In-house screening

In order to understand the potency of a given molecule, project scientists must first understand the nature of the measurement used to generate the potency value. If the molecule in question is from a literature report, there may be no in-house data to examine, and in that case the synthesis of the compound and the development of an assay usually becomes a critical first step to understanding the project landscape at that point. More commonly, however, the compound in question has been identified in some type of in-house screening process. These can take many forms, but they can broadly be grouped into two major categories ... 

Research projects in pharmaceutical industry that are in an early phase need bioactive chemotypes as potential lead structures for optimization. Hits with a medium or even weak activity can serve as leads if the overall profile looks attractive. HTS of the in-house compound libraries is the most common source of these lead structures. If information about the 3D structure of the target and/or about bioactive ligand(s) is available, virtual screening can be used to add further active chemotypes either from the existing compounds, for example, from vendor catalogues, or from the virtual chemical space, for example, from virtual combinatorial libraries. Virtual screening can also be used to select a subset from the in-house screening collection if a full HTS is not possible due to cost or time limitations. 

In contrast, biotech companies with only a small or even without an in-house screening pool depend on virtual screening techniques to access potentially active compounds from external sources. The same is true for academic groups that in most cases neither have access to an in-house compound library nor have access to HTS facilities. 

Attic Ventilators- In houses, screened openings provided to ventilate an attic space. 

In conventional approaches, databases of enimierated molecules are searched. External vendor databases consist of 10—20 million compoimds, which are usually physically available [9]. VS and purchasing the virtual hits from the external vendors dramatically expands the in-house screening pools that at maximum contain only a few miUion compounds. Here at Boehringer Ingelheim on a routine basis, we search in external vendor databases. Thus, we are complementing... 

Virtual screening assists the selection of compounds for screening in-house libraries and compounds from external suppliers. Two different strategies can be applied ... 

Muscarinic M3 Receptor. A pharmacophore model was derived from known M3 receptor antagonists, using the program DISCO, and 3D searching was performed by Unity 3D in the Astra Charnwood in-house compound repository and the databases of several commercial suppliers. The 172 compounds that fitted the pharmacophore were screened for their M3-antagonistic potency. Several compounds with micromolar and even submicromolar activities resulted, for example, compound 13 (A50 M3 antagonism 0.2pM pA2 = 6.67 Fig. 16.2) [85],... 

NMR 3D structure of the undecapeptide U-II generated a ligand pharmacophore hypothesis that served as query for the virtual screening of the Aventis in-house compound repository. Active leads from six different chemical classes could be identihed by the 3D search, for example, compound 17 (ECso = 400nM Fig. 16.2) [91]. 

Inosine 5 -Monophosphate Dehydrogenase. A series of 21 known inosine 5 -monophosphate dehydrogenase (IMPDH) inhibitors was used to validate a virtual screening protocol. By application of a molecular weight filter (80 < MW < 400), 3425 compounds were extracted from an in-house reagent inventory system. Docking of these compounds into a substrate-IMPDH complex 3D structure was performed with the program FlexX three... 

SB-366791 (18) emerged from screening an in-house library as a potent competitive inhibitor of both hTRPVl and rTRPVl, endowed with superior target selectivity compared to capsazepine [84]. Structure-activity relationships of SB-366791 remain to be reported. 

Catalysts used in the trickle bed reactor were supplied by Engelhard Chemical Catalyst Group prepared industrially to match in-house prepared catalysts used in our initial screening. 

For a long time there has been private, in-house quality research, especially in the biodynamic sector and by some larger organic traders and processors. These vary from crystallisation techniques to broad screen residue analyses of raw materials. These in-house quality management schemes are not standard they depend on how seriously the companies take their responsibility towards their clients and/or want to avoid surprises by the food authorities. 

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