Novel Screen Methodologies for Identification
of New Microbial Metabolites
with Pharmacological Activity
D.C. Hill, S.K. Wrigley and L.J. Nisbet
Xenova Ltd, 240 Bath Road, Slough, Berkshire SL1 4EF, UK
1 Introduction .............................................
75
1.1 The Value of Microbial Chemical Diversity ........................
75
1.2 Demands of Assays Designed for Testing Microbial Samples ..............
75
1.3 Overview of General Assay Categories ...........................
77
2 Cell-Based Assays ..........................................
78
2.1 Inflammatory Disease .....................................
78
2.1.1 Immunomodulation ...................................
78
2.1.2 Immunosuppression ..................................
78
2.1.3 Inhibition of Cell Adhesion ..............................
80
2.1.4 Macrophage Activation ................................
81
2.1.5 Other Screen Methodologies and Targets ......................
82
2.2 Cancer ..............................................
82
2.2.1 Multidrug Resistance (MDR) .............................
82
2.2.2 Cell Cycle Inhibitors ..................................
83
2.2.3 Other Screen Methodologies and Targets ......................
83
2.3 Cardiovascular Disease ....................................
84
2.3.1 Inhibition of Platelet Aggregation ..........................
84
2.3.2 Angiogenesis Inhibitors ................................
85
2.4 CNS Disease ..........................................
86
2.4.1 Nerve Growth Factor (NGF) Mimics ........................
86
3 Receptor Binding Assays .....................................
87
3.1 Inflammatory Disease .....................................
87
3.1.1 Leukotriene B4 (LTB4) Binding Inhibitors .....................
87
3.1.2 CD4 Binding Inhibitors ................................
88
3.2 Cancer ..............................................
89
3.2.1 Hormone Binding Inhibitors .............................
89
3.3 Cardiovascular Disease ....................................
91
3.3.1 Inhibition of Atrial Natriuretic Factor (ANF) Binding ..............
91
3.3.2 Endothelin (ET) Binding Inhibitors .........................
91
3.4 CNS Disease ..........................................
93
3.4.1 Inhibition of Tachykinin Binding ...........................
93
3.4.2 GABAA-Benzodiazepine Receptor Binding Inhibitors ...............
95
4 Enzyme Assays ...........................................
95
4.1 Inflammatory Disease .....................................
96
4.1.1 Sugar Metabolism Inhibitors .............................
96
4.1.2 Inhibition of Lipid Metabolism ............................
97
4.1.3 Human Leukocyte Elastase Inhibitors ........................
98
4.2 Cancer ..............................................
98
4.2.1 Inhibition of Cell Signalling Enzymes ........................
98
4.2.2 Compounds Inhibiting DNA-Dependent Enzymes ................
100
4.2.3 Inhibition of Glandular Estrogen Biosynthesis ...................
102
4.2.4 Testosterone Metabolism Inhibitors .........................
102
4.2.5 Other Screen Methodologies and Targets ......................
102
Advances in Biochemical Engineering/
Biotechnology, Vol. 59
Managing Editor: T. Scheper
9 Springer-Verlag Berlin Heidelberg 1998