Published in J Med Chem on September 15, 2014
Practical Strategies and Concepts in GPCR Allosteric Modulator Discovery: Recent Advances with Metabotropic Glutamate Receptors. Chem Rev (2016) 0.97
Further optimization of the M5 NAM MLPCN probe ML375: tactics and challenges. Bioorg Med Chem Lett (2014) 0.89
Molecular Insights into Metabotropic Glutamate Receptor Allosteric Modulation. Mol Pharmacol (2015) 0.83
Discovery of a Potent Allosteric Kinase Modulator by Combining Computational and Synthetic Methods. Angew Chem Int Ed Engl (2015) 0.75
ON THE NATURE OF ALLOSTERIC TRANSITIONS: A PLAUSIBLE MODEL. J Mol Biol (1965) 46.35
Exploiting the PI3K/AKT pathway for cancer drug discovery. Nat Rev Drug Discov (2005) 11.46
Protein kinases--the major drug targets of the twenty-first century? Nat Rev Drug Discov (2002) 7.38
Allosteric modulators of GPCRs: a novel approach for the treatment of CNS disorders. Nat Rev Drug Discov (2009) 6.69
MK-2206, an allosteric Akt inhibitor, enhances antitumor efficacy by standard chemotherapeutic agents or molecular targeted drugs in vitro and in vivo. Mol Cancer Ther (2010) 5.24
G protein-coupled receptor allosterism and complexing. Pharmacol Rev (2002) 5.01
Inhibitor hijacking of Akt activation. Nat Chem Biol (2009) 4.91
Metabotropic glutamate receptors: physiology, pharmacology, and disease. Annu Rev Pharmacol Toxicol (2010) 4.77
Crystal structure of the catalytic subunit of cAMP-dependent protein kinase complexed with MgATP and peptide inhibitor. Biochemistry (1993) 3.88
Identification and characterization of pleckstrin-homology-domain-dependent and isoenzyme-specific Akt inhibitors. Biochem J (2005) 3.58
Structural basis for control by phosphorylation. Chem Rev (2001) 3.53
Allosteric Akt (PKB) inhibitors: discovery and SAR of isozyme selective inhibitors. Bioorg Med Chem Lett (2005) 3.50
The Akt/PKB pathway: molecular target for cancer drug discovery. Oncogene (2005) 3.42
Seven transmembrane receptors as shapeshifting proteins: the impact of allosteric modulation and functional selectivity on new drug discovery. Pharmacol Rev (2010) 3.27
Protein phosphorylation in signaling--50 years and counting. Trends Biochem Sci (2005) 3.19
Allosteric binding sites on cell-surface receptors: novel targets for drug discovery. Nat Rev Drug Discov (2002) 2.85
A novel selective positive allosteric modulator of metabotropic glutamate receptor subtype 5 has in vivo activity and antipsychotic-like effects in rat behavioral models. J Pharmacol Exp Ther (2004) 2.83
A new benzodiazepine pharmacology. J Pharmacol Exp Ther (2002) 2.75
Design of isoform-selective phospholipase D inhibitors that modulate cancer cell invasiveness. Nat Chem Biol (2009) 2.72
Application of combinatorial chemistry science on modern drug discovery. J Comb Chem (2008) 2.64
Discovery of positive allosteric modulators for the metabotropic glutamate receptor subtype 5 from a series of N-(1,3-diphenyl-1H- pyrazol-5-yl)benzamides that potentiate receptor function in vivo. J Med Chem (2004) 2.46
Novel selective allosteric activator of the M1 muscarinic acetylcholine receptor regulates amyloid processing and produces antipsychotic-like activity in rats. J Neurosci (2008) 2.34
A family of highly selective allosteric modulators of the metabotropic glutamate receptor subtype 5. Mol Pharmacol (2003) 2.27
Tumor cell sensitization to apoptotic stimuli by selective inhibition of specific Akt/PKB family members. Mol Cancer Ther (2005) 2.23
A novel selective allosteric modulator potentiates the activity of native metabotropic glutamate receptor subtype 5 in rat forebrain. J Pharmacol Exp Ther (2004) 2.17
Challenges in the development of mGluR5 positive allosteric modulators: the discovery of CPPHA. Bioorg Med Chem Lett (2006) 2.17
Role of a novel PH-kinase domain interface in PKB/Akt regulation: structural mechanism for allosteric inhibition. PLoS Biol (2009) 2.15
Allosteric modulation of seven transmembrane spanning receptors: theory, practice, and opportunities for central nervous system drug discovery. J Med Chem (2012) 2.10
Allostery: an illustrated definition for the 'second secret of life'. Trends Biochem Sci (2008) 1.99
"Molecular switches" on mGluR allosteric ligands that modulate modes of pharmacology. Biochemistry (2011) 1.89
Selective activation of the M1 muscarinic acetylcholine receptor achieved by allosteric potentiation. Proc Natl Acad Sci U S A (2009) 1.87
Synthesis and SAR of a mGluR5 allosteric partial antagonist lead: unexpected modulation of pharmacology with slight structural modifications to a 5-(phenylethynyl)pyrimidine scaffold. Bioorg Med Chem Lett (2008) 1.78
Progress towards validating the NMDA receptor hypofunction hypothesis of schizophrenia. Curr Top Med Chem (2006) 1.77
G-protein-coupled receptors: from classical modes of modulation to allosteric mechanisms. ACS Chem Biol (2008) 1.76
AKT crystal structure and AKT-specific inhibitors. Oncogene (2005) 1.67
Phospholipase D: enzymology, functionality, and chemical modulation. Chem Rev (2011) 1.66
Pharmacodynamics of the type II calcimimetic compound cinacalcet HCl. J Pharmacol Exp Ther (2003) 1.63
Crystal structures of MEK1 binary and ternary complexes with nucleotides and inhibitors. Biochemistry (2009) 1.63
Recent advances in the design and development of novel negative allosteric modulators of mGlu(5). ACS Chem Neurosci (2011) 1.60
Optimization of halopemide for phospholipase D2 inhibition. Bioorg Med Chem Lett (2007) 1.58
Discovery of the first highly M5-preferring muscarinic acetylcholine receptor ligand, an M5 positive allosteric modulator derived from a series of 5-trifluoromethoxy N-benzyl isatins. J Med Chem (2009) 1.57
Strategies for the selective regulation of kinases with allosteric modulators: exploiting exclusive structural features. ACS Chem Biol (2012) 1.55
Discovery and characterization of novel subtype-selective allosteric agonists for the investigation of M(1) receptor function in the central nervous system. ACS Chem Neurosci (2010) 1.52
Opportunities and challenges in the discovery of allosteric modulators of GPCRs for treating CNS disorders. Nat Rev Drug Discov (2014) 1.51
Structure of class C GPCR metabotropic glutamate receptor 5 transmembrane domain. Nature (2014) 1.48
Progress toward positive allosteric modulators of the metabotropic glutamate receptor subtype 5 (mGluR5). ACS Chem Neurosci (2011) 1.44
The Akt/PKB family of protein kinases: a review of small molecule inhibitors and progress towards target validation. Curr Top Med Chem (2005) 1.37
Chemical lead optimization of a pan Gq mAChR M1, M3, M5 positive allosteric modulator (PAM) lead. Part II: development of a potent and highly selective M1 PAM. Bioorg Med Chem Lett (2010) 1.37
'7TM receptor allostery: putting numbers to shapeshifting proteins. Trends Pharmacol Sci (2009) 1.32
Targeting the phosphatidylinositol-3 kinase/Akt pathway for the treatment of cancer. Curr Opin Investig Drugs (2005) 1.31
The Akt/PKB family of protein kinases: a review of small molecule inhibitors and progress towards target validation: a 2009 update. Curr Top Med Chem (2010) 1.29
Design and synthesis of isoform-selective phospholipase D (PLD) inhibitors. Part I: Impact of alternative halogenated privileged structures for PLD1 specificity. Bioorg Med Chem Lett (2009) 1.28
Antipsychotic drug-like effects of the selective M4 muscarinic acetylcholine receptor positive allosteric modulator VU0152100. Neuropsychopharmacology (2014) 1.25
Unique signaling profiles of positive allosteric modulators of metabotropic glutamate receptor subtype 5 determine differences in in vivo activity. Biol Psychiatry (2012) 1.22
Discovery of a potential allosteric ligand binding site in CDK2. ACS Chem Biol (2011) 1.15
Investigating metabotropic glutamate receptor 5 allosteric modulator cooperativity, affinity, and agonism: enriching structure-function studies and structure-activity relationships. Mol Pharmacol (2012) 1.15
Xanomeline and the antipsychotic potential of muscarinic receptor subtype selective agonists. CNS Drug Rev (2003) 1.13
Novel allosteric agonists of M1 muscarinic acetylcholine receptors induce brain region-specific responses that correspond with behavioral effects in animal models. J Neurosci (2012) 1.13
Maraviroc, a chemokine CCR5 receptor antagonist for the treatment of HIV infection and AIDS. Curr Opin Investig Drugs (2007) 1.12
Mechanism based neurotoxicity of mGlu5 positive allosteric modulators--development challenges for a promising novel antipsychotic target. Neuropharmacology (2013) 1.10
Discovery of (R)-(2-fluoro-4-((-4-methoxyphenyl)ethynyl)phenyl) (3-hydroxypiperidin-1-yl)methanone (ML337), an mGlu3 selective and CNS penetrant negative allosteric modulator (NAM). J Med Chem (2013) 1.10
Chemical modulation of mutant mGlu1 receptors derived from deleterious GRM1 mutations found in schizophrenics. ACS Chem Biol (2014) 1.09
Re-exploration of the PHCCC Scaffold: Discovery of Improved Positive Allosteric Modulators of mGluR4. ACS Chem Neurosci (2010) 1.07
Selective activation of M4 muscarinic acetylcholine receptors reverses MK-801-induced behavioral impairments and enhances associative learning in rodents. ACS Chem Neurosci (2014) 1.06
Biotransformation of a novel positive allosteric modulator of metabotropic glutamate receptor subtype 5 contributes to seizure-like adverse events in rats involving a receptor agonism-dependent mechanism. Drug Metab Dispos (2013) 1.04
Drugs for allosteric sites on receptors. Annu Rev Pharmacol Toxicol (2013) 1.04
Development of a novel, CNS-penetrant, metabotropic glutamate receptor 3 (mGlu3) NAM probe (ML289) derived from a closely related mGlu5 PAM. Bioorg Med Chem Lett (2012) 1.03
Allosteric regulation of protein kinase PKCζ by the N-terminal C1 domain and small compounds to the PIF-pocket. Chem Biol (2011) 1.03
Targeting selective activation of M(1) for the treatment of Alzheimer's disease: further chemical optimization and pharmacological characterization of the M(1) positive allosteric modulator ML169. ACS Chem Neurosci (2012) 1.01
Chemical switch of a metabotropic glutamate receptor 2 silent allosteric modulator into dual metabotropic glutamate receptor 2/3 negative/positive allosteric modulators. J Med Chem (2010) 1.00
Phospholipase D facilitates efficient entry of influenza virus, allowing escape from innate immune inhibition. J Biol Chem (2014) 0.97
Pharmacological enhancement of mGlu1 metabotropic glutamate receptors causes a prolonged symptomatic benefit in a mouse model of spinocerebellar ataxia type 1. Mol Brain (2013) 0.96
Phospholipase D2 mediates survival signaling through direct regulation of Akt in glioblastoma cells. J Biol Chem (2013) 0.95
Development of dual PLD1/2 and PLD2 selective inhibitors from a common 1,3,8-Triazaspiro[4.5]decane Core: discovery of Ml298 and Ml299 that decrease invasive migration in U87-MG glioblastoma cells. J Med Chem (2013) 0.95
Chemical modification of the M(1) agonist VU0364572 reveals molecular switches in pharmacology and a bitopic binding mode. ACS Chem Neurosci (2012) 0.93
αC helix displacement as a general approach for allosteric modulation of protein kinases. Drug Discov Today (2012) 0.90
Structure, regulation, signaling, and targeting of abl kinases in cancer. Genes Cancer (2012) 0.90
The clinical significance of halopemide, a dopamine-blocker related to the butyrophenones. Neuropsychobiology (1984) 0.89
Substrate-selective inhibition of protein kinase PDK1 by small compounds that bind to the PIF-pocket allosteric docking site. Chem Biol (2012) 0.89
A novel class of succinimide-derived negative allosteric modulators of metabotropic glutamate receptor subtype 1 provides insight into a disconnect in activity between the rat and human receptors. ACS Chem Neurosci (2014) 0.88
Regulation of G protein-coupled receptors by allosteric ligands. ACS Chem Neurosci (2013) 0.87
Further exploration of M₁ allosteric agonists: subtle structural changes abolish M₁ allosteric agonism and result in pan-mAChR orthosteric antagonism. Bioorg Med Chem Lett (2012) 0.85
Synthesis and SAR of a novel metabotropic glutamate receptor 4 (mGlu4) antagonist: unexpected 'molecular switch' from a closely related mGlu4 positive allosteric modulator. Bioorg Med Chem Lett (2011) 0.83
Switching between agonists and antagonists at CRTh2 in a series of highly potent and selective biaryl phenoxyacetic acids. Bioorg Med Chem Lett (2011) 0.80
Pharmacoeconomics and the medicinal chemist. ACS Med Chem Lett (2014) 0.75