern K, Rex K, Schmitt J, Coxon A, Walker N, Kayser F, Wang Z.
Bioorg Med Chem Lett. 23, 4608-4616 (2013)   Link


Structure- and property-based design of aminooxazoline xanthenes as selective, orally efficacious, and CNS penetrable BACE inhibitors for the treatment of Alzheimer's Disease.
Huang H, La DS, Cheng AC, Whittington DA, Patel VF, Chen K, Dineen TA, Epstein O, Graceffa R, Hickman D, Kiang YH, Louie S, Luo Y, Wahl RC, Wen PH, Wood S, Fremeau RT Jr.
J Med Chem.   55, 9156-9169 (2012)   Link


Discovery and optimization of potent and selective imidazopyridine and imidazopyridazine mTOR inhibitors.
Peterson EA, Boezio AA, Andrews PS, Boezio CM, Bush TL, Cheng AC, Choquette D, Coats JR, Colletti AE, Copeland KW, DuPont M, Graceffa R, Grubinska B, Kim JL, Lewis RT, Liu J, Mullady EL, Potashman MH, Romero K, Shaffer PL, Stanton MK, Stellwagen JC, Teffera Y, Yi S, Cai T, La DS.
Bioorg Med Chem Lett.   22, 4967-4974 (2012)   Link


Rapid development of piperidine carboxamides as potent and selective Anaplastic Lymphoma Kinase inhibitors
Bryan MC, Whittington DA, Doherty EM, Falsey JR, Cheng AC, Emkey R, Brake RL, Lewis RT.
J Med Chem.   55, 1698-1705 (2012)   Link


Fragment based drug discovery: Practical implementation based on 19F NMR spectroscopy
Jordan JB, Poppe L, Xia X, Cheng AC, Sun Y, Michelsen K, Eastwood H, Schnier PD, Nixey T, Zhong W.
J Med Chem.   55, 678-687 (2012)   Link


Screening for lysine-specific demethylase-1 inhibitors using a label-free high-throughput mass spectrometry assay
Plant M, Dineen T, Cheng A, Long AM, Chen H, Morgenstern KA.
Anal Biochem.   419, 217-227 (2011)   Link


Benzodiazepinone derivatives as CRTH2 antagonists
Liu J, Cheng AC, Tang HL, Medina JC
ACS Med. Chem. Lett.   2, 515-518 (2011)   Link


Discovery of triazine-benzimidazoles as selective inhibitors of mTOR.
Peterson EA, Andrews PS, Be X, Boezio AA, Bush TL, Cheng AC, Coats JR, Colletti AE, Copeland KW, Dupont M, Graceffa R, Grubinska B, Harmange JC, Kim JL, Mullady EL, Olivieri P, Schenkel LB, Stanton MK, Teffera Y, Whittington DA, Cai T, La DS.
Bioorg Med Chem Lett.   21, 2064-2070(2011)   Link


Preparation, solid state characterization, and single crystal structure analysis of N-(4-(6-(4-(trifluoromethyl)phenyl)pyrimidin-4-yloxy)benzo[d]thiazol-2-yl)acetamide crystal forms.
Peterson ML, Stanton MK, Kelly RC, Staples R, Cheng A.
CrystEngComm.   13, 1170-1180 (2011)   Link


Discovery of a potent, selective, and orally bioavailable pyridinyl-pyrimidine phthalazine aurora kinase inhibitor.
Cee VJ, Schenkel LB, Hodous BL, Deak HL, Nguyen HN, Olivieri PR, Romero K, Bak A, Be X, Bellon S, Bush TL, Cheng AC, Chung G, Coats S, Eden PM, Hanestad K, Gallant PL, Gu Y, Huang X, Kendall RL, Lin MH, Morrison MJ, Patel VF, Radinsky R, Rose PE, Ross S, Sun JR, Tang J, Zhao H, Payton M, Geuns-Meyer SD.
J Med Chem.   53, 6368-6377 (2010)   Link


Enhanced selectivity profile of pyrazole-urea based DFG-out p38-alpha inhibitors.
Liu H, Kuhn C, Feru F, Jacques SL, Deshmukh GD, Ye P, Rennie GR, Johnson T, Kazmirski S, Low S, Coli R, Ding YH, Cheng AC, Tecle H, English JM, Stanton R, Wu JC.
Bioorg Med Chem Lett.   20, 4885-4891 (2010)   Link


Analysis of kinase inhibitor selectivity using a thermodynamics-based partition index
Cheng AC, Eksterowicz J, Geuns-Meyer S, Sun Y.
J Med Chem.   53, 4502-4510 (2010)   Link


The design, synthesis and potential utility of fluorescence probes that target DFG-out conformation of p38 for high throughput screening binding assay.
Tecle H, Feru F, Liu H, Kuhn C, Rennie G, Morris M, Shao J, Cheng AC, Gikunju D, Miret J, Coli R, Xi SH, Clugston SL, Low S, Kazmirski S, Ding YH, Cao Q, Johnson TL, Deshmukh GD, Dinitto JP, Wu JC, English JM.
Chem Biol Drug Des.   74, 547-559 (2009)   Link


On the nature of intermolecular interactions in nucleic acid base-amino acid side-chain complexes.
Czyznikowska Z, Lipkowski P, Gora RW, Zalesny R, Cheng AC.
J Phys Chem B.   113, 11511-11520 (2009)   Link


Quinazolin-4-piperidin-4-methyl sulfamide PC-1 inhibitors: Alleviating hERG interactions through structure based design.
Patel SD, Habeski WM, Cheng AC, de la Cruz E, Loh C, Kablaoui NM.
Bioorg Med Chem Lett.   19, 3339-3343 (2009)   Link


Identification of allosteric PIF-pocket ligands for PDK1 using NMR-based fragment screening and 1H-15N TROSY experiments.
Stockman BJ, Kothe M, Kohls D, Weibley L, Connolly BJ, Sheils AL, Cao Q, Cheng AC, Yang L, Kamath AV, Ding Y-H, Charlton ME.
Chem Biol Drug Des.   73, 179-188 (2009)   Link


Pyridyl-pyrimidine benzimidazole derivatives as potent, selective, and orally bioavailable inhibitors of Tie-2 kinase.
Cee VJ, Cheng AC, Romero K, Bellon S, Mohr C, Whittington DA, Bak A, Bready J, Caenepeel S, Coxon A, Deak HL, Fretland J, Gu Y, Hodous BL, Huang X, Kim JL, Lin J, Long AM, Nguyen H, Olivieri PR, Patel VF, Wang L, Zhou Y, Hughes P, Geuns-Meyer S.
Bioorg Med Chem Lett. 19, 424-7 (2009)   Link


Discovery of alpha-amidosulfones as potent and selective agonists of CB2: synthesis, SAR, and pharmacokinetic properties.
Marx IE, DiMauro EF, Cheng A, Emkey R, Hitchcock SA, Huang L, Huang MY, Human J, Lee JH, Li X, Martin MW, White RD, Fremeau RT Jr, Patel VF.
Bioorg Med Chem Lett.19, 31-35 (2009)   Link


Structural modifications of N-arylamide oxadiazoles: Identification of N-arylpiperidine oxadiazoles as potent and selective agonists of CB2.
DiMauro EF, Buchanan JL, Cheng A, Emkey R, Hitchcock SA, Huang L, Huang MY, Janosky B, Lee JH, Li X, Martin MW, Tomlinson SA, White RD, Zheng XM, Patel VF, Fremeau RT Jr.
Bioorg Med Chem Lett.18, 4267-4274 (2008)   Link


Predicting selectivity and druggability in drug discovery.
Cheng AC.
Annual Reports Comp Chem. 4, 23-37 (2008)   PDF   Link


N-(3-(phenylcarbamoyl)arylpyrimidine)-5-carboxamides as potent and selective inhibitors of Lck: structure, synthesis and SAR.
Deak HL, Newcomb JR, Nunes JJ, Boucher C, Cheng AC, DiMauro EF, Epstein LF, Gallant P, Hodous BL, Huang X, Lee JH, Patel VF, Schneider S, Turci SM, Zhu X.
Bioorg Med Chem Lett. 18, 1172-1176 (2008)   Link


Discovery of 4-amino-5,6-biaryl-furo[2,3-d]pyrimidines as inhibitors of Lck: development of an expedient and divergent synthetic route and preliminary SAR.
Dimauro EF, Newcomb J, Nunes JJ, Bemis JE, Boucher C, Buchanan JL, Buckner WH, Cheng A, Faust T, Hsieh F, Huang X, Lee JH, Marshall TL, Martin MW, McGowan DC, Schneider S, Turci SM, White RD, Zhu X.
Bioorg Med Chem Lett. 17, 2305-2309 (2007)   Link


Structure of the catalytic domain of human polo-like kinase 1.
Kothe M, Kohls D, Low S, Coli R, Cheng AC, Jacques SL, Johnson TL, Lewis C, Loh C, Nonomiya J, Sheils AL, Verdries KA, Wynn TA, Kuhn C, Ding YH.
Biochemistry. 46, 5960-5971 (2007)   Link


Structure-based maximal affinity model predicts small-molecule druggability.
Cheng AC, Coleman RG, Smyth KT, Cao Q, Soulard P, Caffrey DR, Salzberg AC, Huang ES.
Nature Biotechnology. 25, 71-75 (2007)   PDF   Link
    Highlighted in Nature Reviews Drug Discovery— Target Validation: Determining druggability. 6, 187 (2007) Link

Structure-based identification of small molecule binding sites using a free energy model.
Coleman RG, Salzberg AC, and Cheng AC.
J Chem Inf Model. 46, 2631-2637 (2006)   PDF   Link


Optimal charges in lead optimization: a structure-based neuraminidase case study.
Armstrong KA, Tidor B, and Cheng AC.
J Med Chem. 49, 2470-2477 (2006)   PDF   Link


An intuitive approach to measuring protein surface curvature.
Coleman RG, Burr MA, Souvaine DL, and Cheng AC.
Proteins. 61, 1068-1074 (2005)   PDF   Link


Transformations and algorithms for least sum of squares hypersphere fitting.
Coleman RG, Burr MA, Souvaine DL, Cheng AC.
Candadian Conf Comp Geom Proc.16, 104-107 (2004)   PDF   PS


Ab-initio interaction energies of amino acid side-chain hydrogen bond interactions with nucleic acid bases.
Cheng AC and Frankel AD.
J Am Chem Soc. 126, 434-435 (2004)   PDF   Link


Recognition of nucleic acid bases and base-pairs by hydrogen bonding to amino acid side-chains.
Cheng AC, Chen WW, Fuhrmann CN, and Frankel AD.
J Mol Biol. 327, 781-796 (2003)   PDF   Link
    Reviewed by Faculty of 1000 and highlighted as a "Must Read" (F1000 Factor 6.0). Link

Structural diversity and isomorphism of hydrogen-bonded base interactions in nucleic acids.
Walberer BJ, Cheng AC, and Frankel AD.
J Mol Biol. 327, 767-780 (2003)  
PDF   Link


Design of RNA-binding proteins and ligands.
Cheng AC, Calabro V, and Frankel AD.
Curr Opin Struct Biol. 11, 478-484 (2001)   PDF   Link