Search Results - "STEYN, Stefanus J"

Predicting Clearance Mechanism in Drug Discovery: Extended Clearance Classification System (ECCS) by Varma, Manthena V., Steyn, Stefanus J., Allerton, Charlotte, El-Kattan, Ayman F.

“…Early prediction of clearance mechanisms allows for the rapid progression of drug discovery and development programs, and facilitates risk assessment of the…”
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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…”
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Physicochemical Space for Optimum Oral Bioavailability: Contribution of Human Intestinal Absorption and First-Pass Elimination by Varma, Manthena V. S, Obach, R. Scott, Rotter, Charles, Miller, Howard R, Chang, George, Steyn, Stefanus J, El-Kattan, Ayman, Troutman, Matthew D

“…Oral bioavailability (F) is a product of fraction absorbed (Fa), fraction escaping gut-wall elimination (Fg), and fraction escaping hepatic elimination (Fh)…”
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A perspective on the prediction of drug pharmacokinetics and disposition in drug research and development by Di, Li, Feng, Bo, Goosen, Theunis C, Lai, Yurong, Steyn, Stefanus J, Varma, Manthena V, Obach, R Scott

“…Prediction of human pharmacokinetics of new drugs, as well as other disposition attributes, has become a routine practice in drug research and development…”
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Lack of Effect of Sodium Benzoate at Reported Clinical Therapeutic Concentration on d‑Alanine Metabolism in Dogs by Popiolek, Michael, Tierney, Brendan, Steyn, Stefanus J, DeVivo, Michael

“…Cognitive decline and psychosis have been hypothesized to be mediated by N-methyl-d-aspartate receptor (NMDAR) hypofunction. Consistent with this hypothesis,…”
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Discovery, SAR, and Pharmacokinetics of a Novel 3-Hydroxyquinolin-2(1H)-one Series of Potent d-Amino Acid Oxidase (DAAO) Inhibitors by Duplantier, Allen J, Becker, Stacey L, Bohanon, Michael J, Borzilleri, Kris A, Chrunyk, Boris A, Downs, James T, Hu, Lain-Yen, El-Kattan, Ayman, James, Larry C, Liu, Shenping, Lu, Jiemin, Maklad, Noha, Mansour, Mahmoud N, Mente, Scot, Piotrowski, Mary A, Sakya, Subas M, Sheehan, Susan, Steyn, Stefanus J, Strick, Christine A, Williams, Victoria A, Zhang, Lei

“…3-Hydroxyquinolin-2(1H)-one (2) was discovered by high throughput screening in a functional assay to be a potent inhibitor of human DAAO, and its binding…”
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Striatal, Hippocampal, and Cortical Networks Are Differentially Responsive to the M4- and M1-Muscarinic Acetylcholine Receptor Mediated Effects of Xanomeline by Thorn, Catherine A, Moon, Joshua, Bourbonais, Clinton A, Harms, John, Edgerton, Jeremy R, Stark, Eda, Steyn, Stefanus J, Butter, Christopher R, Lazzaro, John T, O’Connor, Rebecca E, Popiolek, Michael

“…Preclinical and clinical data suggest that muscarinic acetyl­choline receptor activation may be therapeutically beneficial for the treatment of schizophrenia…”
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Modulation of NMDA receptor function by inhibition of d-amino acid oxidase in rodent brain by Strick, Christine A., Li, Cheryl, Scott, Liam, Harvey, Brian, Hajós, Mihály, Steyn, Stefanus J., Piotrowski, Mary A., James, Larry C., Downs, James T., Rago, Brian, Becker, Stacey L., El-Kattan, Ayman, Xu, Youfen, Ganong, Alan H., Tingley, F. David, Ramirez, Andres D., Seymour, Patricia A., Guanowsky, Victor, Majchrzak, Mark J., Fox, Carol B., Schmidt, Christopher J., Duplantier, Allen J.

“…Observations that N-Methyl- d-Aspartate (NMDA) antagonists produce symptoms in humans that are similar to those seen in schizophrenia have led to the current…”
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Leucine-rich Repeat Kinase 2 (LRRK2) Pharmacological Inhibition Abates α-Synuclein Gene-induced Neurodegeneration by Daher, João P.L., Abdelmotilib, Hisham A., Hu, Xianzhen, Volpicelli-Daley, Laura A., Moehle, Mark S., Fraser, Kyle B., Needle, Elie, Chen, Yi, Steyn, Stefanus J., Galatsis, Paul, Hirst, Warren D., West, Andrew B.

“…Therapeutic approaches to slow or block the progression of Parkinson disease (PD) do not exist. Genetic and biochemical studies implicate α-synuclein and…”
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Comparative Study of Dermal Pharmacokinetics Between Topical Drugs Using Open Flow Microperfusion in a Pig Model by Bodenlenz, Manfred, Yeoh, Thean, Berstein, Gabriel, Mathew, Shibin, Shah, Jaymin, Banfield, Christopher, Hollingshead, Brett, Steyn, Stefanus J., Osgood, Sarah M., Beaumont, Kevin, Kainz, Sonja, Holeček, Christian, Trausinger, Gert, Raml, Reingard, Birngruber, Thomas

“…Purpose Accurate methods to determine dermal pharmacokinetics are important to increase the rate of clinical success in topical drug development. We…”
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Correction: Comparative Study of Dermal Pharmacokinetics Between Topical Drugs Using Open Flow Microperfusion in a Pig Model by Bodenlenz, Manfred, Yeoh, Thean, Berstein, Gabriel, Mathew, Shibin, Shah, Jaymin, Banfield, Christopher, Hollingshead, Brett, Steyn, Stefanus J., Osgood, Sarah M., Beaumont, Kevin, Kainz, Sonja, Holeček, Christian, Trausinger, Gert, Raml, Reingard, Birngruber, Thomas

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Imaging Leucine-Rich Repeat Kinase 2 In Vivo with 18F‑Labeled Positron Emission Tomography Ligand by Chen, Zhen, Chen, Jiahui, Chen, Laigao, Yoo, Chi-Hyeon, Rong, Jian, Fu, Hualong, Shao, Tuo, Coffman, Karen, Steyn, Stefanus J., Davenport, April T., Daunais, James B., Haider, Ahmed, Collier, Lee, Josephson, Lee, Wey, Hsiao-Ying, Zhang, Lei, Liang, Steven H.

“…Leucine-rich repeat kinase 2 (LRRK2) has been demonstrated to be closely involved in the pathogenesis of Parkinson’s disease (PD), and pharmacological blockade…”
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Cytochrome-P450-Mediated Drug–Drug Interactions of Substrate Drugs: Assessing Clinical Risk Based on Molecular Properties and an Extended Clearance Classification System by Steyn, Stefanus J, Varma, Manthena V. S

“…Cytochrome-P450 (P450) isoforms are major drug-metabolizing enzymes implicated in the clearance and drug–drug interactions (DDIs) of diverse small-molecule…”
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Design and Synthesis of Clinical Candidate PF-06852231 (CVL-231): A Brain Penetrant, Selective, Positive Allosteric Modulator of the M4 Muscarinic Acetylcholine Receptor by Butler, Christopher R., Popiolek, Michael, McAllister, Laura A., LaChapelle, Erik A., Kramer, Melissa, Beck, Elizabeth M., Mente, Scot, Brodney, Michael A., Brown, Matthew, Gilbert, Adam, Helal, Chris, Ogilvie, Kevin, Starr, Jeremy, Uccello, Daniel, Grimwood, Sarah, Edgerton, Jeremy, Garst-Orozco, Jonathan, Kozak, Rouba, Lotarski, Susan, Rossi, Amie, Smith, Deborah, O’Connor, Rebecca, Lazzaro, John, Steppan, Claire, Steyn, Stefanus J.

“…Selective activation of the M4 muscarinic acetylcholine receptor subtype offers a novel strategy for the treatment of psychosis in multiple neurological…”
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Design and Synthesis of Clinical Candidate PF-06852231 (CVL-231): A Brain Penetrant, Selective, Positive Allosteric Modulator of the M 4 Muscarinic Acetylcholine Receptor by Butler, Christopher R, Popiolek, Michael, McAllister, Laura A, LaChapelle, Erik A, Kramer, Melissa, Beck, Elizabeth M, Mente, Scot, Brodney, Michael A, Brown, Matthew, Gilbert, Adam, Helal, Chris, Ogilvie, Kevin, Starr, Jeremy, Uccello, Daniel, Grimwood, Sarah, Edgerton, Jeremy, Garst-Orozko, Jonathan, Kozak, Rouba, Lotarski, Susan, Rossi, Amie, Smith, Deborah, O'Connor, Rebecca, Lazzaro, John, Steppan, Claire, Steyn, Stefanus J

“…Selective activation of the M muscarinic acetylcholine receptor subtype offers a novel strategy for the treatment of psychosis in multiple neurological…”
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Discovery of the Potent and Selective M1 PAM-Agonist N‑[(3R,4S)‑3-Hydroxytetrahydro‑2H‑pyran-4-yl]-5-methyl-4-[4-(1,3-thiazol-4-yl)benzyl]­pyridine-2-carboxamide (PF-06767832): Evaluation of Efficacy and Cholinergic Side Effects by Davoren, Jennifer E, Lee, Che-Wah, Garnsey, Michelle, Brodney, Michael A, Cordes, Jason, Dlugolenski, Keith, Edgerton, Jeremy R, Harris, Anthony R, Helal, Christopher J, Jenkinson, Stephen, Kauffman, Gregory W, Kenakin, Terrence P, Lazzaro, John T, Lotarski, Susan M, Mao, Yuxia, Nason, Deane M, Northcott, Carrie, Nottebaum, Lisa, O’Neil, Steven V, Pettersen, Betty, Popiolek, Michael, Reinhart, Veronica, Salomon-Ferrer, Romelia, Steyn, Stefanus J, Webb, Damien, Zhang, Lei, Grimwood, Sarah

“…It is hypothesized that selective muscarinic M1 subtype activation could be a strategy to provide cognitive benefits to schizophrenia and Alzheimer’s disease…”
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Imaging Leucine-Rich Repeat Kinase 2 In Vivo with 18 F-Labeled Positron Emission Tomography Ligand by Chen, Zhen, Chen, Jiahui, Chen, Laigao, Yoo, Chi-Hyeon, Rong, Jian, Fu, Hualong, Shao, Tuo, Coffman, Karen, Steyn, Stefanus J, Davenport, April T, Daunais, James B, Haider, Ahmed, Collier, Lee, Josephson, Lee, Wey, Hsiao-Ying, Zhang, Lei, Liang, Steven H

“…Leucine-rich repeat kinase 2 (LRRK2) has been demonstrated to be closely involved in the pathogenesis of Parkinson's disease (PD), and pharmacological blockade…”
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pH-Dependent Solubility and Permeability Criteria for Provisional Biopharmaceutics Classification (BCS and BDDCS) in Early Drug Discovery by Varma, Manthena V, Gardner, Iain, Steyn, Stefanus J, Nkansah, Paul, Rotter, Charles J, Whitney-Pickett, Carrie, Zhang, Hui, Di, Li, Cram, Michael, Fenner, Katherine S, El-Kattan, Ayman F

“…The Biopharmaceutics Classification System (BCS) is a scientific framework that provides a basis for predicting the oral absorption of drugs. These concepts…”
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Design and Synthesis of γ- and δ‑Lactam M1 Positive Allosteric Modulators (PAMs): Convulsion and Cholinergic Toxicity of an M1‑Selective PAM with Weak Agonist Activity by Davoren, Jennifer E, Garnsey, Michelle, Pettersen, Betty, Brodney, Michael A, Edgerton, Jeremy R, Fortin, Jean-Philippe, Grimwood, Sarah, Harris, Anthony R, Jenkinson, Stephen, Kenakin, Terry, Lazzaro, John T, Lee, Che-Wah, Lotarski, Susan M, Nottebaum, Lisa, O’Neil, Steven V, Popiolek, Michael, Ramsey, Simeon, Steyn, Stefanus J, Thorn, Catherine A, Zhang, Lei, Webb, Damien

“…Recent data demonstrated that activation of the muscarinic M1 receptor by a subtype-selective positive allosteric modulator (PAM) contributes to the…”
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Discovery of Clinical Candidate PF-06648671: A Potent γ‑Secretase Modulator for the Treatment of Alzheimer’s Disease by Pettersson, Martin, Johnson, Douglas S., Humphrey, John M., am Ende, Christopher W., Butler, Todd W., Dorff, Peter H., Efremov, Ivan V., Evrard, Edelweiss, Green, Michael E., Helal, Christopher J., Kauffman, Gregory W., Mullins, Patrick B., Navaratnam, Thayalan, O’Donnell, Christopher J., O’Sullivan, Theresa J., Patel, Nandini C., Stepan, Antonia F., Stiff, Cory M., Subramanyam, Chakrapani, Trapa, Patrick, Tran, Tuan P., Vetelino, Beth Cooper, Yang, Eddie, Xie, Longfei, Pustilnik, Leslie R., Steyn, Stefanus J., Wood, Kathleen M., Bales, Kelly R., Hajos-Korcsok, Eva, Verhoest, Patrick R.

“…Herein, we describe the design and synthesis of γ-secretase modulator (GSM) clinical candidate PF-06648671 (22) for the treatment of Alzheimer’s disease. A key…”
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