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  and acceleration of the onset of neurodegenerative disease . The compounds' toxicity  and multiple specific binding targets in the mammalian brain  has made them less attractive as drug leads. ..more
Anesthetic development has remained a largely empirical process. There are growing concerns about the cognitive effects of known general anesthetics  and acceleration of the onset of neurodegenerative disease . The compounds' toxicity  and multiple specific binding targets in the mammalian brain  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 , .
This project is currently ongoing. Additional details of follow-up assays and results will be summarized here in future updates.
 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.
 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.
 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.
 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.
 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.
 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
Please see related BioAssays for all protocols relevant to this probe development project: 2323
Compound ranking comments will be added here as small molecule probes are developed and are annotated with bioassays in PubChem.
Categorized Comment - additional comments and annotations
From MLP Probe Report:
Probe count: 1
MLP Probe ML# for probe 1: ML306
PubChem Substance ID (SID) for probe 1: 134419032
PubChem Compound ID (CID) for probe 1: 5070704
Probe type for probe 1: Modulator
IC50/EC50 (nM) for probe 1: 3040
Target for probe 1: Apoferritin (gi: 254220970)
Disease relevance for probe 1: Surgery
Anti-target for probe 1: In Vivo Tadpole Toxicity
Fold selectivity for probe 1: >90
NCBI Book chapter link for probe 1: http://www.ncbi.nlm.nih.gov/books/NBK153223/ (ID: 3046460)
Grant number for probe 1: MH084836
NCBI Book chapter title for probe 1: Discovery of Novel General Anesthetics Using Apoferritin as a Surrogate System