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Page 1
Discovery, Optimization, and Biological Characterization of 2,3,6-Trisubstituted Pyridine-Containing M4 Positive Allosteric Modulators.
Schubert JW, Harrison ST, Mulhearn J, Gomez R, Tynebor R, Jones K, Bunda J, Hanney B, Wai JM, Cox C, McCauley JA, Sanders JM, Magliaro B, O'Brien J, Pajkovic N, Huszar Agrapides SL, Taylor A, Gotter A, Smith SM, Uslaner J, Browne S, Risso S, Egbertson M. Schubert JW, et al. ChemMedChem. 2019 May 6;14(9):943-951. doi: 10.1002/cmdc.201900088. Epub 2019 Mar 28. ChemMedChem. 2019. PMID: 30920765
Further optimization led to identification of the potent, receptor-subtype-selective, brain-penetrant tool compound 24 (7-[3-[1-[(1-fluorocyclopentyl)methyl]pyrazol-4-yl]-6-methyl-2-pyridyl]-3-methoxycinnoline). ...
Further optimization led to identification of the potent, receptor-subtype-selective, brain-penetrant tool compound 24 (7-[3-[1-[(1-f …
A novel glucosylceramide synthase inhibitor attenuates alpha synuclein pathology and lysosomal dysfunction in preclinical models of synucleinopathy.
Cosden M, Jinn S, Yao L, Gretzula CA, Kandebo M, Toolan D, Hatcher NG, Ma L, Lemaire W, Adam GC, Burlein C, Minnick C, Flick R, Watt ML, Mulhearn J, Fraley M, Drolet RE, Marcus JN, Smith SM. Cosden M, et al. Neurobiol Dis. 2021 Nov;159:105507. doi: 10.1016/j.nbd.2021.105507. Epub 2021 Sep 9. Neurobiol Dis. 2021. PMID: 34509608 Free article.
In vivo studies revealed BZ1 had pharmacological activity and reduced glycosphingolipids in the mouse brain to a similar extent observed in neuronal cultures. These data support the hypothesis that reduction of glycosphingolipids through GCS inhibition may impact progressi …
In vivo studies revealed BZ1 had pharmacological activity and reduced glycosphingolipids in the mouse brain to a similar extent obser …
Characterization of non-nitrocatechol pan and isoform specific catechol-O-methyltransferase inhibitors and substrates.
Robinson RG, Smith SM, Wolkenberg SE, Kandebo M, Yao L, Gibson CR, Harrison ST, Polsky-Fisher S, Barrow JC, Manley PJ, Mulhearn JJ, Nanda KK, Schubert JW, Trotter BW, Zhao Z, Sanders JM, Smith RF, McLoughlin D, Sharma S, Hall DL, Walker TL, Kershner JL, Bhandari N, Hutson PH, Sachs NA. Robinson RG, et al. ACS Chem Neurosci. 2012 Feb 15;3(2):129-40. doi: 10.1021/cn200109w. Epub 2011 Nov 14. ACS Chem Neurosci. 2012. PMID: 22860182 Free PMC article.
Since membrane bound COMT (MB-COMT) is the predominant isoform in human brain, a high throughput screen (HTS) to identify novel MB-COMT specific inhibitors was completed. ...
Since membrane bound COMT (MB-COMT) is the predominant isoform in human brain, a high throughput screen (HTS) to identify novel MB-CO …
[18F]Fluoroazabenzoxazoles as potential amyloid plaque PET tracers: synthesis and in vivo evaluation in rhesus monkey.
Hostetler ED, Sanabria-Bohórquez S, Fan H, Zeng Z, Gammage L, Miller P, O'Malley S, Connolly B, Mulhearn J, Harrison ST, Wolkenberg SE, Barrow JC, Williams DL Jr, Hargreaves RJ, Sur C, Cook JJ. Hostetler ED, et al. Nucl Med Biol. 2011 Nov;38(8):1193-203. doi: 10.1016/j.nucmedbio.2011.04.004. Epub 2011 Jul 7. Nucl Med Biol. 2011. PMID: 21741254
METHODS: Ligands were evaluated for their in vitro binding to human amyloid plaques, lipophilicity and predicted blood-brain barrier permeability. Candidates with favorable in vitro properties were radiolabeled with (18)F and evaluated in vivo. ...
METHODS: Ligands were evaluated for their in vitro binding to human amyloid plaques, lipophilicity and predicted blood-brain barrier …
Discovery of [11C]MK-6884: A Positron Emission Tomography (PET) Imaging Agent for the Study of M4Muscarinic Receptor Positive Allosteric Modulators (PAMs) in Neurodegenerative Diseases.
Tong L, Li W, Lo MM, Gao X, Wai JM, Rudd M, Tellers D, Joshi A, Zeng Z, Miller P, Salinas C, Riffel K, Haley H, Purcell M, Holahan M, Gantert L, Schubert JW, Jones K, Mulhearn J, Egbertson M, Meng Z, Hanney B, Gomez R, Harrison ST, McQuade P, Bueters T, Uslaner J, Morrow J, Thomson F, Kong J, Liao J, Selyutin O, Bao J, Hastings NB, Agrawal S, Magliaro BC, Monsma FJ Jr, Smith MD, Risso S, Hesk D, Hostetler E, Mazzola R. Tong L, et al. J Med Chem. 2020 Mar 12;63(5):2411-2425. doi: 10.1021/acs.jmedchem.9b01406. Epub 2020 Mar 3. J Med Chem. 2020. PMID: 32101422 Free article.
We first demonstrated its feasibility by mapping the receptor distribution in mouse brain and confirming that a lead molecule 1 binds selectively to the receptor only in the presence of the orthosteric agonist carbachol. ...
We first demonstrated its feasibility by mapping the receptor distribution in mouse brain and confirming that a lead molecule 1 binds …
Safe and effective intravenous thrombolysis for acute ischemic stroke caused by left atrial myxoma.
Nagy CD, Levy M, Mulhearn TJ 4th, Shapland M, Sun H, Yuh DD, Cheung D, Chandra-Strobos N. Nagy CD, et al. J Stroke Cerebrovasc Dis. 2009 Sep-Oct;18(5):398-402. doi: 10.1016/j.jstrokecerebrovasdis.2008.11.012. J Stroke Cerebrovasc Dis. 2009. PMID: 19717026
Definitive treatment for primary and secondary stroke prevention is surgical resection. The role of thrombolysis in acute brain ischemia in patients with atrial myxoma is not defined. There are few data available regarding safety and efficacy of thrombolytic therapy in acu …
Definitive treatment for primary and secondary stroke prevention is surgical resection. The role of thrombolysis in acute brain ische …
Synthesis and Evaluation of 5-Fluoro-2-aryloxazolo[5,4-b]pyridines as β-Amyloid PET Ligands and Identification of MK-3328.
Harrison ST, Mulhearn J, Wolkenberg SE, Miller PJ, O'Malley SS, Zeng Z, Williams DL Jr, Hostetler ED, Sanabria-Bohórquez S, Gammage L, Fan H, Sur C, Culberson JC, Hargreaves RJ, Cook JJ, Hartman GD, Barrow JC. Harrison ST, et al. ACS Med Chem Lett. 2011 Apr 18;2(7):498-502. doi: 10.1021/ml200018n. eCollection 2011 Jul 14. ACS Med Chem Lett. 2011. PMID: 24900338 Free PMC article.
5-Fluoro-2-aryloxazolo[5,4-b]pyridines were synthesized and investigated as potential (18)F containing beta-amyloid PET ligands. In competition binding assays using human AD brain homogenates, compounds 14b, 16b, and 17b were identified as having favorable potency versus h …
5-Fluoro-2-aryloxazolo[5,4-b]pyridines were synthesized and investigated as potential (18)F containing beta-amyloid PET ligands. In competit …