Ion channels and transporters are membrane proteins selectively permeable to ions, small olecular nutrients and metabolites. These proteins are critical to a variety of biological processes and represent a large class of therapeutic targets. Bioactive small molecules are a key source for identification of life-altering Pharmaceuticals and life science discovery probes. Different from many protein classes, ion channels and transporters often require special instruments and unique experimental expertise in order to perform analyses. Thus, carrying out large-scale compound library screens for ion channels has posed a considerable challenge. Johns Hopkins ChemCORE is a fully operational, high throughput compound screening facility with a strong combination of scientific excellence, operational productivity, and ion channel expertise. Hence, the existing operation at Hopkins is ideally suited to contribute the production phase of the Molecular Libraries Probe Production Centers Network (MLPCN). We therefore propose to form the Johns Hopkins Ion Channel Center (JHICC) - """"""""Specialized Screening Center"""""""" JHICC will meet the following specific aims: (1) to screen large diverse molecular libraries of 300,000 or more compounds against each of thefive important ion channel/transporter targets assigned by NIH, (2) to actively collaborate with chemists in other network centers to maximize probe development and production, (3) to disseminate the resulting information to the public domain (PubChem), and (4) to perform Center-driven research projects with significant impact on molecular probe discovery and development. By maximizing its quality and productivity and by adhering to MLPCN governance mechanisms, JHICC will be a responsible and highly productive member of the MLPCN and NIH Roadmap Initiative.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54MH084691-03
Application #
7938066
Study Section
Special Emphasis Panel (ZRG1-IFCN-K (52))
Program Officer
Brady, Linda S
Project Start
2008-09-01
Project End
2014-05-31
Budget Start
2010-06-01
Budget End
2011-05-31
Support Year
3
Fiscal Year
2010
Total Cost
$3,594,925
Indirect Cost
Name
Johns Hopkins University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Agoulnik, Alexander I; Agoulnik, Irina U; Hu, Xin et al. (2017) Synthetic non-peptide low molecular weight agonists of the relaxin receptor 1. Br J Pharmacol 174:977-989
Wu, Ying; Zou, Beiyan; Liang, Lingli et al. (2017) Loperamide inhibits sodium channels to alleviate inflammatory hyperalgesia. Neuropharmacology 117:282-291
Qu, Chunrong; Ding, Mingmin; Zhu, Yingmin et al. (2017) Pyrazolopyrimidines as Potent Stimulators for Transient Receptor Potential Canonical 3/6/7 Channels. J Med Chem 60:4680-4692
Yu, Hai-bo; Zou, Bei-yan; Wang, Xiao-liang et al. (2016) Investigation of miscellaneous hERG inhibition in large diverse compound collection using automated patch-clamp assay. Acta Pharmacol Sin 37:111-23
Sun, Han; Luo, Liqun; Lal, Bachchu et al. (2016) A monoclonal antibody against KCNK9 K(+) channel extracellular domain inhibits tumour growth and metastasis. Nat Commun 7:10339
Peters, Christian J; Yu, Haibo; Tien, Jason et al. (2015) Four basic residues critical for the ion selectivity and pore blocker sensitivity of TMEM16A calcium-activated chloride channels. Proc Natl Acad Sci U S A 112:3547-52
Zhang, Hongkang; Zou, Beiyan; Du, Fang et al. (2015) Reporting sodium channel activity using calcium flux: pharmacological promiscuity of cardiac Nav1.5. Mol Pharmacol 87:207-17
Wen, Wandong; Wang, Yan; Li, Zhe et al. (2015) Discovery and characterization of 2-(cyclopropanesulfonamido)-N-(2-ethoxyphenyl)benzamide, ML382: a potent and selective positive allosteric modulator of MrgX1. ChemMedChem 10:57-61
Schreiber, Stuart L; Kotz, Joanne D; Li, Min et al. (2015) Advancing Biological Understanding and Therapeutics Discovery with Small-Molecule Probes. Cell 161:1252-65
Zhu, Yingmin; Lu, Yungang; Qu, Chunrong et al. (2015) Identification and optimization of 2-aminobenzimidazole derivatives as novel inhibitors of TRPC4 and TRPC5 channels. Br J Pharmacol 172:3495-509

Showing the most recent 10 out of 60 publications