Compound registration systems

Obviously a compound registration system is already a fundamental part of the informatics infrastructure for any pharmaceutical company. However, there is a powerful efficiency gain in not having scientists input information twice into different systems the reaction information into the ELN and then the product molecules into the registration system. One would rather have a mechanism of pushing the product molecule information from the ELN to the registration system. The obvious corollary to this is to have the ability to retrieve compound information from the registration system and have it automatically entered into the ELN—an example would be for the scientist to... 

As one of the indispensable software tools, the compound registration system provides a mechanism for the medicinal chemist to capture chemical structure information as well as analytical and other data in a database. We mention two of the systems below. 

In a compound registration system, compound data can be imported from data files such as SD File, XML File, or Mobile. Alternatively, data can be entered from the presentation layer using a structure drawing package such as ISISDraw or ChemDraw. These data, once imported to the system, need to be bound to the domain objects in order for the system to process them efficiently. To support a variety of data sources, a Data Binder API is needed to decouple the system from specific format of input data and make it easily extensible to support other data input formats down the road. Figure 12.17 is the class diagram of the Data Binder API. 

One critical task of any compound registration system is to make sure molecular structures are compliant with chemistry conventions. This ensures consistent representations of molecular structures in the database so that structure searches can find, and only find, the right compounds. Although different organizations may have slightly different conventions, the following ones are some of the most common that the Chemistry Intelligence API takes care of. 

Chemical Compound Registry and Business Rules 14.3.2.1 Function of Compound Registration System... 

In some cases, single component representation is unsuitable. Figure 14.4 shows a simple sequence of structure standardization executed by a compound registration system including structure correction of the benzothiadiazole, salt/addend stripping and neutralization to depict the canonical parent structure representation. Any alternative salt form or structure representation of this compound will be standardized into the same parent structure and thus recognized as identical (at that level). 

Every chemical company or research organization has a collection of compounds of interest. These may be compounds synthesized by chemists employed at the company, compounds purchased from chemical vendors, compounds on which research has been carried out, or any other collection of compounds. When a new compound becomes of interest, it is important to know whether that compound has already been entered into the system, or a new entry needs to be made. The use of canonical SMILES as a unique name for each structure makes this an easy task. One essential table in a compound registration system is a table of unique structures. Such a table could be defined as follows. 

Figure 13.2 Entity relationship diagram for schema containing tables for a compound registration system.

System makes sure all required data are entered (see Compound Registration Required and Optional Data Supplement). System performs uniqueness check against the database (see Uniqueness Check Business Rules Supplement). If the structure is unique, System registers the compound with a new sample identifier (see Sample Identifier Generation Rules Supplement). If it is not unique, System displays the compound to be registered and the hit compounds from uniqueness search and prompts die Chemist to resolve (see Resolve Compounds Use Case Spec). 

To increase productivity, a registration system should be able to register a compound library as a single transaction. Usually a compound library consists of a group of compounds that are synthesized using parallel synthesis, combinatorial chemistry, or compounds that are acquired from commercial or academic sources. From the compound registration perspective, a library can also be a group of compounds that share some common attributes such as a research project they are synthesized for, the chemist who synthesized them, the creation date, and the notebook information. 

The above entity dictionary module provides fast, in-memory access of most frequently accessed data for the compound registration process while keeping the in-memory cache up-to-date. In a multitiered system, controlling network traffic is critical to its speed and user experience. The above design eliminates the need of querying the database every time a piece of data is asked for, and since the system can use the cached dictionaries to display only the valid entities to the user, it also reduces human errors. 

Also, I thank my other colleagues at Merck John Simon, Dr. Yao Wang, Dr. Annie Samuel, Dr. Jay Mehta, James Goggin, Andrew Ferguson, and Marianne Malloy. They were all part of the Merck Chemical Registration System Project Team, and many of them shared invaluable knowledge about compound data management with me. 

As mentioned above, one can purchase compounds already plated in microtiter plates from any of several vendors for 10-20 per mg of sample. The compounds are distributed on 96-well plates (see Fig. 1), allowing blank columns for positive (reference compound) and/or negative (solvent) controls. The plates are now frequently shipped with electronic plate maps on computer disks. These plate maps contain relevant information on structure and vendor ID numbers. Many pharma sites are now spending the time to solvate and distribute their existing compound libraries on microtiter plates. The compound ID numbers and plate maps can easily be imported into virtually any compound registration software system. This information can be linked to data analysis packages (see below) to provide a means of integrating structure and activity data. 

MDL SCREEN MDL Information Systems (San Leandro, CA, U.S.A.) Oracle -based accessible multi-platform > S100K Compound registration, assay assignment, data analysis, data storage and retrieval, easy interface with chemical structure and Oracle-based infrastructure, available on multiple desktop platforms More expensive and very hard to customize... 

The chemical business rules of a compound registration solution define the individual identities of chemical structure representations in order to meaningfully assign a unique corporate ID to each unique structure. After applying these rules, standardized parent structures are stored in a main structure table. The (structure) records from the original compound library data file entering the system are saved into a batch table on which each batch entry is associated with its unique parent structure. All data relating to the physical compound sample remain uniquely associated with this batch entry and thus are also associated with one unique parent structure. 

A number of companies, such as Pfizer, have instituted an organisation-wide rule in their registration systems in which compounds are flagged automatically if two or more of these parameters are out of range from the rule of five , alerting them to the fact that poor absorption or permeability is possible with such compounds.14... 

Many groups register only the compounds from an HTOS experiment that are bioactive. After the samples are fully characterized, they are registered in a traditional manner. Because the hit rate from HTS is typically less than 1%, this method does not seriously overload in-place registration systems. The disadvantage to this method is that the information that a compound has been synthesized is lost. Not having access to that information can result in the repetition of experiments. 

A particular complication for registration systems is the requirement to register compounds whose structure is not completely known. For example, a chemist... 

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