Search Results - "Kormos, Bethany L"

Discovery and Preclinical Profiling of 3‑[4-(Morpholin-4-yl)‑7H‑pyrrolo[2,3‑d]pyrimidin-5-yl]benzonitrile (PF-06447475), a Highly Potent, Selective, Brain Penetrant, and in Vivo Active LRRK2 Kinase Inhibitor by Henderson, Jaclyn L., Kormos, Bethany L., Hayward, Matthew M., Coffman, Karen J., Jasti, Jayasankar, Kurumbail, Ravi G., Wager, Travis T., Verhoest, Patrick R., Noell, G. Stephen, Chen, Yi, Needle, Elie, Berger, Zdenek, Steyn, Stefanus J., Houle, Christopher, Hirst, Warren D., Galatsis, Paul

“…Leucine rich repeat kinase 2 (LRRK2) has been genetically linked to Parkinson’s disease (PD) by genome-wide association studies (GWAS). The most common LRRK2…”
Get full text

An inverse agonist of orphan receptor GPR61 acts by a G protein-competitive allosteric mechanism by Lees, Joshua A., Dias, João M., Rajamohan, Francis, Fortin, Jean-Philippe, O’Connor, Rebecca, Kong, Jimmy X., Hughes, Emily A. G., Fisher, Ethan L., Tuttle, Jamison B., Lovett, Gabrielle, Kormos, Bethany L., Unwalla, Rayomand J., Zhang, Lei, Dechert Schmitt, Anne-Marie, Zhou, Dahui, Moran, Michael, Stevens, Kimberly A., Fennell, Kimberly F., Varghese, Alison E., Maxwell, Andrew, Cote, Emmaline E., Zhang, Yuan, Han, Seungil

“…GPR61 is an orphan GPCR related to biogenic amine receptors. Its association with phenotypes relating to appetite makes it of interest as a druggable target to…”
Get full text

A study of collective atomic fluctuations and cooperativity in the U1A–RNA complex based on molecular dynamics simulations by Kormos, Bethany L., Baranger, Anne M., Beveridge, David L.

“…Cooperative interactions play an important role in recognition and binding in macromolecular systems. In this study, we find that cross-correlated atomic…”
Get full text

Structure-inspired design of β-arrestin-biased ligands for aminergic GPCRs by McCorvy, John D, Butler, Kyle V, Kelly, Brendan, Rechsteiner, Katie, Karpiak, Joel, Betz, Robin M, Kormos, Bethany L, Shoichet, Brian K, Dror, Ron O, Jin, Jian, Roth, Bryan L

“…D2 dopamine receptor ligands biased for b-arrestin recruitment were developed based on a receptor homology model that identified conserved ligand contacts…”
Get full text

U1A protein-stem loop 2 RNA recognition: Prediction of structural differences from protein mutations by Kormos, Bethany L., Pieniazek, Susan N., Beveridge, David L., Baranger, Anne M.

“…Molecular dynamics (MD) simulations were carried out to compare the free and bound structures of wild type U1A protein with several Phe56 mutant U1A proteins…”
Get full text

Affinity and Specificity of Protein U1A-RNA Complex Formation Based on an Additive Component Free Energy Model by Kormos, Bethany L., Benitex, Yulia, Baranger, Anne M., Beveridge, David L.

“…An MM-GBSA computational protocol was used to investigate wild-type U1A-RNA and F56 U1A mutant experimental binding free energies. The trend in mutant binding…”
Get full text

NMR spectroscopy: the swiss army knife of drug discovery by Horst, Reto, Farley, Kathleen A., Kormos, Bethany L., Withka, Jane M.

“…Nuclear magnetic resonance (NMR) spectroscopy has evolved into a powerful tool within drug discovery over the last two decades. While traditionally being used…”
Get full text

Application of the Bicyclo[1.1.1]pentane Motif as a Nonclassical Phenyl Ring Bioisostere in the Design of a Potent and Orally Active γ-Secretase Inhibitor by Stepan, Antonia F, Subramanyam, Chakrapani, Efremov, Ivan V, Dutra, Jason K, O’Sullivan, Theresa J, DiRico, Kenneth J, McDonald, W. Scott, Won, Annie, Dorff, Peter H, Nolan, Charles E, Becker, Stacey L, Pustilnik, Leslie R, Riddell, David R, Kauffman, Gregory W, Kormos, Bethany L, Zhang, Liming, Lu, Yasong, Capetta, Steven H, Green, Michael E, Karki, Kapil, Sibley, Evelyn, Atchison, Kevin P, Hallgren, Andrew J, Oborski, Christine E, Robshaw, Ashley E, Sneed, Blossom, O’Donnell, Christopher J

“…Replacement of the central, para-substituted fluorophenyl ring in the γ-secretase inhibitor 1 (BMS-708,163) with the bicyclo[1.1.1]­pentane motif led to the…”
Get full text

Characterization of the Dynamics of an Essential Helix in the U1A Protein by Time-Resolved Fluorescence Measurements by Anunciado, Divina, Agumeh, Michael, Kormos, Bethany L, Beveridge, David L, Knee, Joseph L, Baranger, Anne M

“…The RNA recognition motif (RRM), one of the most common RNA-binding domains, recognizes single-stranded RNA. A C-terminal helix that undergoes conformational…”
Get full text

Structural studies identify angiotensin II receptor blocker-like compounds as branched-chain ketoacid dehydrogenase kinase inhibitors by Liu, Shenping, Kormos, Bethany L., Knafels, John D., Sahasrabudhe, Parag V., Rosado, Amy, Sommese, Ruth F., Reyes, Allan R., Ward, Jessica, Roth Flach, Rachel J., Wang, Xiaochun, Buzon, Leanne M., Reese, Matthew R., Bhattacharya, Samit K., Omoto, Kiyoyuki, Filipski, Kevin J.

“…The mammalian mitochondrial branched-chain ketoacid dehydrogenase (BCKD) complex is a multienzyme complex involved in the catabolism of branched-chain amino…”
Get full text

Dopamine D3 receptor antagonist reveals a cryptic pocket in aminergic GPCRs by Ferruz, Noelia, Doerr, Stefan, Vanase-Frawley, Michelle A., Zou, Yaozhong, Chen, Xiaomin, Marr, Eric S., Nelson, Robin T., Kormos, Bethany L., Wager, Travis T., Hou, Xinjun, Villalobos, Anabella, Sciabola, Simone, De Fabritiis, Gianni

“…The recent increase in the number of X-ray crystal structures of G-protein coupled receptors (GPCRs) has been enabling for structure-based drug design (SBDD)…”
Get full text

Discovery of First Branched-Chain Ketoacid Dehydrogenase Kinase (BDK) Inhibitor Clinical Candidate PF-07328948 by Filipski, Kevin J., Martinez-Alsina, Luis A., Reese, Matthew R., Evrard, Edelweiss, Buzon, Leanne M., Cameron, Kimberly O., Zhang, Yuan, Coffman, Karen J., Bradow, James, Kormos, Bethany L., Liu, Shenping, Knafels, John D., Sahasrabudhe, Parag V., Chen, Jie, Kalgutkar, Amit S., Bessire, Andrew J., Orozco, Christine C., Balesano, Amanda, Cerny, Matthew A., Bollinger, Eliza, Reyes, Allan R., Laforest, Brigitte, Rosado, Amy, Williams, George, Marshall, Mackenzie, Tam Neale, Kelly, Chen, Xian, Hirenallur-Shanthappa, Dinesh, Stansfield, John C., Groarke, John, Qiu, Ruolun, Karas, Spinel, Roth Flach, Rachel J., Esler, William P.

“…Inhibition of branched-chain ketoacid dehydrogenase kinase (BDK or BCKDK), a negative regulator of branched-chain amino acid (BCAA) metabolism, is hypothesized…”
Get full text

Small molecule branched-chain ketoacid dehydrogenase kinase (BDK) inhibitors with opposing effects on BDK protein levels by Roth Flach, Rachel J., Bollinger, Eliza, Reyes, Allan R., Laforest, Brigitte, Kormos, Bethany L., Liu, Shenping, Reese, Matthew R., Martinez Alsina, Luis A., Buzon, Leanne, Zhang, Yuan, Bechle, Bruce, Rosado, Amy, Sahasrabudhe, Parag V., Knafels, John, Bhattacharya, Samit K., Omoto, Kiyoyuki, Stansfield, John C., Hurley, Liam D., Song, LouJin, Luo, Lina, Breitkopf, Susanne B., Monetti, Mara, Cunio, Teresa, Tierney, Brendan, Geoly, Frank J., Delmore, Jake, Siddall, C. Parker, Xue, Liang, Yip, Ka N., Kalgutkar, Amit S., Miller, Russell A., Zhang, Bei B., Filipski, Kevin J.

“…Branched chain amino acid (BCAA) catabolic impairments have been implicated in several diseases. Branched chain ketoacid dehydrogenase (BCKDH) controls the…”
Get full text

Improving the Odds of Success in Drug Discovery: Choosing the Best Compounds for in Vivo Toxicology Studies by Wager, Travis T, Kormos, Bethany L, Brady, Joseph T, Will, Yvonne, Aleo, Michael D, Stedman, Donald B, Kuhn, Max, Chandrasekaran, Ramalakshmi Y

“…A set of molecules that advanced into exploratory animal toxicology studies (two species) was examined to determine what properties contributed to success in…”
Get full text

Identification of a Potent, Highly Selective, and Brain Penetrant Phosphodiesterase 2A Inhibitor Clinical Candidate by Helal, Christopher J, Arnold, Eric, Boyden, Tracey, Chang, Cheng, Chappie, Thomas A, Fisher, Ethan, Hajos, Mihaly, Harms, John F, Hoffman, William E, Humphrey, John M, Pandit, Jayvardhan, Kang, Zhijun, Kleiman, Robin J, Kormos, Bethany L, Lee, Che-Wah, Lu, Jiemin, Maklad, Noha, McDowell, Laura, McGinnis, Dina, O’Connor, Rebecca E, O’Donnell, Christopher J, Ogden, Adam, Piotrowski, Mary, Schmidt, Christopher J, Seymour, Patricia A, Ueno, Hirokazu, Vansell, Nichole, Verhoest, Patrick R, Yang, Edward X

“…Computational modeling was used to direct the synthesis of analogs of previously reported phosphodiesterase 2A (PDE2A) inhibitor 1 with an imidazotriazine core…”
Get full text

Pseudo-Two-Dimensional Structures (HXYH)3n2H6n (XY = GaN, SiC, GeC, SiSi, or GeGe; n = 1−3):  Density Functional Characterization of Structures and Energetics by KORMOS, Bethany L., CRAMER, Christopher J., GLADFELTER, Wayne L.

“…Hybrid density functional calculations with effective core potential basis sets are performed for monomeric group 13/15 and group 14/14 analogues of…”
Get full text

Identification of Phosphorylation Consensus Sequences and Endogenous Neuronal Substrates of the Psychiatric Risk Kinase TNIK by Wang, Qi, Amato, Stephen P, Rubitski, David M, Hayward, Matthew M, Kormos, Bethany L, Verhoest, Patrick R, Xu, Lan, Brandon, Nicholas J, Ehlers, Michael D

“…Traf2- and Nck-interacting kinase (TNIK) is a serine/threonine kinase highly expressed in the brain and enriched in the postsynaptic density of glutamatergic…”
Get more information

Application of Structure-Based Design and Parallel Chemistry to Identify a Potent, Selective, and Brain Penetrant Phosphodiesterase 2A Inhibitor by Helal, Christopher J, Arnold, Eric P, Boyden, Tracey L, Chang, Cheng, Chappie, Thomas A, Fennell, Kimberly F, Forman, Michael D, Hajos, Mihaly, Harms, John F, Hoffman, William E, Humphrey, John M, Kang, Zhijun, Kleiman, Robin J, Kormos, Bethany L, Lee, Che-Wah, Lu, Jiemin, Maklad, Noha, McDowell, Laura, Mente, Scot, O’Connor, Rebecca E, Pandit, Jayvardhan, Piotrowski, Mary, Schmidt, Anne W, Schmidt, Christopher J, Ueno, Hirokazu, Verhoest, Patrick R, Yang, Edward X

“…Phosphodiesterase 2A (PDE2A) inhibitors have been reported to demonstrate in vivo activity in preclinical models of cognition. To more fully explore the…”
Get full text

Author Correction: Dopamine D3 receptor antagonist reveals a cryptic pocket in aminergic GPCRs by Ferruz, Noelia, Doerr, Stefan, Vanase-Frawley, Michelle A., Zou, Yaozhong, Chen, Xiaomin, Marr, Eric S., Nelson, Robin T., Kormos, Bethany L., Wager, Travis T., Hou, Xinjun, Villalobos, Anabella, Sciabola, Simone, De Fabritiis, Gianni

“…A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper…”
Get full text

Kinase domain inhibition of leucine rich repeat kinase 2 (LRRK2) using a [1,2,4]triazolo[4,3-b]pyridazine scaffold by Galatsis, Paul, Henderson, Jaclyn L., Kormos, Bethany L., Han, Seungil, Kurumbail, Ravi G., Wager, Travis T., Verhoest, Patrick R., Noell, G. Stephen, Chen, Yi, Needle, Elie, Berger, Zdenek, Steyn, Stefanus J., Houle, Christopher, Hirst, Warren D.

“…Leucine rich repeat kinase 2 (LRRK2) has been genetically linked to Parkinson’s disease (PD). The most common mutant, G2019S, increases kinase activity, thus…”
Get full text