Publications
Histone deacetylase 6 inhibition restores leptin sensitivity and reduces obesity.
Işın Çakır , Colleen K. Hadley , Pauline Lining Pan , Rushita A. Bagchi , Masoud Ghamari-Langroudi , Danielle T. Porter , Qiuyu Wang , Michael J. Litt, Somnath Jana , Susan Hagen, Pil Lee, Andrew White, Jiandie D. Lin, Timothy A. McKinsey and Roger D. Cone, Nature Metabolism (2022), Published: 17 January 2022, https://doi.org/10.1038/s42255-021-00515-3
An erythroid-to-myeloid cell fate conversion is elicited by LSD1 inactivation.
Lei Yu, Greggory Myers, Chia-Jui Ku, Emily Schneider, Yu Wang, Sharon A. Singh, Natee Jearawiriyapaisarn, Andrew White, Takashi Moriguchi, Rami Khoriaty, Masayuki Yamamoto, Michael G. Rosenfeld, Julien Pedron, John H. Bushweller, Kim-Chew Lim, and James Douglas Engel; Blood. 2021 Nov 4;138(18):1691-1704. doi: 10.1182/blood.2021011682
Positive allosteric modulation of the mu-opioid receptor produces analgesia with reduced side effects.
Kandasamy R, Hillhouse TM, Livingston KE, Kochan KE, Meurice C, Eans SO, Li MH, White AD, Roques BP, McLaughlin JP, Ingram SL, Burford NT, Alt A, Traynor JR.Proc Natl Acad Sci U S A. 2021 Apr 20;118(16):e2000017118. doi: 10.1073/pnas.2000017118.PMID: 33846240
Generation of Highly Selective, Potent, and Covalent G Protein-Coupled Receptor Kinase 5 Inhibitors.
Rowlands RA, Chen Q, Bouley RA, Avramova LV, Tesmer JJG, White AD.J Med Chem. 2021 Jan 14;64(1):566-585. doi: 10.1021/acs.jmedchem.0c01522. Epub 2021 Jan 4.PMID: 33393767
Optimization of Eliglustat-Based Glucosylceramide Synthase Inhibitors as Substrate Reduction Therapy for Gaucher Disease Type 3.
Wilson MW, Shu L, Hinkovska-Galcheva V, Jin Y, Rajeswaran W, Abe A, Zhao T, Luo R, Wang L, Wen B, Liou B, Fannin V, Sun D, Sun Y, Shayman JA, Larsen SD.ACS Chem Neurosci. 2020 Oct 21;11(20):3464-3473. doi: 10.1021/acschemneuro.0c00558. Epub 2020 Oct 9.PMID: 33035424
Recent Progress in the Discovery and Development of 2-Nitroimidazooxazines and 6-Nitroimidazooxazoles to Treat Tuberculosis and Neglected Tropical Diseases.
Showalter HD.Molecules. 2020 Sep 10;25(18):4137. doi: 10.3390/molecules25184137.PMID: 32927749
Discovery and Optimization of Triazine Nitrile Inhibitors of Toxoplasma gondii Cathepsin L for the Potential Treatment of Chronic Toxoplasmosis in the CNS.
Zwicker JD, Smith D, Guerra AJ, Hitchens JR, Haug N, Vander Roest S, Lee P, Wen B, Sun D, Wang L, Keep RF, Xiang J, Carruthers VB, Larsen SD.ACS Chem Neurosci. 2020 Aug 19;11(16):2450-2463. doi: 10.1021/acschemneuro.9b00674. Epub 2020 Feb 18.PMID: 32027110
A New Paroxetine-Based GRK2 Inhibitor Reduces Internalization of the μ-Opioid Receptor.
Bouley RA, Weinberg ZY, Waldschmidt HV, Yen YC, Larsen SD, Puthenveedu MA, Tesmer JJG.Mol Pharmacol. 2020 Jun;97(6):392-401. doi: 10.1124/mol.119.118661. Epub 2020 Mar 31.PMID: 32234810
Synthesis and structure-activity relationships of thieno[2,3-d]pyrimidines as atypical protein kinase C inhibitors to control retinal vascular permeability and cytokine-induced edema.
Liu X, Wilson MW, Liu K, Lee P, Yeomans L, Hagen SE, Lin CM, Wen B, Sun D, White AD, Showalter HD, Antonetti DA.Bioorg Med Chem. 2020 Jun 1;28(11):115480. doi: 10.1016/j.bmc.2020.115480. Epub 2020 Apr 3.PMID: 32327351
Structure-Based Design of Selective, Covalent G Protein-Coupled Receptor Kinase 5 Inhibitors.
Rowlands RA, Cato MC, Waldschmidt HV, Bouley RA, Chen Q, Avramova L, Larsen SD, Tesmer JJG, White AD.ACS Med Chem Lett. 2019 Nov 12;10(12):1628-1634. doi: 10.1021/acsmedchemlett.9b00365. eCollection 2019 Dec 12.PMID: 31857838
Perturbation of ubiquitin homeostasis promotes macrophage oxidative defenses.
Charbonneau ME, Passalacqua KD, Hagen SE, Showalter HD, Wobus CE, O'Riordan MXD.Sci Rep. 2019 Jul 15;9(1):10245. doi: 10.1038/s41598-019-46526-9.PMID: 31308397
Altered Domain Structure of the Prion Protein Caused by Cu2+ Binding and Functionally Relevant Mutations: Analysis by Cross-Linking, MS/MS, and NMR.
McDonald AJ, Leon DR, Markham KA, Wu B, Heckendorf CF, Schilling K, Showalter HD, Andrews PC, McComb ME, Pushie MJ, Costello CE, Millhauser GL, Harris DA.Structure. 2019 Jun 4;27(6):907-922.e5. doi: 10.1016/j.str.2019.03.008. Epub 2019 Apr 4.PMID: 30956132
A concise synthesis of 3-substituted-7-amino-6-carboxyl-8-azachromones.
Gan X, Showalter HD.Tetrahedron Lett. 2019 Jul 25;60(30):2035-2037. doi: 10.1016/j.tetlet.2019.06.066. Epub 2019 Jun 29.PMID: 32831416
Synthesis of deuterium-labelled amlexanox and its metabolic stability against mouse, rat, and human microsomes.
Gan X, Wilson MW, Beyett TS, Wen B, Sun D, Larsen SD, Tesmer JJG, Saltiel AR, Showalter HD.J Labelled Comp Radiopharm. 2019 May 15;62(5):202-208. doi: 10.1002/jlcr.3716. Epub 2019 Apr 3.PMID: 30828860
5-Aryl-1,3,4-oxadiazol-2-ylthioalkanoic Acids: A Highly Potent New Class of Inhibitors of Rho/Myocardin-Related Transcription Factor (MRTF)/Serum Response Factor (SRF)-Mediated Gene Transcription as Potential Antifibrotic Agents for Scleroderma.
Kahl DJ, Hutchings KM, Lisabeth EM, Haak AJ, Leipprandt JR, Dexheimer T, Khanna D, Tsou PS, Campbell PL, Fox DA, Wen B, Sun D, Bailie M, Neubig RR, Larsen SD.J Med Chem. 2019 May 9;62(9):4350-4369. doi: 10.1021/acs.jmedchem.8b01772. Epub 2019 Apr 18.PMID: 30951312
Identification of Pirin as a Molecular Target of the CCG-1423/CCG-203971 Series of Antifibrotic and Antimetastatic Compounds.
Lisabeth EM, Kahl D, Gopallawa I, Haynes SE, Misek SA, Campbell PL, Dexheimer TS, Khanna D, Fox DA, Jin X, Martin BR, Larsen SD, Neubig RR.ACS Pharmacol Transl Sci. 2019 Apr 12;2(2):92-100. doi: 10.1021/acsptsci.8b00048. Epub 2019 Mar 18.PMID: 32039344
Revisiting the role of dihydroorotate dehydrogenase as a therapeutic target for cancer.
Madak JT, Bankhead A 3rd, Cuthbertson CR, Showalter HD, Neamati N.Pharmacol Ther. 2019 Mar;195:111-131. doi: 10.1016/j.pharmthera.2018.10.012. Epub 2018 Oct 19.PMID: 30347213
High-throughput screens for agonists of bone morphogenetic protein (BMP) signaling identify potent benzoxazole compounds.
Bradford STJ, Ranghini EJ, Grimley E, Lee PH, Dressler GR.J Biol Chem. 2019 Mar 1;294(9):3125-3136. doi: 10.1074/jbc.RA118.006817. Epub 2019 Jan 2.PMID: 30602563
Dual inhibition of Kif15 by oxindole and quinazolinedione chemical probes.
Dumas ME, Chen GY, Kendrick ND, Xu G, Larsen SD, Jana S, Waterson AG, Bauer JA, Hancock W, Sulikowski GA, Ohi R.Bioorg Med Chem Lett. 2019 Jan 15;29(2):148-154. doi: 10.1016/j.bmcl.2018.12.008. Epub 2018 Dec 4.PMID: 30528696
PPARγ-sparing thiazolidinediones as insulin sensitizers. Design, synthesis and selection of compounds for clinical development.
Tanis SP, Colca JR, Parker TT, Artman GD 3rd, Larsen SD, McDonald WG, Gadwood RC, Kletzien RF, Zeller JB, Lee PH, Adams WJ.Bioorg Med Chem. 2018 Dec 1;26(22):5870-5884. doi: 10.1016/j.bmc.2018.10.033. Epub 2018 Nov 2.PMID: 30429097
In vitro and in vivo delivery of a sustained release nanocarrier-based formulation of an MRTF/SRF inhibitor in conjunctival fibrosis.
Tagalakis AD, Madaan S, Larsen SD, Neubig RR, Khaw PT, Rodrigues I, Goyal S, Lim KS, Yu-Wai-Man C.J Nanobiotechnology. 2018 Nov 27;16(1):97. doi: 10.1186/s12951-018-0425-3.PMID: 30482196
Design, synthesis, and biological activity of substituted 2-amino-5-oxo-5H-chromeno[2,3-b]pyridine-3-carboxylic acid derivatives as inhibitors of the inflammatory kinases TBK1 and IKKε for the treatment of obesity.
Beyett TS, Gan X, Reilly SM, Gomez AV, Chang L, Tesmer JJG, Saltiel AR, Showalter HD.Bioorg Med Chem. 2018 Nov 1;26(20):5443-5461. doi: 10.1016/j.bmc.2018.09.020. Epub 2018 Sep 20.PMID: 30270002
Carboxylic Acid Derivatives of Amlexanox Display Enhanced Potency toward TBK1 and IKKε and Reveal Mechanisms for Selective Inhibition.
Beyett TS, Gan X, Reilly SM, Chang L, Gomez AV, Saltiel AR, Showalter HD, Tesmer JJG.Mol Pharmacol. 2018 Oct;94(4):1210-1219. doi: 10.1124/mol.118.112185. Epub 2018 Aug 6.PMID: 30082428
Synthesis of CID-cleavable protein crosslinking agents containing quaternary amines for structural mass spectrometry.
Hagen SE, Liu K, Jin Y, Piersimoni L, Andrews PC, Showalter HD.Org Biomol Chem. 2018 Sep 26;16(37):8245-8248. doi: 10.1039/c8ob00329g.PMID: 29537042
Optimization of dipeptidic inhibitors of cathepsin L for improved Toxoplasma gondii selectivity and CNS permeability.
Zwicker JD, Diaz NA, Guerra AJ, Kirchhoff PD, Wen B, Sun D, Carruthers VB, Larsen SD.Bioorg Med Chem Lett. 2018 Jun 1;28(10):1972-1980. doi: 10.1016/j.bmcl.2018.03.020. Epub 2018 Mar 9.PMID: 29650289
Utilizing a structure-based docking approach to develop potent G protein-coupled receptor kinase (GRK) 2 and 5 inhibitors.
Waldschmidt HV, Bouley R, Kirchhoff PD, Lee P, Tesmer JJG, Larsen SD.Bioorg Med Chem Lett. 2018 May 15;28(9):1507-1515. doi: 10.1016/j.bmcl.2018.03.082. Epub 2018 Mar 30.PMID: 29627263
Gedunin- and Khivorin-Derivatives Are Small-Molecule Partial Agonists for Adhesion G Protein-Coupled Receptors GPR56/ADGRG1 and GPR114/ADGRG5.
Stoveken HM, Larsen SD, Smrcka AV, Tall GG.Mol Pharmacol. 2018 May;93(5):477-488. doi: 10.1124/mol.117.111476. Epub 2018 Feb 23.PMID: 29476042
Minor Structural Variations of Small Molecules Tune Regulatory Activities toward Pathological Factors in Alzheimer's Disease.
Beck MW, Derrick JS, Suh JM, Kim M, Korshavn KJ, Kerr RA, Cho WJ, Larsen SD, Ruotolo BT, Ramamoorthy A, Lim MH.ChemMedChem. 2017 Nov 22;12(22):1828-1838. doi: 10.1002/cmdc.201700456. Epub 2017 Oct 9.PMID: 28990338
Structural Determinants Influencing the Potency and Selectivity of Indazole-Paroxetine Hybrid G Protein-Coupled Receptor Kinase 2 Inhibitors.
Bouley R, Waldschmidt HV, Cato MC, Cannavo A, Song J, Cheung JY, Yao XQ, Koch WJ, Larsen SD, Tesmer JJG.Mol Pharmacol. 2017 Dec;92(6):707-717. doi: 10.1124/mol.117.110130. Epub 2017 Oct 25.PMID: 29070696
Optimisation of Intestinal Fibrosis and Survival in the Mouse S. Typhimurium Model for Anti-fibrotic Drug Discovery and Preclinical Applications.
Johnson LA, Rodansky ES, Moons DS, Larsen SD, Neubig RR, Higgins PDR.J Crohns Colitis. 2017 Jun 1;11(6):724-736. doi: 10.1093/ecco-jcc/jjw210.PMID: 27986839
Pharmacokinetic optimitzation of CCG-203971: Novel inhibitors of the Rho/MRTF/SRF transcriptional pathway as potential antifibrotic therapeutics for systemic scleroderma.
Hutchings KM, Lisabeth EM, Rajeswaran W, Wilson MW, Sorenson RJ, Campbell PL, Ruth JH, Amin A, Tsou PS, Leipprandt JR, Olson SR, Wen B, Zhao T, Sun D, Khanna D, Fox DA, Neubig RR, Larsen SD.Bioorg Med Chem Lett. 2017 Apr 15;27(8):1744-1749. doi: 10.1016/j.bmcl.2017.02.070. Epub 2017 Mar 10.PMID: 28285914
Structure-Based Design of Highly Selective and Potent G Protein-Coupled Receptor Kinase 2 Inhibitors Based on Paroxetine.
Waldschmidt HV, Homan KT, Cato MC, Cruz-Rodríguez O, Cannavo A, Wilson MW, Song J, Cheung JY, Koch WJ, Tesmer JJ, Larsen SD.J Med Chem. 2017 Apr 13;60(7):3052-3069. doi: 10.1021/acs.jmedchem.7b00112. Epub 2017 Mar 29.PMID: 28323425
Local delivery of novel MRTF/SRF inhibitors prevents scar tissue formation in a preclinical model of fibrosis.
Yu-Wai-Man C, Spencer-Dene B, Lee RMH, Hutchings K, Lisabeth EM, Treisman R, Bailly M, Larsen SD, Neubig RR, Khaw PT.Sci Rep. 2017 Mar 31;7(1):518. doi: 10.1038/s41598-017-00212-w.PMID: 28364121
Pharmacological Inhibition of Myocardin-related Transcription Factor Pathway Blocks Lung Metastases of RhoC-Overexpressing Melanoma.
Haak AJ, Appleton KM, Lisabeth EM, Misek SA, Ji Y, Wade SM, Bell JL, Rockwell CE, Airik M, Krook MA, Larsen SD, Verhaegen M, Lawlor ER, Neubig RR.Mol Cancer Ther. 2017 Jan;16(1):193-204. doi: 10.1158/1535-7163.MCT-16-0482. Epub 2016 Nov 11.PMID: 27837031
