Bookmark and Share
BioAssay: AID 2385

Probe Development Summary for Identification of Novel General Anesthetics

Anesthetic development has remained a largely empirical process. There are growing concerns about the cognitive effects of known general anesthetics [1] and acceleration of the onset of neurodegenerative disease [2]. The compounds' toxicity [3] and multiple specific binding targets in the mammalian brain [4] has made them less attractive as drug leads. ..more
_
   
AID: 2385
Data Source: NCGC (APOF100)
BioAssay Type: Summary, Candidate Probes/Leads with Supporting Evidence
Depositor Category: NIH Molecular Libraries Probe Production Network
Deposit Date: 2010-02-19
Target
Sequence: Chain A, Horse Spleen Apoferritin
Description ..   
Protein Family: Ferritin iron storage proteins

Related Protein 3D Structures     More BioActivity Data..
Depositor Specified Assays
AIDNameTypeComment
2323qHTS Validation Assay for Identification of Novel General AnestheticsconfirmatoryqHTS Validation Assay for Identification of Novel General Anesthetics
489008Confirmation Assay for Identification of Novel General Anestheticsconfirmatory
624098Assay for General Anesthetic Phenotype in Xenopus Tadpolesscreening
624122Isothermal Titration Calorimetry Based Assay for Measurement of Binding Affinity to Apoferritinconfirmatory
485281qHTS Assay for Identification of Novel General Anestheticsconfirmatory
Description:
Anesthetic development has remained a largely empirical process. There are growing concerns about the cognitive effects of known general anesthetics [1] and acceleration of the onset of neurodegenerative disease [2]. The compounds' toxicity [3] and multiple specific binding targets in the mammalian brain [4] has made them less attractive as drug leads.

In the primary screen for this project, a GABAergic mimetic model system, apoferritin and a profluorescent 1-aminoanthracene ligand (1-AMA), is used to construct a competitive binding assay for identification of novel general anesthetics [5], [6].

This project is currently ongoing. Additional details of follow-up assays and results will be summarized here in future updates.

References:

[1] S.L. Bianchi, T. Tran, C. Liu, S. Lin, Y. Li, J.M. Keller, R.G. Eckenhoff, and M.F. Eckenhoff, Brain and behavior changes in 12-month-old Tg2576 and nontransgenic mice exposed to anesthetics. Neurobiol Aging 29 (2008) 1002-10.

[2] Z. Xie, Y. Dong, U. Maeda, R.D. Moir, W. Xia, D.J. Culley, G. Crosby, and R.E. Tanzi, The inhalation anesthetic isoflurane induces a vicious cycle of apoptosis and amyloid beta-protein accumulation. J Neurosci 27 (2007) 1247-54.

[3] P. Honegger, and J.M. Matthieu, Selective toxicity of the general anesthetic propofol for GABAergic neurons in rat brain cell cultures. J Neurosci Res 45 (1996) 631-6.

[4] M.F. Eckenhoff, K. Chan, and R.G. Eckenhoff, Multiple specific binding targets for inhaled anesthetics in the mammalian brain. J Pharmacol Exp Ther 300 (2002) 172-9.

[5] C.A. Butts, J. Xi, G. Brannigan, A.A. Saad, S.P. Venkatachalan, R.A. Pearce, M.L. Klein, R.G. Eckenhoff, and I.J. Dmochowski, Identification of a fluorescent general anesthetic, 1-aminoanthracene. Proc Natl Acad Sci U S A 106 (2009) 6501-6.

[6] W.A. Lea, J. Xi, A. Jadhav, L. Lu, C.P. Austin, A. Simeonov, and R.G. Eckenhoff, A high-throughput approach for identification of novel general anesthetics. PLoS One 4 (2009) e7150.

Source: NIH Chemical Genomics Center [NCGC]
Assay Submitter: Roderic Eckenhoff, University of Pennsylvania
Screening Center PI: Christopher P. Austin, NIH
Probe Development: NIH Chemical Genomics Center [NCGC]
NIH Grant Number: MH084836-01
Protocol
Please see related BioAssays for all protocols relevant to this probe development project: 2323
Comment
Compound ranking comments will be added here as small molecule probes are developed and are annotated with bioassays in PubChem.
Additional Information
Grant Number: MH084836-01

PageFrom: