Combinatorial chemistry and high-throughput screening in drug discovery: different strategies and formats.

Molecular diversity ·Vol. 5 ·No. 2 ·2000-00-00 ·Pages 75-89

Seneci P, Miertus S

Abstract

Different strategies for the discovery of novel leads interacting with therapeutically relevant targets are thoroughly presented and discussed, using also three recent examples. Emphasis is given to approaches which do not require extensive resources and budgets, but rather prove how cleverness and creativity can provide active compounds in drug discovery.

MeSH Terms

Combinatorial Chemistry Techniques Drug Design Drug Evaluation, Preclinical/methods,trends Models, Chemical Peptide Library

Chemicals

Peptide Library

Authors & Affiliations

2 authors, click to expand affiliations / ORCID

Seneci P

Nucleotide Analog Pharma AG, Landsbergerstrasse 50, D-80339 München, Germany. pierfausto.seneci@napag.de

Miertus S

References (25)

25 references, click to expand

Structure and inhibition of plasmepsin II, a hemoglobin-degrading enzyme from Plasmodium falciparum.
Proc Natl Acad Sci U S A. 1996 Sep 17;93(19):10034-9 PMID: 8816746
Potent, low-molecular-weight non-peptide inhibitors of malarial aspartyl protease plasmepsin II.
J Med Chem. 1999 Apr 22;42(8):1428-40 PMID: 10212129
Cloning, expression and pharmacological characterization of a human glutamate receptor: hGluR4.
Receptors Channels. 1995;3(1):21-31 PMID: 8589990
A drug that facilitates glutamatergic transmission reduces exploratory activity and improves performance in a learning-dependent task.
Synapse. 1993 Dec;15(4):326-9 PMID: 8153879
Facilitation of glutamate receptors enhances memory.
Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):777-81 PMID: 8290599
Modulation of AMPA/kainate receptors by analogues of diazoxide and cyclothiazide in thin slices of rat hippocampus.
Receptors Channels. 1993;1(4):267-78 PMID: 7915948
High-throughput screening: new technology for the 21st century.
Curr Opin Chem Biol. 2000 Aug;4(4):445-51 PMID: 10959774
Exploiting chemical libraries, structure, and genomics in the search for kinase inhibitors.
Science. 1998 Jul 24;281(5376):533-8 PMID: 9677190
Benzothiadiazides inhibit rapid glutamate receptor desensitization and enhance glutamatergic synaptic currents.
J Neurosci. 1993 Sep;13(9):3904-15 PMID: 8103555
Crystal structure of protein farnesyltransferase at 2.25 angstrom resolution.
Science. 1997 Mar 21;275(5307):1800-4 PMID: 9065406
Comprehensive survey of combinatorial library synthesis: 1999.
J Comb Chem. 2000 Sep-Oct;2(5):383-433 PMID: 11029163
Diversity screening versus focussed screening in drug discovery.
Drug Discov Today. 2000 Jul;5(7):286-293 PMID: 10856911
High-diversity combinatorial libraries.
Curr Opin Chem Biol. 2000 Jun;4(3):295-302 PMID: 10826979
Piracetam and other structurally related nootropics.
Brain Res Brain Res Rev. 1994 May;19(2):180-222 PMID: 8061686
New 4-point pharmacophore method for molecular similarity and diversity applications: overview of the method and applications, including a novel approach to the design of combinatorial libraries containing privileged substructures.
J Med Chem. 1999 Aug 26;42(17):3251-64 PMID: 10464012
Expedient method for the solid-phase synthesis of aspartic acid protease inhibitors directed toward the generation of libraries.
J Med Chem. 1995 Apr 28;38(9):1427-30 PMID: 7739000
(+)-4-[2-[4-(8-Chloro-3,10-dibromo-6,11-dihydro-5H-benzo[5, 6]cyclohepta[1,2-b]- pyridin-11(R)-yl)-1-piperidinyl]-2-oxo-ethyl]-1-piperidinecarboxamid e (SCH-66336): a very potent farnesyl protein transferase inhibitor as a novel antitumor agent.
J Med Chem. 1998 Nov 19;41(24):4890-902 PMID: 9822558
7-Chloro-3-methyl-3,4-dihydro-2H-1,2,4-benzothiadiazine S,S-dioxide (IDRA 21), a congener of aniracetam, potently abates pharmacologically induced cognitive impairments in patas monkeys.
Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7667-71 PMID: 7644474
Biarylpropylsulfonamides as novel, potent potentiators of 2-amino-3- (5-methyl-3-hydroxyisoxazol-4-yl)- propanoic acid (AMPA) receptors.
J Med Chem. 2000 Nov 16;43(23):4354-8 PMID: 11087558
Aniracetam. An overview of its pharmacodynamic and pharmacokinetic properties, and a review of its therapeutic potential in senile cognitive disorders.
Drugs Aging. 1994 Mar;4(3):257-73 PMID: 8199398
Successful virtual screening of a chemical database for farnesyltransferase inhibitor leads.
J Med Chem. 2000 Feb 10;43(3):401-8 PMID: 10669567
Structure-based design and combinatorial chemistry yield low nanomolar inhibitors of cathepsin D.
Chem Biol. 1997 Apr;4(4):297-307 PMID: 9195867
Evidence that a positive modulator of AMPA-type glutamate receptors improves delayed recall in aged humans.
Exp Neurol. 1997 May;145(1):89-92 PMID: 9184112
Psychological effects of a drug that facilitates brain AMPA receptors.
Int Clin Psychopharmacol. 1996 Mar;11(1):13-9 PMID: 8732309
Syntheses and absolute structures of novel protein farnesyltransferase inhibitors, kurasoins A and B.
J Antibiot (Tokyo). 1997 May;50(5):453-5 PMID: 9207919

Article Info

Journal

Molecular diversity

Abbr.

Mol Divers

ISSN

1381-1991

DOI

10.1023/a:1013824317218

pierfausto.seneci@napag.de

Published

2000-00-00

Pages

75-89

Language

English

Region

Netherlands

NLM ID

9516534

Subset

External Links

PubMed source DOI: 10.1023/a:1013824317218 View journal details

Analysis Services

Combinatorial chemistry and high-throughput screening in drug discovery: different strategies and formats.

Contact

WeChat Official Account